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Li N, Zhang Y, Zhang Q, Jin H, Han M, Guo J, Zhang Y. Machine learning reveals glycolytic key gene in gastric cancer prognosis. Sci Rep 2025; 15:8688. [PMID: 40082583 PMCID: PMC11906761 DOI: 10.1038/s41598-025-93512-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2024] [Accepted: 03/07/2025] [Indexed: 03/16/2025] Open
Abstract
Glycolysis is recognized as a central metabolic pathway in the neoplastic evolution of gastric cancer, exerting profound effects on the tumor microenvironment and the neoplastic growth trajectory. However, the identification of key glycolytic genes that significantly affect gastric cancer prognosis remains underexplored. In this work, five machine-learning algorithms were used to elucidate the intimate association between the glycolysis-associated gene phosphofructokinase fructose-bisphosphate 3 (PFKFB3) and the prognosis of gastric cancer patients. Validation across multiple independent datasets confirmed the prognostic significance of PFKFB3. Further, we delved into the functional implications of PFKFB3 in modulating immune responses and biological processes within gastric cancer patients, as well as its broader relevance across multiple cancer types. Results underscore the potential of PFKFB3 as a prognostic biomarker and therapeutic target in gastric cancer. Our project can be found at https://github.com/PiPiNam/ML-GCP .
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Affiliation(s)
- Nan Li
- China Academy of Electronics and Information Technology, National Engineering Research Center for Public Safety Risk Perception and Control by Big Data (RPP), Beijing, China
| | - Yuzhe Zhang
- The First Laboratory of Cancer Institute, The First Hospital of China Medical University, Shenyang, China
| | - Qianyue Zhang
- China Academy of Electronics and Information Technology, National Engineering Research Center for Public Safety Risk Perception and Control by Big Data (RPP), Beijing, China
| | - Hao Jin
- China Academy of Electronics and Information Technology, National Engineering Research Center for Public Safety Risk Perception and Control by Big Data (RPP), Beijing, China
| | - Mengfei Han
- China Academy of Electronics and Information Technology, National Engineering Research Center for Public Safety Risk Perception and Control by Big Data (RPP), Beijing, China
| | - Junhan Guo
- Center for Reproductive Medicine, Henan Key Laboratory of Reproduction and Genetics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Ye Zhang
- The First Laboratory of Cancer Institute, The First Hospital of China Medical University, Shenyang, China.
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Chen D, Zhang P, Gong L, Wei H, Yu G, Zhang T, Bai C. Integrative analysis of single-cell and bulk RNA sequencing reveals the oncogenic role of ANXA5 in gastric cancer and its association with drug resistance. Front Immunol 2025; 16:1562395. [PMID: 40124374 PMCID: PMC11925758 DOI: 10.3389/fimmu.2025.1562395] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2025] [Accepted: 02/18/2025] [Indexed: 03/25/2025] Open
Abstract
Background Gastric cancer (GC) remains a leading cause of cancer-related mortality, with over one million new cases and 769,000 deaths reported in 2020. Despite advancements in chemotherapy, surgery, and targeted therapies, delayed diagnosis due to overlooked early symptoms leads to poor prognosis. Methods We integrated bulk RNA sequencing and single-cell RNA sequencing datasets from TCGA, GEO, and OMIX001073, employing normalization, batch effect correction, and dimensionality reduction methods to identify key cell populations associated with GC invasion and epithelial-mesenchymal transition (EMT), as well as analyze the tumor immune microenvironment. Results Our analysis identified the MUC5AC+ malignant epithelial cell cluster as a significant player in GC invasion and EMT. Cluster 1, representing this cell population, exhibited higher invasion and EMT scores compared to other clusters. Survival analysis showed that high abundance in cluster 0 correlated with improved survival rates (P=0.012), whereas cluster 1 was associated with poorer outcomes (P=0.045). A prognostic model highlighted ANXA5 and GABARAPL2 as two critical genes upregulated in GC tumors. High-risk patients demonstrated increased immune cell infiltration and worse prognosic. Analysis of tumor mutation burden (TMB) indicated that patients with low TMB in the high-risk group had the worst prognosis. Wet-lab validation experiments confirmed the oncogenic role of ANXA5, showing its facilitation of cell proliferation, invasion, and migration while suppressing apoptosis. Conclusion This study offers novel insights into the subpopulations of malignant epithelial cells in GC and their roles in tumor progression. It provides a prognostic model and potential therapeutic targets to combat GC, contributing crucial understanding to the fundamental mechanisms of drug resistance in gastrointestinal cancers.
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Affiliation(s)
- Denggang Chen
- Department of General Surgery, Taihe Hospital, Hubei University of Medicine, Shiyan, China
| | - Peng Zhang
- Department of General Surgery, Taihe Hospital, Hubei University of Medicine, Shiyan, China
- College of Life Sciences, South-Central Minzu University, Wuhan, China
| | - Li Gong
- Department of Endocrinology, Taihe Hospital, Hubei University of Medicine, Shiyan, China
| | - Hailang Wei
- Department of General Surgery, Taihe Hospital, Hubei University of Medicine, Shiyan, China
| | - Guanghui Yu
- College of Life Sciences, South-Central Minzu University, Wuhan, China
| | - Tingting Zhang
- Department of Clinical Oncology, Taihe Hospital, Hubei University of Medicine, Shiyan, China
| | - Chen Bai
- Department of General Surgery, Taihe Hospital, Hubei University of Medicine, Shiyan, China
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Maruyama S, Imamura Y, Toihata T, Haraguchi I, Takamatsu M, Yamashita M, Nakashima Y, Oki E, Taguchi K, Yamamoto M, Mine S, Okamura A, Kanamori J, Nunobe S, Sano T, Kitano S, Noda T, Watanabe M. FOXP3+/CD8+ ratio associated with aggressive behavior in RUNX3-methylated diffuse esophagogastric junction tumor. Cancer Sci 2025; 116:178-191. [PMID: 39440906 PMCID: PMC11711055 DOI: 10.1111/cas.16373] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2024] [Revised: 09/21/2024] [Accepted: 10/03/2024] [Indexed: 10/25/2024] Open
Abstract
The tumor immune microenvironment is increasingly becoming a key consideration in developing treatment regimens for aggressive cancers, with evidence that regulatory T cells (Tregs) attenuate the antitumor response by interrupting cytotoxic T cells (CD8+). Here, we hypothesized the prognostic relevance of the proportions of Tregs (marked by forkhead box protein 3 [FOXP3]) and CD8+ cells in diffuse, non-Epstein-Barr virus (EBV)/non-microsatellite instability (MSI)-high gastroesophageal adenocarcinomas (GEAs), which are clinically characterized as more aggressive, immunologically inactive tumors as compared with their intestinal counterparts. Cell-count ratios of FOXP3+/CD8+ expression were calculated at the intratumoral region and invasive margin discretely on digital images from 303 chemo-naive non-EBV/non-MSI-high esophagogastric junction (EGJ) adenocarcinomas. A significant modifying prognostic effect of tumor histology was observed between 5-year EGJ cancer-specific survival and the FOXP3+/CD8+ ratio at the invasive margin in pStage I-III tumors (p for interaction = 0.022; hazard ratio [HR] = 8.47 and 95% confidence interval [CI], 2.04-35.19 for high ratio [vs. low] for diffuse; HR = 1.57 and 95% CI, 0.88-2.83 for high ratio [vs. low] for intestinal). A high FOXP3+/CD8+ ratio at the invasive margin was associated with RUNX3 methylation (p = 0.035) and poor prognosis in RUNX3-methylated diffuse histological subtype (5-year EGJ cancer-specific survival, 52.3% for high and 100% for low, p = 0.015). Multiomics data from The Cancer Genome Atlas linked CCL28 with RUNX3-suppressed diffuse histological subtypes of non-EBV/non-MSI-high GEA. Our data suggest that a high FOXP3+/CD8+ ratio at the invasive margin might indicate tumor immune escape via CCL28, particularly in the RUNX3-methylated diffuse histological subtype.
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Affiliation(s)
- Suguru Maruyama
- Department of Gastroenterological Surgery, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Yu Imamura
- Department of Gastroenterological Surgery, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Tasuku Toihata
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Ikumi Haraguchi
- Cancer Precision Medicine Center, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Manabu Takamatsu
- Department of Pathology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Makiko Yamashita
- Advanced Medical Development Center, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Yuichiro Nakashima
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Eiji Oki
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Kenichi Taguchi
- Department of Pathology, Kyushu Cancer Center, National Hospital Organization, Fukuoka, Japan
| | - Manabu Yamamoto
- Department of Gastroenterological Surgery, Kyushu Cancer Center, National Hospital Organization, Fukuoka, Japan
| | - Shinji Mine
- Department of Esophageal and Gastroenterological Surgery, Juntendo University Hospital, Tokyo, Japan
| | - Akihiko Okamura
- Department of Gastroenterological Surgery, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Jun Kanamori
- Department of Gastroenterological Surgery, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Souya Nunobe
- Department of Gastroenterological Surgery, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Takeshi Sano
- Department of Gastroenterological Surgery, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Shigehisa Kitano
- Advanced Medical Development Center, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Tetsuo Noda
- Cancer Precision Medicine Center, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Masayuki Watanabe
- Department of Gastroenterological Surgery, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
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Charach L, Perets TT, Gingold-Belfer R, Huta Y, Ashorov O, Levi Z, Dickman R, Boltin D. Comparison of Four Tests for the Diagnosis of Helicobacter pylori Infection. Healthcare (Basel) 2024; 12:1479. [PMID: 39120182 PMCID: PMC11312091 DOI: 10.3390/healthcare12151479] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2024] [Revised: 07/22/2024] [Accepted: 07/24/2024] [Indexed: 08/10/2024] Open
Abstract
BACKGROUND Due to lower operational costs, health maintenance organizations (HMOs) may prioritize Helicobacter pylori stool antigen testing (HpStAg) for the non-invasive diagnosis of H. pylori infection over 13C-urea breath tests (13C-UBTs). The aim of our study was to compare the accuracy of the diagnostic tests for H. pylori. METHODS We performed histology, rapid urease test (RUT), 13C-UBT and HpStAg on consecutive patients referred for gastroscopy. Monoclonal stool antigen test was performed using the LIAISON Meridian chemiluminescent immunoassay. Histology was examined with hematoxylin and eosin, and additional stains were performed at the pathologist's discretion. For the assessment of 13C-UBT, we compared concordant histology and RUT. HpStAg was compared to the concordant results of two of the three remaining tests. RESULTS 103 patients were included (36 males (35.0%), age 50.1 ± 18.4 years). The indication for gastroscopy was dyspepsia in 63 (61.2%). Agreement between RUT and histology was 95.9%. For 13C-UBT and HpStAg, respectively, H. pylori positivity was 30% (30/100) and 27.16% (22/81); sensitivity was 97% and 70%; specificity was 100% and 94.4%; accuracy was 98% and 86%; positive predictive value (PPV) was 100% and 86.4%; negative predictive value (NPV) was 93% and 86%. No demographic, clinical, or endoscopic predictors of HpStAg accuracy were identified using logistic regression. CONCLUSIONS 13C-UBT performs better than HpStAg at our institution. When interpreting results, clinicians should consider test limitations.
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Affiliation(s)
- Lior Charach
- Internal Medicine B, Rabin Medical Center, Petah Tikva 49100, Israel;
| | - Tsachi Tsadok Perets
- Gastroenterology Laboratory, Rabin Medical Center, Petah Tikva 49100, Israel; (T.T.P.); (Y.H.); (O.A.)
- Department of Digital Medical Technologies, Holon Institute of Technology, Holon 58444, Israel
| | - Rachel Gingold-Belfer
- Division of Gastroenterology, Rabin Medical Center, Petah Tikva 49100, Israel; (R.G.-B.); (Z.L.); (R.D.)
| | - Yair Huta
- Gastroenterology Laboratory, Rabin Medical Center, Petah Tikva 49100, Israel; (T.T.P.); (Y.H.); (O.A.)
| | - Olga Ashorov
- Gastroenterology Laboratory, Rabin Medical Center, Petah Tikva 49100, Israel; (T.T.P.); (Y.H.); (O.A.)
| | - Zohar Levi
- Division of Gastroenterology, Rabin Medical Center, Petah Tikva 49100, Israel; (R.G.-B.); (Z.L.); (R.D.)
| | - Ram Dickman
- Division of Gastroenterology, Rabin Medical Center, Petah Tikva 49100, Israel; (R.G.-B.); (Z.L.); (R.D.)
| | - Doron Boltin
- Division of Gastroenterology, Rabin Medical Center, Petah Tikva 49100, Israel; (R.G.-B.); (Z.L.); (R.D.)
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Zhu DH, Su KK, Ou-Yang XX, Zhang YH, Yu XP, Li ZH, Ahmadi-Nishaboori SS, Li LJ. Mechanisms and clinical landscape of N6-methyladenosine (m6A) RNA modification in gastrointestinal tract cancers. Mol Cell Biochem 2024; 479:1553-1570. [PMID: 38856795 PMCID: PMC11254988 DOI: 10.1007/s11010-024-05040-x] [Citation(s) in RCA: 8] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2024] [Accepted: 05/18/2024] [Indexed: 06/11/2024]
Abstract
Epigenetics encompasses reversible and heritable chemical modifications of non-nuclear DNA sequences, including DNA and RNA methylation, histone modifications, non-coding RNA modifications, and chromatin rearrangements. In addition to well-studied DNA and histone methylation, RNA methylation has emerged as a hot topic in biological sciences over the past decade. N6-methyladenosine (m6A) is the most common and abundant modification in eukaryotic mRNA, affecting all RNA stages, including transcription, translation, and degradation. Advances in high-throughput sequencing technologies made it feasible to identify the chemical basis and biological functions of m6A RNA. Dysregulation of m6A levels and associated modifying proteins can both inhibit and promote cancer, highlighting the importance of the tumor microenvironment in diverse biological processes. Gastrointestinal tract cancers, including gastric, colorectal, and pancreatic cancers, are among the most common and deadly malignancies in humans. Growing evidence suggests a close association between m6A levels and the progression of gastrointestinal tumors. Global m6A modification levels are substantially modified in gastrointestinal tumor tissues and cell lines compared to healthy tissues and cells, possibly influencing various biological behaviors such as tumor cell proliferation, invasion, metastasis, and drug resistance. Exploring the diagnostic and therapeutic potential of m6A-related proteins is critical from a clinical standpoint. Developing more specific and effective m6A modulators offers new options for treating these tumors and deeper insights into gastrointestinal tract cancers.
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Affiliation(s)
- Dan-Hua Zhu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China
| | - Kun-Kai Su
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China
| | - Xiao-Xi Ou-Yang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China
| | - Yan-Hong Zhang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China
| | - Xiao-Peng Yu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China
| | - Zu-Hong Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China
| | | | - Lan-Juan Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.
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Syed RU, Afsar S, Aboshouk NAM, Salem Alanzi S, Abdalla RAH, Khalifa AAS, Enrera JA, Elafandy NM, Abdalla RAH, Ali OHH, Satheesh Kumar G, Alshammari MD. LncRNAs in necroptosis: Deciphering their role in cancer pathogenesis and therapy. Pathol Res Pract 2024; 256:155252. [PMID: 38479121 DOI: 10.1016/j.prp.2024.155252] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2024] [Revised: 03/02/2024] [Accepted: 03/04/2024] [Indexed: 04/14/2024]
Abstract
Necroptosis, a controlled type of cell death that is different from apoptosis, has become a key figure in the aetiology of cancer and offers a possible target for treatment. A growing number of biological activities, including necroptosis, have been linked to long noncoding RNAs (lncRNAs), a varied family of RNA molecules with limited capacity to code for proteins. The complex interactions between LncRNAs and important molecular effectors of necroptosis, including mixed lineage kinase domain-like pseudokinase (MLKL) and receptor-interacting protein kinase 3 (RIPK3), will be investigated. We will explore the many methods that LncRNAs use to affect necroptosis, including protein-protein interactions, transcriptional control, and post-transcriptional modification. Additionally, the deregulation of certain LncRNAs in different forms of cancer will be discussed, highlighting their dual function in influencing necroptotic processes as tumour suppressors and oncogenes. The goal of this study is to thoroughly examine the complex role that LncRNAs play in controlling necroptotic pathways and how that regulation affects the onset and spread of cancer. In the necroptosis for cancer treatment, this review will also provide insight into the possible therapeutic uses of targeting LncRNAs. Techniques utilising LncRNA-based medicines show promise in controlling necroptotic pathways to prevent cancer from spreading and improve the effectiveness of treatment.
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Affiliation(s)
- Rahamat Unissa Syed
- Department of Pharmaceutics, College of Pharmacy, University of Ha'il, Hail 81442, Saudi Arabia.
| | - S Afsar
- Department of Virology, Sri Venkateswara University, Tirupathi, Andhra Pradesh 517502, India.
| | - Nayla Ahmed Mohammed Aboshouk
- Department of Clinical laboratory Sciences, College of Applied Medical Sciences, University of Hail, Hail 81442, Saudi Arabia
| | | | | | - Amna Abakar Suleiman Khalifa
- Department of Clinical laboratory Sciences, College of Applied Medical Sciences, University of Hail, Hail 81442, Saudi Arabia
| | - Jerlyn Apatan Enrera
- Department of Clinical laboratory Sciences, College of Applied Medical Sciences, University of Hail, Hail 81442, Saudi Arabia
| | - Nancy Mohammad Elafandy
- Department of Clinical laboratory Sciences, College of Applied Medical Sciences, University of Hail, Hail 81442, Saudi Arabia
| | - Randa Abdeen Husien Abdalla
- Department of Clinical laboratory Sciences, College of Applied Medical Sciences, University of Hail, Hail 81442, Saudi Arabia
| | - Omar Hafiz Haj Ali
- Department of Clinical laboratory Sciences, College of Applied Medical Sciences, University of Hail, Hail 81442, Saudi Arabia
| | - G Satheesh Kumar
- Department of Pharmaceutical Chemistry, College of Pharmacy, Seven Hills College of Pharmacy, Venkataramapuram, Tirupati, India
| | - Maali D Alshammari
- Department of Pharmaceutical Chemistry, College of Pharmacy, University of Hail, Hail 81442, Saudi Arabia
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Kim SH, Kim KA, Joo MK, Lee H, Chung JW, Yun SC, Kim ST. Prospective Evaluation of a New Liquid-Type Rapid Urease Test Kit for Diagnosis of Helicobacter pylori. Diagnostics (Basel) 2024; 14:700. [PMID: 38611613 PMCID: PMC11011464 DOI: 10.3390/diagnostics14070700] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2024] [Revised: 03/25/2024] [Accepted: 03/25/2024] [Indexed: 04/14/2024] Open
Abstract
BACKGROUND/AIMS Rapid and accurate diagnostic tools are essential for the timely recognition of Helicobacter pylori (H. pylori) in clinical practice. The rapid urease test (RUT) is a comparatively accurate and time-saving method recommended as a first-line diagnostic test. The primary objective of conducting the RUT is to obtain rapid results, thus enabling the initiation of an eradication therapy based on clarithromycin resistance testing. This study aimed to assess the reaction time and accuracy of a new liquid-type RUT. METHOD In this prospective study, consecutive dyspeptic or check-up patients referred to our clinic for endoscopy were assessed to evaluate the rapidity and accuracy of a novel liquid-type RUT (Helicotest®, WON Medical, Bucheon, Republic of Korea) compared with another commercial RUT kit (HP kit, Chong Kun Dang, Seoul, Republic of Korea) and a real-time quantitative PCR-based assay (Seeplex® H.pylori-ClaR Detection, Seegene, Republic of Korea). RUTs were analyzed at 10 min, 30 min, 60 min, and 120 min. RESULTS Among the 177 enrolled patients, 38.6% were infected with H. pylori. The positivity rates of the liquid-type RUT were 26.1, 35.8, 39.2%, and 41.5% at 10, 30, 60, and 120 min, respectively. When compared with the HP kit test, the time needed to confirm positivity was significantly reduced by 28.6 min (95% CI, 16.60-39.73, p < 0.0001). Helicotest® had a greater accuracy (96.02 ± 1.47), sensitivity (98.53 ± 1.46) and NPV (99.03 ± 0.97) compared to the HP kit. CONCLUSIONS Compared to the commonly used RUT, the new liquid-type RUT presented faster and reliable results. Such findings could improve H. pylori treatment outcomes, particularly in outpatient clinical settings.
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Affiliation(s)
- Seung Han Kim
- Department of Gastroenterology, Korea University Guro Hospital, Seoul 08308, Republic of Korea; (S.H.K.); (M.K.J.)
| | - Kyeong Ah Kim
- Department of Internal Medicine, Gachon University Gil Medical Center, Incheon 21565, Republic of Korea; (K.A.K.); (H.L.)
| | - Moon Kyung Joo
- Department of Gastroenterology, Korea University Guro Hospital, Seoul 08308, Republic of Korea; (S.H.K.); (M.K.J.)
| | - Hannah Lee
- Department of Internal Medicine, Gachon University Gil Medical Center, Incheon 21565, Republic of Korea; (K.A.K.); (H.L.)
| | - Jun-Won Chung
- Department of Internal Medicine, Gachon University Gil Medical Center, Incheon 21565, Republic of Korea; (K.A.K.); (H.L.)
| | - Sung-Cheol Yun
- Department of Clinical Epidemiology and Biostatistics, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, Republic of Korea;
| | - Seon Tae Kim
- Department of Otolaryngology-Head & Neck Surgery, Gachon University Gil Medical Center, Incheon 21565, Republic of Korea;
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Xiang T, Wei Z, Ye C, Liu G. Prognostic impact and immunotherapeutic implications of NETosis-related gene signature in gastric cancer patients. J Cell Mol Med 2024; 28:e18087. [PMID: 38146607 PMCID: PMC10902305 DOI: 10.1111/jcmm.18087] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2023] [Revised: 12/01/2023] [Accepted: 12/11/2023] [Indexed: 12/27/2023] Open
Abstract
The role of NETosis and its related molecules remains unclear in gastric cancer. The data used in this study was directly downloaded from the Cancer Genome Atlas (TCGA) database. All analysis and plots are completed in R software using diverse R packages. In our study, we collected the list of NETosis-related genes from previous publications. Based on the list and expression profile of gastric cancer patients from the TCGA database, we identified the NETosis-related genes significantly correlated with patients survival. Then, CLEC6A, BST1 and TLR7 were identified through LASSO regression and multivariate Cox regression analysis for prognosis model construction. This prognosis model showed great predictive efficiency in both training and validation cohorts. We noticed that the high-risk patients might have a worse survival performance. Next, we explored the biological enrichment difference between high- and low-risk patients and found that many carcinogenic pathways were upregulated in the high-risk patients. Meanwhile, we investigated the genomic instability, mutation burden and immune microenvironment difference between high- and low-risk patients. Moreover, we noticed that low-risk patients were more sensitive to immunotherapy (85.95% vs. 56.22%). High-risk patients were more sensitive to some small molecules compounds like camptothecin_1003, cisplatin_1005, cytarabine_1006, nutlin-3a (-)_1047, gemcitabine_1190, WZ4003_1614, selumetinib_1736 and mitoxantrone_1810. In summary, our study comprehensively explored the role of NETosis-related genes in gastric cancer, which can provide direction for relevant studies.
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Affiliation(s)
- Tian Xiang
- Department of Clinical Laboratory CenterCentral Hospital of Enshi Tujia and Miao Autonomous PrefectureEnshiChina
| | | | - Chen Ye
- Hubei University of MedicineShiyanChina
| | - Gao Liu
- Department of Gastrointestinal SurgeryCentral Hospital of Enshi Tujia and Miao Autonomous PrefectureEnshiChina
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9
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Li J, Chen Z, Li Q, Liu R, Zheng J, Gu Q, Xiang F, Li X, Zhang M, Kang X, Wu R. Study of miRNA and lymphocyte subsets as potential biomarkers for the diagnosis and prognosis of gastric cancer. PeerJ 2024; 12:e16660. [PMID: 38259671 PMCID: PMC10802158 DOI: 10.7717/peerj.16660] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2023] [Accepted: 11/21/2023] [Indexed: 01/24/2024] Open
Abstract
Objective The aim of this study was to identify the expression of miRNA and lymphocyte subsets in the blood of gastric cancer (GC) patients, elucidate their clinical significance in GC, and establish novel biomarkers for the early diagnosis and prognosis of GC. Methods The expression of miRNAs in the serum of GC patients was screened using second-generation sequencing and detected using qRT-PCR. The correlation between miRNA expression and clinicopathological characteristics of GC patients was analyzed, and molecular markers for predicting cancer were identified. Additionally, flow cytometry was used to detect the proportion of lymphocyte subsets in GC patients compared to healthy individuals. The correlations between differential lymphocyte subsets, clinicopathological features of GC patients, and their prognosis were analyzed statistically. Results The study revealed that hsa-miR-1306-5p, hsa-miR-3173-5p, and hsa-miR-296-5p were expressed at lower levels in the blood of GC patients, which is consistent with miRNA-seq findings. The AUC values of hsa-miR-1306-5p, hsa-miR-3173-5p, and hsa-miR-296-5p were found to be effective predictors of GC occurrence. Additionally, hsa-miR-296-5p was found to be negatively correlated with CA724. Furthermore, hsa-miR-1306-5p, hsa-miR-3173-5p, and hsa-miR-296-5p were found to be associated with the stage of the disease and were closely linked to the clinical pathology of GC. The lower the levels of these miRNAs, the greater the clinical stage of the tumor and the worse the prognosis of gastric cancer patients. Finally, the study found that patients with GC had lower absolute numbers of CD3+ T cells, CD4+ T cells, CD8+ T cells, CD19+ B cells, and lymphocytes compared to healthy individuals. The quantity of CD4+ T lymphocytes and the level of the tumor marker CEA were shown to be negatively correlated. The ROC curve and multivariate logistic regression analysis demonstrated that lymphocyte subsets can effectively predict gastric carcinogenesis and prognosis. Conclusion These miRNAs such as hsa-miR-1306-5p, hsa-miR-3173-5p, hsa-miR-296-5p and lymphocyte subsets such as the absolute numbers of CD3+ T cells, CD4+ T cells, CD8+ T cells, CD19+ B cells, lymphocytes are down-regulated in GC and are closely related to the clinicopathological characteristics and prognosis of GC patients. They may serve as new molecular markers for predicting the early diagnosis and prognosis of GC patients.
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Affiliation(s)
- Jinpeng Li
- Department of Laboratory Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Zixi Chen
- Department of Laboratory Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Qian Li
- Department of Laboratory Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Rongrong Liu
- Department of Laboratory Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Jin Zheng
- Department of Laboratory Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Qing Gu
- Department of Laboratory Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Fenfen Xiang
- Department of Laboratory Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Xiaoxiao Li
- Department of Laboratory Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Mengzhe Zhang
- Department of Laboratory Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Xiangdong Kang
- Department of Laboratory Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Rong Wu
- Department of Laboratory Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
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Graziosi L, Natalizi N, Donini A. Rationale in the Use of Adjuvant Chemotherapy in pT3N0M0 Gastric Cancer Resected Patients. Comment on Chen et al. Prognostic Factors and the Role of Adjuvant Chemotherapy in Pathological Node-Negative T3 Gastric Cancer. J. Pers. Med. 2023, 13, 553. J Pers Med 2023; 13:974. [PMID: 37373963 DOI: 10.3390/jpm13060974] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2023] [Accepted: 05/29/2023] [Indexed: 06/29/2023] Open
Abstract
I read with great interest the well-written and well-made study by Yi-Fu Chen et al. recently published in the "Journal of Personalized Medicine" [...].
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Affiliation(s)
- Luigina Graziosi
- Emergency and General Surgery, "Santa Maria della Misericordia" Hospital, University of Perugia, 06129 Perugia, Italy
| | - Nicola Natalizi
- Emergency and General Surgery, "Santa Maria della Misericordia" Hospital, University of Perugia, 06129 Perugia, Italy
| | - Annibale Donini
- Emergency and General Surgery, "Santa Maria della Misericordia" Hospital, University of Perugia, 06129 Perugia, Italy
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11
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Qiu J, Shi W, Zhang J, Gao Q, Feng L, Zhuang Z. Peripheral CD4 +CD25 hiCD127 low regulatory T cells are increased in patients with gastrointestinal cancer. BMC Gastroenterol 2023; 23:168. [PMID: 37210494 DOI: 10.1186/s12876-023-02798-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2022] [Accepted: 05/03/2023] [Indexed: 05/22/2023] Open
Abstract
BACKGROUND Regulatory T cells (Tregs) play an important role in regulation of immune response and immunologic tolerance in cancer. Gastrointestinal cancer is still a leading cause of cancer-related death in the world. This study aimed to detect Tregs in patients with gastrointestinal cancer. METHODS In this study, 45 gastric cancer patients, 50 colorectal cancer patients and 50 healthy controls were enrolled. Flow cytometry was used to detect CD4+CD25hiCD127low Tregs, CD4+CD25hi, and CD4+ cells in peripheral blood. Cytokine interleukin-10 (IL-10) and transforming growth factor-β1 (TGF-β1) in peripheral blood and in the supernatant of Tregs cultures were measured by enzyme linked immunosorbent assay. RESULTS Compared with healthy controls, the levels of CD4+CD25hiCD127low Tregs and CD4+CD25hi cells increased significantly in patients with gastrointestinal cancer. Patients with gastrointestinal cancer also showed a significantly increased levels of IL-10 and TGF-β1 in both peripheral blood and CD4+CD25hiCD127low Tregs culture medium. CONCLUSION The present study firstly demonstrated that gastrointestinal patients have a compromised immune status where the CD4+CD25hiCD127low Tregs, as well as levels of IL-10 and TGF-β1 are elevated. The data offered new information for understanding the immunological features of gastrointestinal patients, as well as provided new insights into approaches to develop new immunotherapies for patients with gastrointestinal cancer.
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Affiliation(s)
- Junlan Qiu
- Department of Oncology, Suzhou Science and Technology Town Hospital, Suzhou, Jiangsu, 215153, China.
| | - Weiqiang Shi
- Department of Pathology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215006, China
| | - Jin Zhang
- Department of Pathology, Suzhou Science and Technology Town Hospital, Suzhou, Jiangsu, 215153, China
| | - Qinqin Gao
- Institute for Fetology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215006, China
| | - Lin Feng
- Department of Oncology, Suzhou Science and Technology Town Hospital, Suzhou, Jiangsu, 215153, China
| | - Zhixiang Zhuang
- Department of Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215004, China
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Li Y, Choi H, Leung K, Jiang F, Graham DY, Leung WK. Global prevalence of Helicobacter pylori infection between 1980 and 2022: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol 2023; 8:553-564. [PMID: 37086739 DOI: 10.1016/s2468-1253(23)00070-5] [Citation(s) in RCA: 182] [Impact Index Per Article: 91.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2023] [Revised: 03/06/2023] [Accepted: 03/10/2023] [Indexed: 04/24/2023]
Abstract
BACKGROUND Few studies have examined the temporal trends of Helicobacter pylori prevalence worldwide. We aimed to identify the changes in global prevalence of H pylori infection between 1980 and 2022. METHODS In this systematic review and meta-analysis, we searched PubMed, Embase, MEDLINE, Scopus, and Web of Science, with no language restrictions, for observational studies on the prevalence of H pylori infection published between Jan 1, 1980, and Dec 31, 2022. Conference papers, meta-analyses, reviews, and case reports were excluded. We divided the study timeframe into four periods: 1980-90, 1991-2000, 2001-10, and 2011-22. Summary data were extracted from each selected publication. The prevalence of H pylori and its temporal trend were analysed according to WHO region, World Bank income level, WHO universal health coverage service coverage index of the country or region, sex and age of the patient, study type, and diagnostic method. The pooled prevalence was estimated by a random-effect meta-analysis, and the significance of the associated factors was analysed by multivariable meta-regression. This study is registered with the International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY), 2022100026. FINDINGS Of the 56 967 records identified, 5236 were included in the quality assessment stage and 224 studies-from 71 countries or regions from all six WHO regions and including 2 979 179 individuals-were included in the final analysis. Significant heterogeneity was found between studies (I2=99·9%). The estimated global prevalence of H pylori infection decreased from 58·2% (95% CI 50·7-65·8) in the 1980-90 period to 43·1% (40·3-45·9) in the 2011-22 period. Prevalence was relatively static between 1991 and 2010 but declined sharply between 2011 and 2022, with the largest decline in the WHO African region. Overall, a lower prevalence of H pylori infection was reported in younger people, high-income countries, or countries with high levels of universal health coverage, and by retrospective studies. Studies based on serological diagnostic methods generally reported higher H pylori prevalence than studies based on non-serological methods (53·2% [49·8-56·6] vs 41·1% [38·1-44·2]) and fluctuated less over time. INTERPRETATION This meta-analysis shows a declining trend of H pylori prevalence globally, particularly in the 2011-22 period. These results could help to inform future health policy on prevention and management of this important infection. However, a considerable degree of heterogeneity exists between studies and further population-based epidemiological studies are needed. FUNDING None.
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Affiliation(s)
- Yunhao Li
- Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China
| | - Horace Choi
- WHO Collaborating Centre for Infectious Disease Epidemiology and Control, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China; Laboratory of Data Discovery for Health, Hong Kong Special Administrative Region, China
| | - Kathy Leung
- WHO Collaborating Centre for Infectious Disease Epidemiology and Control, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China; Laboratory of Data Discovery for Health, Hong Kong Special Administrative Region, China; Department of Research, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
| | - Fang Jiang
- Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China
| | - David Y Graham
- Department of Medicine, Michael DeBakey VA Medical Center, Baylor College of Medicine, Houston, TX, USA
| | - Wai K Leung
- Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China.
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Combined Evaluation of mRNA and Protein Expression, Promoter Methylation, and Immune Infiltration of UBE2I in Pan-Digestive System Tumors. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2022; 2022:1129062. [PMID: 36193060 PMCID: PMC9526617 DOI: 10.1155/2022/1129062] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/09/2022] [Revised: 08/01/2022] [Accepted: 08/09/2022] [Indexed: 12/24/2022]
Abstract
Background Digestive system tumors (DSTs) have high morbidity and mortality worldwide. This study explored the potential value of ubiquitin-conjugating enzyme E2 I (UBE2I) in pan-digestive system tumors (pan-DSTs). Methods Differential expression, tumor stages, and survival outcomes of UBE2I in pan-DSTs were determined using the GEPIA database. The TIMER database was used to confirm the correlation of UBE2I expression with pan-DSTs and immune infiltrates. Differential analyses of UBE2I promoter methylation and protein levels were performed using the UALCAN database. The underlying mechanisms of UBE2I involvement in pan-DSTs were visualized using interaction networks. The diagnostic value of UBE2I in pan-DSTs was identified using the Oncomine database. Results UBE2I was differentially and highly expressed in cholangiocarcinoma (CHOL), pancreatic adenocarcinoma (PAAD), colon adenocarcinoma (COAD), rectal adenocarcinoma (READ), liver hepatocellular carcinoma (LIHC), and stomach adenocarcinoma (STAD). According to survival analysis, upregulated UBE2I was associated with adverse overall and disease-free survival in PAAD and favorable overall survival in READ. UBE2I expression was partially linked to the purity of immune infiltration in COAD, LIHC, PAAD, READ, and STAD, as indicated by the immune infiltration analysis. Promoter methylation analysis showed differential and high methylation of UBE2I in PAAD as well as stratified analysis by gender, nodal metastasis, and race. Protein expression analysis in colon cancer revealed that UBE2I had differential and high expression in tumors as well as stratified analysis by gender, tumor histology, race, and tumor stage. Mechanism explorations demonstrated that in COAD and PAAD, UBE2I was involved in spliceosomal snRNP complex, Notch signaling pathway, etc. Diagnostic analysis indicated that UBE2I had consistent diagnostic value for COAD and PAAD. Conclusions Upregulated UBE2I may be a diagnostic and surveillance predictive signature for PAAD and COAD. The potential significance of immune infiltrates and promoter methylation in PAAD and COAD needs further exploration.
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Bioinformatics Analysis Based on TCGA: MUC16 Mutation Correlates with Clinical Outcome in Gastric Cancer. DISEASE MARKERS 2022; 2022:6734105. [PMID: 36051359 PMCID: PMC9427262 DOI: 10.1155/2022/6734105] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/26/2022] [Revised: 07/25/2022] [Accepted: 07/27/2022] [Indexed: 11/18/2022]
Abstract
The prognosis of gastric cancer (GC) is difficult to predict due to the disease's complex genetic and phenotypic characteristics. MUC16 has been reported to be involved in the progression of several tumors. In this study, we aimed to explore whether MUC16 mutation had any impact on the prognosis or treatments of GC patients. Additionally, this analysis uncovered possible critical pathways related with these systems. On the cBioPortal, we were able to locate the pertinent data of patients with MUC16 mutations. And then, GSEA analysis identified differences in mRNA levels between mutant and wild-type MUC16 patients in terms of biological function annotation and pathways. The KEGG and GO analyses were also performed using the differentially expressed genes (DEGs). There were 139 individuals with GC who had the MUC16 mutation, which accounts for 32 percent, and the remaining patients had the MUC16 wild type. Survival assays revealed that patients with the MUC16 mutation had longer overall survival and disease-free survival. GSEA analysis revealed that cell cycle, cysteine and methionine metabolism, Huntington's disease, one carbon pool by folate, pyrimidine metabolism, pyruvate metabolism, RNA degradation, spliceosome, and valine leucine and isoleucine degradation were distinctly enriched in patients with MUC16 mutation type. Moreover, we identified 323 DEGs. Among them, 162 genes were upregulated, and 161 genes were downregulated. GO and KEGG assays indicated DEGs as enriched in pancreatic secretion, neuroactive ligand-receptor interaction, protein digestion and absorption, fat digestion and absorption, and glycerolipid metabolism. Overall, our data revealed that the MUC16 mutation in GC may affect the development of patients by altering several genes and pathways, indicating the importance of MUC16 mutation in the treatments of GC on an individual basis.
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Proteomic Analysis Reveals Molecular Differences in the Development of Gastric Cancer. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2022; 2022:8266544. [PMID: 35958927 PMCID: PMC9357686 DOI: 10.1155/2022/8266544] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Revised: 06/18/2022] [Accepted: 06/23/2022] [Indexed: 02/08/2023]
Abstract
Gastric cancer (GC) is the 3rd leading cause of death from cancer and the 5th most common cancer worldwide. The detection rate of GC among Tibetans is significantly higher than that in Han Chinese, probably due to differences in their living habits, dietary structure, and environment. Despite such a high disease burden, the epidemiology of gastric cancer has not been studied in this population. Molecular markers are required to aid the diagnosis and treatment of GC. In this study, we collected gastric tissue samples from patients in Tibet with chronic nonatrophic gastritis (CNAG) (n = 6), chronic atrophic gastritis (CAG) (n = 7), gastric intraepithelial neoplasia (GIN) (n = 4), and GC (n = 5). The proteins in each group were analyzed using coupled label-free mass spectrometry. In addition, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, and protein interaction networks were used to analyze the differentially expressed proteins (DEPs) among groups. DEPs were quantified in comparisons of GC versus CNAG (223), GC versus GIN (100), and GIN versus CNAG (341). GO and KEGG analyses showed that the DEPs were mainly associated with immunity (GC versus CNAG) and cancer proliferation and metastasis (GC versus GIN, and GIN versus CNAG). Furthermore, the expression levels of cell proliferation and cytoskeleton-related proteins increased consistently during cancer development, such as ITGA4, DDC, and CPT1A; thus, they are potential diagnostic markers. These results obtained by proteomics analysis could improve our understanding of cancer biology in GC and provide a rich resource for data mining and discovering potential immunotherapy targets.
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Tang Y, Dong L, Zhang C, Li X, Li R, Lin H, Qi Y, Tang M, Peng Y, Liu C, Zhou J, Hou N, Liu W, Yang G, Yang X, Teng Y. PRMT5 acts as a tumor suppressor by inhibiting Wnt/β-catenin signaling in murine gastric tumorigenesis. Int J Biol Sci 2022; 18:4329-4340. [PMID: 35864961 PMCID: PMC9295066 DOI: 10.7150/ijbs.71581] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2022] [Accepted: 05/21/2022] [Indexed: 11/05/2022] Open
Abstract
Previous studies have demonstrated the in vitro oncogenic role of protein arginine methyltransferase 5 (PRMT5) in gastric cancer cell lines. The in vivo function of PRMT5 in gastric tumorigenesis, however, is still unexplored. Here, we showed that Prmt5 deletion in mouse gastric epithelium resulted in spontaneous tumorigenesis in gastric antrum. All Prmt5-deficient mice displayed intestinal-type gastric cancer within 4 months of age. Of note, 20% (2/10) of Prmt5 mutants finally developed into invasive gastric cancer by 8 months of age. Gastric cancer caused by PRMT5 loss exhibited the increase in Lgr5+ stem cells, which are proposed to contribute to both the gastric tumorigenesis and progression in mouse models. Consistent with the notion that Lgr5 is the target of Wnt/β-catenin signaling, whose activation is the most predominant driver for gastric tumorigenesis, Prmt5 mutant gastric cancer showed the activation of Wnt/β-Catenin signaling. Furthermore, in human gastric cancer samples, PRMT5 deletion and downregulation were frequently observed and associated with the poor prognosis. We propose that as opposed to the tumor-promoting role of PRMT5 well-established in the progression of various cancer types, PRMT5 functions as a tumor suppressor in vivo, at least during gastric tumor formation.
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Affiliation(s)
- Yuling Tang
- State Key Laboratory of Proteomics, Beijing Proteome Research Centre, National Centre for Protein Sciences, Beijing Institute of Lifeomics, Beijing 102206, China.,Laboratory Animal Center, the Academy of Military Medical Sciences, Beijing 100071, China
| | - Lei Dong
- State Key Laboratory of Proteomics, Beijing Proteome Research Centre, National Centre for Protein Sciences, Beijing Institute of Lifeomics, Beijing 102206, China
| | - Chong Zhang
- State Key Laboratory of Proteomics, Beijing Proteome Research Centre, National Centre for Protein Sciences, Beijing Institute of Lifeomics, Beijing 102206, China
| | - Xiubin Li
- Department of Urology, the Third Medical Center of Chinese PLA General Hospital, Beijing 100039, China
| | - Rongyu Li
- State Key Laboratory of Proteomics, Beijing Proteome Research Centre, National Centre for Protein Sciences, Beijing Institute of Lifeomics, Beijing 102206, China
| | - Huisang Lin
- State Key Laboratory of Proteomics, Beijing Proteome Research Centre, National Centre for Protein Sciences, Beijing Institute of Lifeomics, Beijing 102206, China
| | - Yini Qi
- State Key Laboratory of Proteomics, Beijing Proteome Research Centre, National Centre for Protein Sciences, Beijing Institute of Lifeomics, Beijing 102206, China
| | - Mingchuan Tang
- State Key Laboratory of Proteomics, Beijing Proteome Research Centre, National Centre for Protein Sciences, Beijing Institute of Lifeomics, Beijing 102206, China
| | - Yanli Peng
- State Key Laboratory of Proteomics, Beijing Proteome Research Centre, National Centre for Protein Sciences, Beijing Institute of Lifeomics, Beijing 102206, China
| | - Chuan Liu
- State Key Laboratory of Proteomics, Beijing Proteome Research Centre, National Centre for Protein Sciences, Beijing Institute of Lifeomics, Beijing 102206, China
| | - Jian Zhou
- State Key Laboratory of Proteomics, Beijing Proteome Research Centre, National Centre for Protein Sciences, Beijing Institute of Lifeomics, Beijing 102206, China
| | - Ning Hou
- State Key Laboratory of Proteomics, Beijing Proteome Research Centre, National Centre for Protein Sciences, Beijing Institute of Lifeomics, Beijing 102206, China
| | - Wenjia Liu
- State Key Laboratory of Proteomics, Beijing Proteome Research Centre, National Centre for Protein Sciences, Beijing Institute of Lifeomics, Beijing 102206, China
| | - Guan Yang
- State Key Laboratory of Proteomics, Beijing Proteome Research Centre, National Centre for Protein Sciences, Beijing Institute of Lifeomics, Beijing 102206, China
| | - Xiao Yang
- State Key Laboratory of Proteomics, Beijing Proteome Research Centre, National Centre for Protein Sciences, Beijing Institute of Lifeomics, Beijing 102206, China
| | - Yan Teng
- State Key Laboratory of Proteomics, Beijing Proteome Research Centre, National Centre for Protein Sciences, Beijing Institute of Lifeomics, Beijing 102206, China
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Ma J, Meng Y, Zhou X, Guo L, Fu W. The Prognostic Significance and Gene Expression Characteristics of Gastric Signet-Ring Cell Carcinoma: A Study Based on the SEER and TCGA Databases. Front Surg 2022; 9:819018. [PMID: 35372476 PMCID: PMC8967986 DOI: 10.3389/fsurg.2022.819018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2021] [Accepted: 02/07/2022] [Indexed: 11/13/2022] Open
Abstract
PurposeThis study is based on the Surveillance, Epidemiology, and End Results (SEER) program to explore the prognostic differences between signet-ring cell carcinoma (SRC) and intestinal-type gastric carcinoma (ITGC). This study is also based on gene sequencing data from The Cancer Genome Atlas (TCGA) to identify unique genetic contributions to the prognostic differences between the two subtypes of gastric cancer.Patients and MethodsThe clinical data were based on the SEER database from 2004 to 2015. Kaplan–Meier (KM) curves were used to compare 5-year overall survival (OS), and Cox regression was used for univariate and multivariate analyses. Gene expression profiles were obtained from TCGA database, and differentially expressed genes (DEGs) were screened. Functional enrichment analysis, protein interaction and survival analysis will be further carried out. Genes of interest were verified by the Human Protein Atlas, immunohistochemistry, and encyclopedia of Cancer Cell Lines (CCLE). The relationship between genes of interest and immune cell infiltration was also analyzed by Tumor Immune Estimation Resource (TIMER).ResultsCompared with ITGC patients, SRC patients were more likely to be female, tended to be younger, and have a greater tumor distribution in the middle and lower stomach (p < 0.01). SRCs showed a significantly better prognosis than ITGCs (p < 0.01) in early gastric cancer (EGC), while the prognosis of SRCs was significantly worse than ITGCs (p < 0.05) in advanced gastric cancer (AGC). A total of 256 DEGs were screened in SRCs compared to ITGCs, and the enrichment analysis and protein interactions revealed that differential genes were mainly related to extracellular matrix organization. Thrombospondin1 (THBS1) and serpin peptidase inhibitor, clade E, member 1 (SERPINE1) are significantly differentially expressed between SRC and ITGC, which has been preliminarily verified by immunohistochemistry and open-source databases. THBS1 and SERPINE1 are also associated with multiple immune cell infiltrates in gastric cancer.ConclusionsThere were significant differences in the clinicopathological features and prognosis between SRC and ITGC. These results suggest that SRC and ITGC may be two distinct types of tumors with different pathogeneses. We found many codifferentially expressed genes and important pathways between SRC and ITGC. THBS1 and SERPINE1 were significantly differentially expressed in the two types of gastric cancer, and may have potentially important functions.
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Affiliation(s)
- Junren Ma
- Department of General Surgery, Peking University Third Hospital, Beijing, China
| | - Yan Meng
- Department of General Surgery, Peking University Third Hospital, Beijing, China
| | - Xin Zhou
- Department of General Surgery, Peking University Third Hospital, Beijing, China
- Peking University Third Hospital Cancer Center, Beijing, China
- *Correspondence: Xin Zhou
| | - Limei Guo
- Department of Pathology, Peking University Third Hospital, Beijing, China
- Limei Guo
| | - Wei Fu
- Department of General Surgery, Peking University Third Hospital, Beijing, China
- Peking University Third Hospital Cancer Center, Beijing, China
- Wei Fu
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Hsieh HL, Yu MC, Cheng LC, Yeh TS, Tsai MM. Molecular mechanism of therapeutic approaches for human gastric cancer stem cells. World J Stem Cells 2022; 14:76-91. [PMID: 35126829 PMCID: PMC8788185 DOI: 10.4252/wjsc.v14.i1.76] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2021] [Revised: 05/15/2021] [Accepted: 12/21/2021] [Indexed: 02/06/2023] Open
Abstract
Gastric cancer (GC) is a primary cause of cancer-related mortality worldwide, and even after therapeutic gastrectomy, survival rates remain poor. The presence of gastric cancer stem cells (GCSCs) is thought to be the major reason for resistance to anticancer treatment (chemotherapy or radiotherapy), and for the development of tumor recurrence, epithelial-mesenchymal transition, and metastases. Additionally, GCSCs have the capacity for self-renewal, differentiation, and tumor initiation. They also synthesize antiapoptotic factors, demonstrate higher performance of drug efflux pumps, and display cell plasticity abilities. Moreover, the tumor microenvironment (TME; tumor niche) that surrounds GCSCs contains secreted growth factors and supports angiogenesis and is thus responsible for the maintenance of the growing tumor. However, the genesis of GCSCs is unclear and exploration of the source of GCSCs is essential. In this review, we provide up-to-date information about GCSC-surface/intracellular markers and GCSC-mediated pathways and their role in tumor development. This information will support improved diagnosis, novel therapeutic approaches, and better prognosis using GCSC-targeting agents as a potentially effective treatment choice following surgical resection or in combination with chemotherapy and radiotherapy. To date, most anti-GCSC blockers when used alone have been reported as unsatisfactory anticancer agents. However, when used in combination with adjuvant therapy, treatment can improve. By providing insights into the molecular mechanisms of GCSCs associated with tumors in GC, the aim is to optimize anti-GCSCs molecular approaches for GC therapy in combination with chemotherapy, radiotherapy, or other adjuvant treatment.
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Affiliation(s)
- Hsi-Lung Hsieh
- Department of Nursing, Division of Basic Medical Sciences, Chang-Gung University of Science and Technology, Taoyuan 333, Taiwan
- Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan 333, Taiwan
- Department of Neurology, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan
| | - Ming-Chin Yu
- Department of General Surgery, Chang Gung Memorial Hospital at Linkou, Taoyuan 333, Taiwan
- College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
- Department of General Surgery, New Taipei Municipal TuCheng Hospital, New Taipei 236, Taiwan
| | - Li-Ching Cheng
- Department of Nursing, Division of Basic Medical Sciences, Chang-Gung University of Science and Technology, Taoyuan 333, Taiwan
| | - Ta-Sen Yeh
- Department of General Surgery, Chang Gung Memorial Hospital at Linkou, Taoyuan 333, Taiwan
- College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
| | - Ming-Ming Tsai
- Department of Nursing, Division of Basic Medical Sciences, Chang-Gung University of Science and Technology, Taoyuan 333, Taiwan
- Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan 333, Taiwan
- Department of General Surgery, Chang Gung Memorial Hospital, Chiayi 613, Taiwan.
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Chen Q, Lin L, Xiong B, Yang W, Huang J, Shi H, Wang Z. MiR-873-5p targets THUMPD1 to inhibit gastric cancer cell behavior and chemoresistance. J Gastrointest Oncol 2021; 12:2061-2072. [PMID: 34790374 DOI: 10.21037/jgo-21-641] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2021] [Accepted: 10/22/2021] [Indexed: 12/12/2022] Open
Abstract
Background Gastric cancer is one of the most common gastrointestinal tumors. Evidence has pointed to the fact that miRNAs play critical roles in the occurrence, development, and metastasis of gastric cancer by regulating cell proliferation, differentiation, apoptosis, and invasion. Methods In this study, first the relationship of miR-873-5p level and tissues types/LN(+/-)/metastasis(+/-)/tumor size was analysis, respectively. Second, the CCK8 and Transwell assay was used to determine the proliferation, invasion and migration of GC cells transfected with overexpression-/low expression-miR-873-5p. Third, the cell viability were analysis in the GC cells transfected with overexpression-/low expression-miR-873-5p treatment with different chemotherapy drugs. Fourth, the target gene of miR-873-5p was predicted using bioinformation methods. Fifth, the relationship of miR-873-5p with target gene-THUMPD1 were explored by using Wb and luciferase activity assay, et al. Results We confirmed that miR-873-5p was negatively correlated with GC including tumor size, LN metastasis, distant metastasis. The miR-873-5p enhanced the sensitivity of Doxorubicin/Fluorouracil and cisplatin. The THUMPD1 was the target gene of miR-873-5p. Moreover, miR-873-5p could target the THUMPD1 axis so as to inhibit gastric cancer cell behavior as well as chemoresistance. Conclusions MiR-873-5p plays a role in regulating cell behavior as well as regulating chemoresistance in gastric cancer. In addition, THUMPD1, as a downstream molecule of miR-873-5p, plays an important role in the cell behavior and chemoresistance of gastric cancer. The research first confirmed that miR-873-5p could inhibit gastric cancer cell behavior and chemoresistance by targeting the THUMPD1.
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Affiliation(s)
- Qinggui Chen
- Department of General Surgery, Zhongshan Hospital, Xiamen University, Xiamen, China
| | - Li Lin
- Department of Gastrointestinal Surgery, Zhongshan Hospital, Xiamen University, Xiamen, China
| | - Boliang Xiong
- Department of Radiotherapy, Zhongshan Hospital, Xiamen University, Xiamen, China
| | - Wensheng Yang
- Department of Pathology, Chenggong Hospital, Xiamen University, Xiamen, China
| | - Junli Huang
- Department of General Surgery, Chenggong Hospital, Xiamen University, Xiamen, China
| | - Huibo Shi
- Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.,Key Laboratory of Organ Transplantation, Ministry of Education NHC Key Laboratory of Organ Transplantation, Wuhan, China
| | - Zhenfa Wang
- Department of Gastrointestinal Surgery, Zhongshan Hospital, Xiamen University, Xiamen, China
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20
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Zheng L, Wu Y, Shen L, Liang X, Yang Z, Li S, Li T, Shang W, Shao W, Wang Y, Liu F, Ma L, Jia J. Mechanisms of JARID1B Up-Regulation and Its Role in Helicobacter pylori-Induced Gastric Carcinogenesis. Front Oncol 2021; 11:757497. [PMID: 34778074 PMCID: PMC8581301 DOI: 10.3389/fonc.2021.757497] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2021] [Accepted: 10/07/2021] [Indexed: 11/13/2022] Open
Abstract
Gastric cancer (GC) is the third leading cause of cancer-related death worldwide. Helicobacter pylori infection can induce GC through a serial cascade of events, with emerging evidence suggesting the important role of epigenetic alterations in the development and progression of the disease. Here, we report on mechanisms responsible for Jumonji AT-rich interactive domain1B (JARID1B) upregulation in GC and its role in the malignant transformation induced by H. pylori infection. We found that upregulation of JARID1B was associated with poorer prognosis, greater tumor purity, and less immune cell infiltration into the tumor. Mechanistically, we showed that the upregulation of JARID1B in human GC was attributed to JARID1B amplification and its induction by H. pylori infection. Furthermore, we identified miR-29c as a negative regulator of JARID1B in GC. H. pylori caused downregulation of miR-29c in human GC and thereby contributed to JARID1B upregulation through relieving posttranscriptional regulation. Functionally, we showed that knockdown of JARID1B reduced GC cell proliferation induced by H. pylori infection. Subsequently, cyclinD1 (CCND1), a key molecule in GC, was shown to be a target gene of JARID1B. In conclusion, these results suggest that JARID1B may be an oncogene upregulated in human GC and could represent a novel therapeutic target to prevent malignant transformation induced by H. pylori infection.
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Affiliation(s)
- Lixin Zheng
- Key Laboratory of Experimental Teratology, School of Basic Medical Sciences, Shandong University, Jinan, China
| | - Yujiao Wu
- Key Laboratory of Experimental Teratology, School of Basic Medical Sciences, Shandong University, Jinan, China
| | - Li Shen
- Key Laboratory of Experimental Teratology, School of Basic Medical Sciences, Shandong University, Jinan, China
| | - Xiuming Liang
- Key Laboratory of Experimental Teratology, School of Basic Medical Sciences, Shandong University, Jinan, China
| | - Zongcheng Yang
- Key Laboratory of Experimental Teratology, School of Basic Medical Sciences, Shandong University, Jinan, China
| | - Shuyan Li
- Key Laboratory of Experimental Teratology, School of Basic Medical Sciences, Shandong University, Jinan, China
| | - Tongyu Li
- Key Laboratory of Experimental Teratology, School of Basic Medical Sciences, Shandong University, Jinan, China
| | - Wenjing Shang
- Key Laboratory of Experimental Teratology, School of Basic Medical Sciences, Shandong University, Jinan, China
| | - Wei Shao
- Key Laboratory of Experimental Teratology, School of Basic Medical Sciences, Shandong University, Jinan, China
| | - Yue Wang
- Key Laboratory of Experimental Teratology, School of Basic Medical Sciences, Shandong University, Jinan, China
| | - Fen Liu
- Key Laboratory of Experimental Teratology, School of Basic Medical Sciences, Shandong University, Jinan, China
| | - Lin Ma
- Key Laboratory of Experimental Teratology, School of Basic Medical Sciences, Shandong University, Jinan, China
| | - Jihui Jia
- Key Laboratory of Experimental Teratology, School of Basic Medical Sciences, Shandong University, Jinan, China.,Shandong Provincial Key Laboratory of Infection and Immunology, School of Basic Medical Sciences, Shandong University, Jinan, China
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21
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Huang H, Xie L, Feng X, Zheng Z, Ouyang J, Li Y, Yu J. An integrated analysis of DNA promoter methylation, microRNA regulation, and gene expression in gastric adenocarcinoma. ANNALS OF TRANSLATIONAL MEDICINE 2021; 9:1414. [PMID: 34733966 PMCID: PMC8506766 DOI: 10.21037/atm-21-3211] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/02/2021] [Accepted: 08/04/2021] [Indexed: 12/24/2022]
Abstract
Background Gastric adenocarcinoma (GAC), a common type of gastric cancer, poses a significant public health threat worldwide. This study aimed to determine the transcriptional regulatory mechanisms of GAC. Methods HTSeq-FPKM raw data were obtained from The Cancer Genome Atlas Stomach Adenocarcinoma data collection. Subsequently, the limma package in R was used to identify differentially expressed genes (DEGs). Differentially methylated genes (DMGs), DEGs, and differentially expressed microRNAs (miRNAs) in normal, and tumor tissues of the same patients were screened and compared using R software tools. A functional enrichment analysis was performed using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) for various DEGs, DMGs, promoter methylation, and miRNAs. DEG-specific methylation and transcription factors were analyzed using ENCODE ChIP-seq. Results DEGs were centrally modified by the histone trimethylation of lysine 27 on histone H3 (H3K27me3). Upstream transcription factors of DEGs were enriched in different ChIP-seq clusters, such as Forkhead Box M1, E2F Transcription Factor 4, and suppressor of zest 12. Integrated regulatory networks of DEGs, promoter methylation, and miRNAs were constructed. Two miRNAs (hsa-mir-1 and hsa-mir-133a) and four DEGs (A disintegrin and metalloproteinase domain 12, transcription factor AP-2 alpha, solute carrier family 5 member 7, and cadherin 19) separately played important roles in the integrated regulatory network. Therefore, these DEGs, DMGs, promoter methylation, and miRNAs may play an important role in GAC pathogenesis. Conclusions In summary, the present study results provide insights into the oncogenesis and progression of GAC, thus accelerating the development of novel targeted GAC therapies.
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Affiliation(s)
- Hongyun Huang
- Department of General Surgery of Zhujiang Hospital, Southern Medical University, Guangzhou, China.,The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China
| | - Lang Xie
- Department of General Surgery of Zhujiang Hospital, Southern Medical University, Guangzhou, China.,The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China
| | - Xiaoxuan Feng
- The First School of Clinical Medicine, Southern Medical University, Guangzhou, China
| | - Zheng Zheng
- Department of General Surgery of Zhujiang Hospital, Southern Medical University, Guangzhou, China
| | - Juntao Ouyang
- The First School of Clinical Medicine, Southern Medical University, Guangzhou, China
| | - Yan Li
- Department of Immunology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China
| | - Jinlong Yu
- Department of General Surgery of Zhujiang Hospital, Southern Medical University, Guangzhou, China.,The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China
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22
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Song Y, Chang L, Wang X, Tan B, Li J, Zhang J, Zhang F, Zhao L, Liu G, Huo B. Regulatory Mechanism and Experimental Verification of Patchouli Alcohol on Gastric Cancer Cell Based on Network Pharmacology. Front Oncol 2021; 11:711984. [PMID: 34540679 PMCID: PMC8440821 DOI: 10.3389/fonc.2021.711984] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2021] [Accepted: 08/12/2021] [Indexed: 12/12/2022] Open
Abstract
Background Pogostemon cablin is a traditional Chinese medicine (TCM) that is frequently used to treat various gastrointestinal diseases. Patchouli alcohol (PA), a compound extracted from the Pogostemon cablin, has been shown to have anti-tumor efficacy in human colorectal cancer. However, the mechanism of PA’s anticancer effect on gastric cancer (GC) remains unknown. Methods We used the public database to obtain the potential targets of PA and genes related to GC. Bioinformatic analyses, such as the Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), and protein-protein interactions (PPI), were used for analyzing the potential signal pathways and targets. Cell experiments were also conducted to further explain the impact and molecular mechanism of PA on GC, as well as to confirm the findings of network pharmacology. Results Using network pharmacological analysis, 161 possible targets were identified for the treatment of GC. Network analysis and functional enrichment analysis show that PA produced a marked effect in the treatment of GC through multi-targets and multi-pathways, especially the MAPK and PI3K/AKT signal pathways. In addition, PA showed the inhibition of GC cell proliferation, migration and invasion in cell experiments. According to our findings, PA could also cause G0/G1 phase arrest and apoptosis in GC cells. Conclusion Using network pharmacology, we aim to uncover the possible molecular mechanism of PA on GC treatment in this research. Cell experiments were also conducted to confirm the therapeutic effect of PA on GC.
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Affiliation(s)
- Yanru Song
- Department of Traditional Chinese Medicine, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Liang Chang
- Department of Basic Theory of Traditional Chinese Medicine of Basic Medical Science College, HeBei University of Chinese Medicine, Shijiazhuang, China
| | - Xiaoyuan Wang
- Department of Traditional Chinese Medicine, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Bibo Tan
- Department of General Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Jianbo Li
- Department of Traditional Chinese Medicine, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Jie Zhang
- Department of Traditional Chinese Medicine, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Fengbin Zhang
- Department of Gastroenterology Pharmacology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Lianmei Zhao
- Research Centre, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Guangjie Liu
- Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Bingjie Huo
- Department of Traditional Chinese Medicine, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
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23
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Xu W, Zhou B, Wang J, Tang L, Hu Q, Wang J, Chen H, Zheng J, Yan F, Chen H. tRNA-Derived Fragment tRF-Glu-TTC-027 Regulates the Progression of Gastric Carcinoma via MAPK Signaling Pathway. Front Oncol 2021; 11:733763. [PMID: 34497772 PMCID: PMC8419445 DOI: 10.3389/fonc.2021.733763] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Accepted: 08/05/2021] [Indexed: 01/25/2023] Open
Abstract
Transfer RNA-derived RNA fragments (tRFs) belong to non-coding RNAs (ncRNAs) discovered in most carcinomas. Although some articles have demonstrated the characteristics of tRFs in gastric carcinoma (GC), the underlying mechanisms still need to be elucidated. Meanwhile, it was reported that the MAPK pathway was momentous in GC progression. Thus we focused on investigating whether tRF-Glu-TTC-027 could act as a key role in the progression of GC with the regulation of the MAPK pathway. We collected the data of the tRNA-derived fragments expression profile from six paired clinical GC tissues and corresponding adjacent normal samples in this study. Then we screened tRF-Glu-TTC-027 for analysis by using RT-PCR. We transfected GC cell lines with tRF-Glu-TTC-027 mimics or mimics control. Then the proliferation, migration, and invasion assays were performed to assess the influence of tRF-Glu-TTC-027 on GC cell lines. Fluorescence in situ hybridization assay was conducted to confirm the cell distribution of tRF-Glu-TTC-027. We confirmed the mechanism that tRF-Glu-TTC-027 influenced the MAPK signaling pathway and observed a strong downregulation of tRF-Glu-TTC-027 in clinical GC samples. Overexpression of tRF-Glu-TTC-027 suppressed the malignant activities of GC in vitro and in vivo. MAPK signaling pathway was confirmed to be a target pathway of tRF-Glu-TTC-027 in GC by western blot. This is the first study to show that tRF-Glu-TTC-027 was a new tumor-suppressor and could be a potential object for molecular targeted therapy in GC.
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Affiliation(s)
- Weiguo Xu
- Department of General Surgery, Jiangsu Cancer Hospital & The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Institute of Cancer Research, Nanjing, China
| | - Bin Zhou
- Department of General Surgery, Jiangsu Cancer Hospital & The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Institute of Cancer Research, Nanjing, China
| | - Juan Wang
- Department of Oncology, Jiangsu Cancer Hospital & The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Institute of Cancer Research, Nanjing, China
| | - Li Tang
- Department of Clinical Laboratory, Jiangsu Cancer Hospital & The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Institute of Cancer Research, Nanjing, China
| | - Qing Hu
- Department of General Surgery, Jiangsu Cancer Hospital & The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Institute of Cancer Research, Nanjing, China
| | - Jian Wang
- Department of General Surgery, Jiangsu Cancer Hospital & The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Institute of Cancer Research, Nanjing, China
| | - Huanhuan Chen
- Department of Clinical Laboratory, Jiangsu Cancer Hospital & The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Institute of Cancer Research, Nanjing, China
| | - Junyu Zheng
- Department of Clinical Laboratory, Jiangsu Cancer Hospital & The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Institute of Cancer Research, Nanjing, China
| | - Feng Yan
- Department of Clinical Laboratory, Jiangsu Cancer Hospital & The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Institute of Cancer Research, Nanjing, China
| | - Huanqiu Chen
- Department of General Surgery, Jiangsu Cancer Hospital & The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Institute of Cancer Research, Nanjing, China
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Zhou C, Chen L, Chen R, Xu F, Huang Z, Huang R, Wang W, Xu Q. miR-4486 enhances cisplatin sensitivity of gastric cancer cells by restraining the JAK3/STAT3 signalling pathway. J Chemother 2021; 34:35-44. [PMID: 34167436 DOI: 10.1080/1120009x.2021.1936957] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Along with the occurrence of cisplatin resistance, treatment on gastric cancer (GC) becomes difficult. Therefore, researches on new therapeutic methods to revert cisplatin resistance are becoming increasingly urgent. qRT-PCR was used to quantify the expression of miR-4486, JAK3 in SGC-7901 or SGC-7901/DDP cell lines. WB was utilized to analyze the expression of JAK3, STAT3 and p-STAT3 in SGC-7901/DDP cell lines. CCK-8 assay was used to determine the IC50 of cisplatin on both cell lines and cell viability of SGC-7901/DDP cell lines. The target relationship between miR-4486 and JAK3 was determined by luciferase assay. MiR-4486 expression on apoptosis of SGC-7901/DDP cell lines was determined by flow cytometry. qRT-PCR testified that miR-4486 decreased in SGC-7901/DDP cells, and the expression of miR-4486 mimic increased significantly compared with miR-4486 NC. By CCK-8 assay, the IC50 of cisplatin on both cell lines were 9 μg/mL and 81.3 μg/mL, and overexpression of miR-4486 decreased the viability of SGC-7901/DDP cells. Compared with DDP group, the expression of miR-4486 accelerated SGC-7901/DDP cells apoptosis. Dual-luciferase assay suggested that JAK3 was the target gene of miR-4486. qRT-PCR and WB proved that miR-4486/JAK3 axis inhibit the activation of JAK3/STAT3 pathway, and JAK3 overexpression can partly reverse this. As shown by CCK-8 and flow cytometry, miR-4486 overexpression decreased viability and stimulated apoptosis of SGC-7901/DDP cells. However, JAK3 overexpression can also partly revert this. miR-4486 overexpression could decrease viability and improve apoptosis of SGC-7901/DDP cells to revert its cisplatin-resistance, and the mechanism may be related to JAK3/STAT3 signalling pathway.
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Affiliation(s)
- Caijin Zhou
- Department of Gastrointestinal Surgery, the Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China
| | - Linxia Chen
- Department of Operating Room, the Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China
| | - Rihong Chen
- Department of Gastrointestinal Surgery, the Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China
| | - Feipeng Xu
- Department of Gastrointestinal Surgery, the Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China
| | - Zhe Huang
- Department of Gastrointestinal Surgery, the Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China
| | - Renwei Huang
- Department of Gastrointestinal Surgery, the Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China
| | - Weiwei Wang
- Department of Gastrointestinal Surgery, the Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China
| | - Qingwen Xu
- Department of Gastrointestinal Surgery, the Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China
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25
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Effects of Berberine on Circular RNA Expression Profiles in Human Gastric Cancer Cells. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2021; 2021:6688629. [PMID: 34055022 PMCID: PMC8112944 DOI: 10.1155/2021/6688629] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/02/2021] [Revised: 03/23/2021] [Accepted: 03/29/2021] [Indexed: 12/24/2022]
Abstract
Background Berberine has been demonstrated to have anticancer effects against gastric cancer (GC), but the mechanism of these actions is unclear. Objectives To explore the impact of berberine on circular RNA (circRNA) expression profiles in GC and investigate the potential molecular mechanisms associated with circRNAs in GC. Methods AGS and HGC27 GC cells were treated with various concentrations of berberine. Cell viability was measured using a Cell Counting Kit-8 assay. Cell proliferation was measured using a cell colony formation assay. Cell apoptosis was measured using flow cytometry. The mitochondrial membrane potential (Δψm) was determined using a JC-1 probe. RNA-seq was performed to identify circRNA expression profiles in AGS cells after berberine treatment. Selected differentially expressed (DE) circRNAs were verified using RT-qPCR. Bioinformatics analysis was performed to predict target miRNAs and mRNAs and construct a circRNA-miRNA-mRNA network. Pathway and process enrichment analyses were performed to explore the potential biological roles of DE circRNAs. Results Berberine decreased GC cell viability, cell proliferation, and Δψm and induced cell apoptosis. Thirty-one DE circRNAs were identified in the berberine-treated group compared to the control group, among which circRNA2499, hsa_circ_0003423, and hsa_circ_0006702 were validated using RT-qPCR. Enrichment analyses, based on the host genes of these 31 DE circRNAs and putative target mRNAs in the circRNA-miRNA-mRNA network of the validated circRNAs, indicated that berberine exerts anti-GC effects in multiple pathways including the Notch, MAPK, and NF-κB signaling pathways via specific circRNAs. Conclusion This study elucidated the expression profile of circRNAs in human GC cells after berberine treatment. Our results demonstrate that berberine has the potential to influence cancer-related pathways by regulating circRNA expression and their corresponding target genes in GC cells.
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Xiao J, Zhu C, Ni P, Chen W, Li Z, Fan H, Ma X, Xu Z, Yang L. Correlations of SNHG5 genetic polymorphisms with susceptibility and prognosis to gastric cancer in a Chinese population. Genomics 2021; 113:1754-1760. [PMID: 33865958 DOI: 10.1016/j.ygeno.2021.04.025] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2020] [Revised: 03/16/2021] [Accepted: 04/12/2021] [Indexed: 12/29/2022]
Abstract
The most studied genetic polymorphisms associated with gastric cancer (GC) risk are located in protein-coding genes. However, these sited in long noncoding RNA (lncRNA) are not adequately explored yet. Here, we designed a case-control study of 848 cases and 880 controls to investigate the associations of polymorphisms (rs61396151, rs1059307, rs11961028, rs9351065) in lncRNA SNHG5 with the risk and prognosis of GC. The results indicate rs61396151 associated with decreased risk of GC (OR = 0.78, 95% CI = 0.62-0.96), but there were no correlations observed with the clinicopathological features of GC (P > 0.05). However, the CA genotype of rs61396151 was correlated with poor overall survival rate in a multivariate cox regression model (HR = 1.91, P = 0.040), but it was reversed with adjustment for age, gender and TNM stage (HR = 1.35, P = 0.213). Collectively, our results highlight the importance of SNHG5-related polymorphisms to GC susceptibility and prognosis.
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Affiliation(s)
- Jian Xiao
- Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Chuming Zhu
- Department of General Surgery, Liyang People's Hospital, Liyang Branch Hospital of Jiangsu Province Hospital, Liyang, Jiangsu Province, China
| | - Peidong Ni
- Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Wangwang Chen
- Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Zengliang Li
- Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Hao Fan
- Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Xiang Ma
- Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Zekuan Xu
- Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Li Yang
- Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China; Department of General Surgery, Liyang People's Hospital, Liyang Branch Hospital of Jiangsu Province Hospital, Liyang, Jiangsu Province, China.
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Zhu H, Wu Y, Kang M, Zhang B. MiR-877 suppresses gastric cancer progression by downregulating AQP3. J Int Med Res 2021; 48:300060520903661. [PMID: 32543927 PMCID: PMC7298432 DOI: 10.1177/0300060520903661] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
OBJECTIVES Gastric cancer (GC) is the leading cause of cancer-related deaths worldwide; however, the underlying molecular mechanisms of GC remain unclear. This study investigated the role of the miR-877-AQP3 axis in GC tumorigenesis. METHODS The levels of miR-877 expression were measured in GC tissues and cell lines by qRT-PCR. Functional assays were performed to elucidate the role of miR-877 in GC development. RESULTS Our results showed that miR-877 levels were lower in GC tissues and cell lines compared with the corresponding controls. Additionally, reduced miR-877 levels were associated with unfavorable prognoses. Increased miR-877 expression suppressed proliferation, invasion, and epithelial-mesenchymal transition, while promoting apoptosis in GC cells. Luciferase reporter assays showed that aquaporin 3 (AQP3) was a direct downstream target of miR-877. Overexpression of AQP3 partially rescued the tumor suppressive effects of miR-877 in GC cells. Moreover, miR-877 was negatively correlated with AQP3 mRNA expression in GC tissues. CONCLUSIONS This study demonstrated that miR-877 plays a suppressive role in GC tumorigenesis by regulating AQP3.
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Affiliation(s)
- Hongyu Zhu
- School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| | - Yulian Wu
- Department of General Surgery, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| | - Muxing Kang
- Department of General Surgery, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| | - Bo Zhang
- Department of General Surgery, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
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Comprehensive analysis of tumor mutation burden and immune microenvironment in gastric cancer. Biosci Rep 2021; 41:227672. [PMID: 33492335 PMCID: PMC7921293 DOI: 10.1042/bsr20203336] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2020] [Revised: 01/14/2021] [Accepted: 01/25/2021] [Indexed: 12/13/2022] Open
Abstract
Tumor mutation burden (TMB) was a promising marker for immunotherapy. We aimed to investigate the prognostic role of TMB and its relationship with immune cells infiltration in gastric cancer (GC). We analyzed the mutation landscape of all GC cases and TMB of each GC patient was calculated and patients were divided into TMB-high and TMB-low group. Differentially expressed genes (DEGs) between the two groups were identified and pathway analysis was performed. The immune cells infiltration in each GC patient was evaluated and Kaplan-Meier analysis was performed to investigate the prognostic role of immune cells infiltration. At last, hub immune genes were identified and a TMB prognostic risk score (TMBPRS) was constructed to predict the survival outcome of GC patients. The relationships between mutants of hub immune genes and immune infiltration level in GC was investigated. We found higher TMB was correlated with better survival outcome and female patients, patients with T1-2 and N0 had higher TMB score. Altogether 816 DEGs were harvested and pathway analysis demonstrated that patients in TMB-high group were associated with neuroactive ligand-receptor interaction, cAMP signaling pathway, calcium signaling pathway. The infiltration of activated CD4+ memory T cells, follicular helper T cells, resting NK cells, M0 and M1 macrophages and neutrophils in TMB-high group were higher compared than that in TMB-low group and high macrophage infiltration was correlated with inferior survival outcome of GC patients. Lastly, the TMBPRS was constructed and GC patients with high TMBPRS had poor prognosis.
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Liu Z, Shi M, Li X, Song S, Liu N, Du H, Ye J, Li H, Zhang Z, Zhang L. HER2 copy number as predictor of disease-free survival in HER2-positive resectable gastric adenocarcinoma. J Cancer Res Clin Oncol 2021; 147:1315-1324. [PMID: 33543328 PMCID: PMC8021510 DOI: 10.1007/s00432-021-03522-9] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2020] [Accepted: 01/10/2021] [Indexed: 01/28/2023]
Abstract
Purpose The identification of HER2 overexpression in a subset of gastric adenocarcinoma (GA) patients represents a significant step forward in unveiling the molecular complexity of this disease. The predictive and prognostic value of HER2 amplification in advanced HER2 inhibitor-treated GA patients has been investigated. However, its predictive value in resectable patients remains elusive. Methods We enrolled 98 treatment-naïve resectable Chinese GA patients with HER2 overexpression assessed using IHC. Capture-based targeted sequencing using a panel consisting of 41 gastrointestinal cancer-related genes was performed on tumor tissues. Furthermore, we also investigated the correlation between HER2 copy number (CN) and survival outcomes. Results Of the 98 HER2-overexpressed patients, 90 had HER2 CN amplification assessed using next-generation sequencing, achieving 92% concordance. The most commonly seen concurrent mutations were occurring in TP53, EGFR and PIK3CA. We found HER2 CN as a continuous variable was an independent predictor associated with DFS (p = 0.029). Our study revealed HER2 CN-high patients showed a trend of intestinal-type GA predominant (p = 0.075) and older age (p = 0.07). The median HER2 CN was 15.34, which was used to divide the cohort into CN-high and CN-low groups. Patients with high HER2 CN had a significantly shorter DFS than patients with low HER2 CN (p = 0.002). Furthermore, HER2 CN as a categorical variable was also an independent predictor associated with DFS in patients. Conclusion We elucidated the mutation spectrum of HER2-positive resectable Chinese GA patients and the association between HER2 CN and DFS. Our work revealed HER2 CN as an independent risk factor predicted unfavorable prognosis in HER2-positive GA patients and allowed us to further stratify HER2-positive resectable GA patients for disease management.
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Affiliation(s)
- Zimin Liu
- Oncology Department, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China.
| | - Mingpeng Shi
- Operating Room of Neurosurgery, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China
| | - Xiaoxiao Li
- Oncology Department, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China
| | - Shanai Song
- Oncology Department, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China
| | - Ning Liu
- Oncology Department, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China
| | - Haiwei Du
- Burning Rock Biotech, Guangzhou, China
| | - Junyi Ye
- Burning Rock Biotech, Guangzhou, China
| | - Haiyan Li
- Burning Rock Biotech, Guangzhou, China
| | | | - Lu Zhang
- Burning Rock Biotech, Guangzhou, China
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Shang W, Wang Y, Liang X, Li T, Shao W, Liu F, Cui X, Wang Y, Lv L, Chai L, Qu L, Zheng L, Jia J. SETDB1 promotes gastric carcinogenesis and metastasis via upregulation of CCND1 and MMP9 expression. J Pathol 2021; 253:148-159. [PMID: 33044755 DOI: 10.1002/path.5568] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2020] [Revised: 09/20/2020] [Accepted: 10/07/2020] [Indexed: 12/19/2022]
Abstract
SETDB1 is a histone lysine methyltransferase that has critical roles in cancers. However, its potential role in gastric cancer (GC) remains obscure. Here, we mainly investigate the clinical significance and the possible role of SETDB1 in GC. We find that SETDB1 expression is upregulated in GC tissues and its high-level expression was a predictor of poor prognosis in patients. Overexpression of SETDB1 promoted cell proliferation and metastasis, while SETDB1 suppression had an opposite effect both in vitro and in vivo. Mechanistically, SETDB1 was shown to interact with ERG to promote the transcription of cyclin D1 (CCND1) and matrix metalloproteinase 9 (MMP9) through binding to their promoter regions. In addition, the expression of SETDB1 was also enhanced by the transcription factor TCF4 at the transcriptional level in GC. Furthermore, SETDB1 expression was found to be induced by Helicobacter pylori (H. pylori) infection in a TCF4-dependent manner. Taken together, our results indicate that SETDB1 is aberrantly overexpressed in GC and plays key roles in gastric carcinogenesis and metastasis via upregulation of CCND1 and MMP9. Our work also suggests that SETDB1 could be a potential oncogenic factor and a therapeutic target for GC. © 2020 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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Affiliation(s)
- Wenjing Shang
- Department of Microbiology/Key Laboratory for Experimental Teratology of the Chinese Ministry of Education, School of Basic Medical Science, Cheeloo College of Medicine, Shandong University, Jinan, PR China
- Key Laboratory of Infection and Immunity of Shandong Province, School of Basic Medical Science, Cheeloo College of Medicine, Shandong University, Jinan, PR China
| | - Yue Wang
- Department of Microbiology/Key Laboratory for Experimental Teratology of the Chinese Ministry of Education, School of Basic Medical Science, Cheeloo College of Medicine, Shandong University, Jinan, PR China
| | - Xiuming Liang
- Department of Microbiology/Key Laboratory for Experimental Teratology of the Chinese Ministry of Education, School of Basic Medical Science, Cheeloo College of Medicine, Shandong University, Jinan, PR China
- Shandong University-Karolinska Institute Collaborative Laboratory for Cancer Research, School of Basic Medical Science, Cheeloo College of Medicine, Shandong University, Jinan, PR China
| | - Tongyu Li
- Department of Microbiology/Key Laboratory for Experimental Teratology of the Chinese Ministry of Education, School of Basic Medical Science, Cheeloo College of Medicine, Shandong University, Jinan, PR China
| | - Wei Shao
- Department of Microbiology/Key Laboratory for Experimental Teratology of the Chinese Ministry of Education, School of Basic Medical Science, Cheeloo College of Medicine, Shandong University, Jinan, PR China
| | - Fen Liu
- Department of Microbiology/Key Laboratory for Experimental Teratology of the Chinese Ministry of Education, School of Basic Medical Science, Cheeloo College of Medicine, Shandong University, Jinan, PR China
| | - Xiujie Cui
- Department of Microbiology/Key Laboratory for Experimental Teratology of the Chinese Ministry of Education, School of Basic Medical Science, Cheeloo College of Medicine, Shandong University, Jinan, PR China
| | - Yuanyuan Wang
- Department of Microbiology/Key Laboratory for Experimental Teratology of the Chinese Ministry of Education, School of Basic Medical Science, Cheeloo College of Medicine, Shandong University, Jinan, PR China
| | - Lin Lv
- Department of Microbiology/Key Laboratory for Experimental Teratology of the Chinese Ministry of Education, School of Basic Medical Science, Cheeloo College of Medicine, Shandong University, Jinan, PR China
| | - Li Chai
- Department of Microbiology/Key Laboratory for Experimental Teratology of the Chinese Ministry of Education, School of Basic Medical Science, Cheeloo College of Medicine, Shandong University, Jinan, PR China
| | - Lingxin Qu
- Department of Microbiology/Key Laboratory for Experimental Teratology of the Chinese Ministry of Education, School of Basic Medical Science, Cheeloo College of Medicine, Shandong University, Jinan, PR China
| | - Lixin Zheng
- Department of Microbiology/Key Laboratory for Experimental Teratology of the Chinese Ministry of Education, School of Basic Medical Science, Cheeloo College of Medicine, Shandong University, Jinan, PR China
| | - Jihui Jia
- Department of Microbiology/Key Laboratory for Experimental Teratology of the Chinese Ministry of Education, School of Basic Medical Science, Cheeloo College of Medicine, Shandong University, Jinan, PR China
- Key Laboratory of Infection and Immunity of Shandong Province, School of Basic Medical Science, Cheeloo College of Medicine, Shandong University, Jinan, PR China
- Shandong University-Karolinska Institute Collaborative Laboratory for Cancer Research, School of Basic Medical Science, Cheeloo College of Medicine, Shandong University, Jinan, PR China
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31
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Pourhanifeh MH, Mehrzadi S, Hosseinzadeh A. Melatonin and regulation of miRNAs: novel targeted therapy for cancerous and noncancerous disease. Epigenomics 2020; 13:65-81. [PMID: 33350862 DOI: 10.2217/epi-2020-0241] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
miRNAs, small noncoding RNAs with crucial diagnostic and prognostic capabilities, play essential therapeutic roles in different human diseases. These biomarkers are involved in several biological mechanisms and are responsible for the regulation of multiple genes expressions in cells. miRNA-based therapy has shown a very bright future in the case of clinical interventions. Melatonin, the main product of the pineal gland, is a multifunctional neurohormone with numerous therapeutic potentials in human diseases. Melatonin is able to regulate miRNAs in different pathologies such as malignant and nonmalignant diseases, which can be considered as a novel kind of targeted therapy. Herein, this review discusses possible therapeutic utility of melatonin for the regulation of miRNAs in various pathological conditions.
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Affiliation(s)
| | - Saeed Mehrzadi
- Razi Drug Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Azam Hosseinzadeh
- Razi Drug Research Center, Iran University of Medical Sciences, Tehran, Iran
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32
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Atsumi S, Katoh H, Komura D, Hashimoto I, Furuya G, Koda H, Konishi H, Suzuki R, Yamamoto A, Yuba S, Abe H, Rino Y, Oshima T, Ushiku T, Fukayama M, Seto Y, Ishikawa S. Focal adhesion ribonucleoprotein complex proteins are major humoral cancer antigens and targets in autoimmune diseases. Commun Biol 2020; 3:588. [PMID: 33067514 PMCID: PMC7567837 DOI: 10.1038/s42003-020-01305-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2019] [Accepted: 09/15/2020] [Indexed: 01/06/2023] Open
Abstract
Despite the accumulating evidences of the significance of humoral cancer immunity, its molecular mechanisms have largely remained elusive. Here we show that B-cell repertoire sequencing of 102 clinical gastric cancers and molecular biological analyses unexpectedly reveal that the major humoral cancer antigens are not case-specific neo-antigens but are rather commonly identified as ribonucleoproteins (RNPs) in the focal adhesion complex. These common antigens are shared as autoantigens with multiple autoimmune diseases, suggesting a direct molecular link between cancer- and auto-immunity on the focal adhesion RNP complex. This complex is partially exposed to the outside of cancer cell surfaces, which directly evokes humoral immunity and enables functional bindings of antibodies to cancer cell surfaces in physiological conditions. These findings shed light on humoral cancer immunity in that it commonly targets cellular components fundamental for cytoskeletal integrity and cell movement, pointing to a novel modality of immunotherapy using humoral immunological reactions to cancers.
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Affiliation(s)
- Shinichiro Atsumi
- Department of Preventive Medicine, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan.,Department of Gastrointestinal Surgery, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan
| | - Hiroto Katoh
- Department of Preventive Medicine, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan.
| | - Daisuke Komura
- Department of Preventive Medicine, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan
| | - Itaru Hashimoto
- Department of Preventive Medicine, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan.,Department of Surgery, Yokohama City University, Kanagawa, Japan
| | - Genta Furuya
- Department of Preventive Medicine, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan.,Department of Pathology, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan
| | - Hirotomo Koda
- Department of Preventive Medicine, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan.,Department of Pathology, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan
| | - Hiroki Konishi
- Department of Preventive Medicine, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan
| | - Ryohei Suzuki
- Department of Preventive Medicine, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan
| | - Asami Yamamoto
- Department of Preventive Medicine, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan
| | - Satsuki Yuba
- Department of Preventive Medicine, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan.,Department of Molecular Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan
| | - Hiroyuki Abe
- Department of Pathology, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan
| | - Yasushi Rino
- Department of Surgery, Yokohama City University, Kanagawa, Japan
| | - Takashi Oshima
- Department of Surgery, Yokohama City University, Kanagawa, Japan.,Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Kanagawa, Japan
| | - Tetsuo Ushiku
- Department of Pathology, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan
| | - Masashi Fukayama
- Department of Pathology, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan
| | - Yasuyuki Seto
- Department of Gastrointestinal Surgery, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan
| | - Shumpei Ishikawa
- Department of Preventive Medicine, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan.
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33
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Lu J, Huang XY, Wang YH, Xie JW, Wang JB, Lin JX, Chen QY, Cao LL, Li P, Huang CM, Zheng CH. POC1A acts as a promising prognostic biomarker associated with high tumor immune cell infiltration in gastric cancer. Aging (Albany NY) 2020; 12:18982-19011. [PMID: 33052878 PMCID: PMC7732308 DOI: 10.18632/aging.103624] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2020] [Accepted: 06/04/2020] [Indexed: 01/24/2023]
Abstract
The effect of POC1 centriolar protein A (POC1A) on gastric cancer (GC) has not been clearly defined. In this study, POC1A expression and clinical information in patients with GC were analyzed. Multiple databases were used to investigate the genes that were co-expressed with POC1A and genes whose changes co-occurred with genetic alternations of POC1A. Moreover, the TISIDB and TIMER databases were used to analyze immune infiltration. The GSE54129 GC dataset and LASSO regression model (tumor vs. normal) were employed, and 6 significant differentially expressed genes (LAMP5, CEBPB, ARMC9, PAOX, VMP1, POC1A) were identified. POC1A was selected for its high expression in adjacent tissues, which was confirmed with IHC. High POC1A expression was related to better overall and recurrence-free survival. GO and KEGG analyses demonstrated that POC1A may regulate the cell cycle, DNA replication and cell growth. Furthermore, POC1A was found to be correlated with immune infiltration levels in GC according to the TISIDB and TIMER databases. These findings indicate that POC1A acts as a tumor suppressor in GC by regulating the cell cycle and cell growth. In addition, POC1A preferentially regulates the immune infiltration of GC via several immune genes. However, the specific mechanism requires further study.
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Affiliation(s)
- Jun Lu
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
| | - Xiao-Yan Huang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
| | - Yao-Hui Wang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
| | - Jian-Wei Xie
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
| | - Jia-Bin Wang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
| | - Jian-Xian Lin
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
| | - Qi-Yue Chen
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
| | - Long-Long Cao
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
| | - Ping Li
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
| | - Chang-Ming Huang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
| | - Chao-Hui Zheng
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
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Kawahara Y, Hirashita Y, Tamura C, Kudo Y, Sakai K, Togo K, Fukuda K, Matsunari O, Okamoto K, Ogawa R, Mizukami K, Okimoto T, Kodama M, Murakami K. Helicobacter pylori infection modulates endogenous hydrogen sulfide production in gastric cancer AGS cells. Helicobacter 2020; 25:e12732. [PMID: 32713122 DOI: 10.1111/hel.12732] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2020] [Revised: 06/14/2020] [Accepted: 06/29/2020] [Indexed: 01/11/2023]
Abstract
BACKGROUND Persistent Helicobacter pylori infection induces gastric mucosal atrophy, which is a precancerous condition. Hydrogen sulfide (H2 S), a gaseous biological transmitter, has been implicated in both the physiological functions of the gastrointestinal tract and its diseases. To understand gastric epithelial cell response against H pylori infection, we investigated the metabolic changes of gastric cancer cells co-cultured with H pylori and observed the modulation of endogenous H2 S production. MATERIALS AND METHODS Gastric cancer AGS cells were co-cultured with an H pylori standard strain possessing bacterial virulence factor CagA (ATCC 43504) and a strain without CagA (ATCC 51932). Three hours after inoculation, the cells were subjected to metabolomics analysis using gas chromatography-tandem mass spectrometry (GC-MS/MS). Orthogonal projections to latent structures discriminant analysis (OPLS-DA) and pathway analysis were performed. In addition, intracellular H2 S levels were measured by using HSip-1 fluorescent probe. RESULTS Results of OPLS-DA showed a significant difference between the metabolism of untreated control cells and cells inoculated with the H pylori strains ATCC 51932 or ATCC 43504, mainly due to 45 metabolites. Pathway analysis with the selected metabolites indicated that methionine metabolism, which is related to H2 S production, was the most frequently altered pathway. H pylori-inoculated cells produced more endogenous H2 S than control cells. Moreover, ATCC 43504-inoculated cells produced less H2 S than ATCC 51932-inoculated cells. CONCLUSIONS H pylori infection modulates endogenous H2 S production in AGS cells, suggesting that H2 S might be one of the bioactive molecules involved in the biological mechanisms of gastric mucosal disease including mucosal atrophy.
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Affiliation(s)
- Yoshinari Kawahara
- Department of Gastroenterology, Faculty of Medicine, Oita University, Yufu, Japan
| | - Yuka Hirashita
- Department of Gastroenterology, Faculty of Medicine, Oita University, Yufu, Japan
| | - Chikako Tamura
- Department of Gastroenterology, Faculty of Medicine, Oita University, Yufu, Japan
| | - Yoko Kudo
- Department of Gastroenterology, Faculty of Medicine, Oita University, Yufu, Japan
| | - Kumiko Sakai
- Research Promotion Institute, Faculty of Medicine, Oita University, Yufu, Japan
| | - Kazumi Togo
- Department of Gastroenterology, Faculty of Medicine, Oita University, Yufu, Japan
| | - Kensuke Fukuda
- Department of Gastroenterology, Faculty of Medicine, Oita University, Yufu, Japan
| | - Osamu Matsunari
- Department of Gastroenterology, Faculty of Medicine, Oita University, Yufu, Japan
| | - Kazuhisa Okamoto
- Department of Gastroenterology, Faculty of Medicine, Oita University, Yufu, Japan
| | - Ryo Ogawa
- Department of Gastroenterology, Faculty of Medicine, Oita University, Yufu, Japan
| | - Kazuhiro Mizukami
- Department of Gastroenterology, Faculty of Medicine, Oita University, Yufu, Japan
| | - Tadayoshi Okimoto
- Department of Gastroenterology, Faculty of Medicine, Oita University, Yufu, Japan
| | - Masaaki Kodama
- Department of Gastroenterology, Faculty of Medicine, Oita University, Yufu, Japan
| | - Kazunari Murakami
- Department of Gastroenterology, Faculty of Medicine, Oita University, Yufu, Japan
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Alzeeb G, Metges JP, Corcos L, Le Jossic-Corcos C. Three-Dimensional Culture Systems in Gastric Cancer Research. Cancers (Basel) 2020; 12:E2800. [PMID: 33003476 PMCID: PMC7601358 DOI: 10.3390/cancers12102800] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2020] [Revised: 09/25/2020] [Accepted: 09/27/2020] [Indexed: 12/14/2022] Open
Abstract
Gastric cancer (GC), which includes cancer of the esophagus, the oesophagogastric junction, and the stomach fundus, is highly deadly with strong regional influence, Asia being the most affected. GC is often detected at late stages, with 30% of metastatic cases at diagnosis. Many authors have devised models to both unravel the mechanisms of GC development and to evaluate candidate therapeutics. Among these models, 2D-cell cultures are progressively replaced by 3D-cell cultures that recapitulate, much more comprehensively, tumor cellular and genetic heterogeneity, as well as responsiveness to environmental changes, such as exposure to drugs or irradiation. With respect to the specifics of GC, there are high hopes from such model systems, especially with the aim of identifying prognostic markers and novel drug targets.
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Affiliation(s)
- George Alzeeb
- Inserm, University Brest, EFS, UMR 1078, GGB, F-29200 Brest, France; (G.A.); (L.C.)
| | - Jean-Philippe Metges
- CHU de Brest, Inserm, University Brest, EFS, UMR 1078, GGB, F-29200 Brest, France;
| | - Laurent Corcos
- Inserm, University Brest, EFS, UMR 1078, GGB, F-29200 Brest, France; (G.A.); (L.C.)
- CHU de Brest, Inserm, University Brest, EFS, UMR 1078, GGB, F-29200 Brest, France;
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36
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Nanishi K, Konishi H, Shoda K, Arita T, Kosuga T, Komatsu S, Shiozaki A, Kubota T, Fujiwara H, Okamoto K, Ichikawa D, Otsuji E. Circulating circERBB2 as a potential prognostic biomarker for gastric cancer: An investigative study. Cancer Sci 2020; 111:4177-4186. [PMID: 32896032 PMCID: PMC7648027 DOI: 10.1111/cas.14645] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2020] [Revised: 08/23/2020] [Accepted: 08/30/2020] [Indexed: 01/15/2023] Open
Abstract
Circular RNA is a novel endogenous non‐coding RNA that can serve as a biomarker because of its stable loop structure. We investigated and examined the utility of plasma circERBB2 as a prognostic biomarker in 70 patients with gastric cancer who underwent gastrectomy. We investigated by real‐time quantitative PCR the circERBB2 concentrations in the preoperative and postoperative plasma and the circERBB2 expression in the resected tumors. The relationships between circERBB2 concentration in plasma and the clinicopathological features and prognosis were analyzed. circERBB2 was detected in the preoperative plasma samples of 37 patients. The presence of circERBB2 in preoperative plasma (high group) was significantly correlated with lymph node metastasis (P = .035) and tended to be correlated with men (P = .069). Both relapse‐free and overall survival were significantly poor in the high group (P = .001 and P = .009, respectively). The Cox proportional‐hazard model revealed that the high group was an independent prognostic factor of relapse‐free survival (P = .038). Among 16 patients of the high group, 13 patients did not show circERBB2 in the postoperative plasma. The concentration of circERBB2 in plasma was significantly higher in patients with recurrent cancer than those recurrence‐free patients (P < .001). In 2 patients with recurrent cancer, plasma circERBB2 concentrations were increased, whereas, in 2 recurrence‐free patients, these concentrations hardly changed during the treatment progress. The circERBB2 concentrations in preoperative plasma samples can be considered as a noninvasive prognostic biomarker for gastric cancer. Furthermore, monitoring the postoperative plasma circERBB2 concentrations may be useful for detecting gastric cancer recurrences.
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Affiliation(s)
- Kenji Nanishi
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Hirotaka Konishi
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Katsutoshi Shoda
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan.,First Department of Surgery, Faculty of Medicine, University of Yamanashi, Chuo, Japan
| | - Tomohiro Arita
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Toshiyuki Kosuga
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Shuhei Komatsu
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Atsushi Shiozaki
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Takeshi Kubota
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Hitoshi Fujiwara
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Kazuma Okamoto
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Daisuke Ichikawa
- First Department of Surgery, Faculty of Medicine, University of Yamanashi, Chuo, Japan
| | - Eigo Otsuji
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan
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Kong Q, Zhang Z, Liang Z. Upregulating miR-637 aggravates endoplasmic reticulum stress-induced apoptosis in gastric cancer cells by suppressing Calreticulin. Anim Cells Syst (Seoul) 2020; 24:267-274. [PMID: 33209200 PMCID: PMC7646546 DOI: 10.1080/19768354.2020.1816579] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023] Open
Abstract
Gastric cancer is a leading cause of cancer death worldwide. Endoplasmic reticulum (ER) stress-induced apoptosis has been confirmed to be important in the treatment of gastric cancer. MiR-637 has recently been found to exert inhibitory effects on gastric cancer, and this study aimed to investigate whether miR-637 could regulate apoptosis through ER stress. The results showed that tunicamycin (TM) induced downregulation of miR-637 in gastric cancer cells (AGS) and increase of apoptosis and ER stress. Overexpression of miR-637 promoted TM-induced apoptosis and expression of ER stress associated proteins (GRP78 and CHOP), but inhibited expression of Calreticulin. MiR-637 could bind with the 3'-UTR of CALR, and negatively regulated the expression of CALR. The co-transfection of miR-637 and CALR in AGS cells show that, CALR overexpression could reverse the pro-apoptosis effects of miR-637 in TM-treated cells. In conclusion, the present study suggests that miR-637 participates in ER stress-induced apoptosis in gastric cancer cells by suppressing CALR expression. miR-637 or CALR may be a future potential target for gastric cancer treatment.
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Affiliation(s)
- Qingli Kong
- Department of Hepatobiliary Gastrointestinal Surgery, Tianjin Fourth Central Hospital, The Fourth Central Hospital Affiliated to Nankai University, The Fourth Center Clinical College of Tianjin Medical University, Tianjin City, People's Republic of China
| | - Zhisheng Zhang
- Department of Hepatobiliary Gastrointestinal Surgery, Tianjin Fourth Central Hospital, The Fourth Central Hospital Affiliated to Nankai University, The Fourth Center Clinical College of Tianjin Medical University, Tianjin City, People's Republic of China
| | - Zhipeng Liang
- Department of Hepatobiliary Gastrointestinal Surgery, Tianjin Fourth Central Hospital, The Fourth Central Hospital Affiliated to Nankai University, The Fourth Center Clinical College of Tianjin Medical University, Tianjin City, People's Republic of China
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38
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Guo Q, Xu J, Huang Z, Yao Q, Chen F, Liu H, Zhang Z, Lin J. ADMA mediates gastric cancer cell migration and invasion via Wnt/β-catenin signaling pathway. Clin Transl Oncol 2020; 23:325-334. [PMID: 32607811 PMCID: PMC7854427 DOI: 10.1007/s12094-020-02422-7] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2020] [Accepted: 06/05/2020] [Indexed: 01/05/2023]
Abstract
Objective To explore the role of ADMA in gastric cancer. Methods The specimens of 115 gastric cancer patients were analyzed by ELISA and survival analysis. Functional assays were used to assess the effects of ADMA on gastric cancer cells. Experiments were conducted to detect the signaling pathway induced by ADMA in GC. Results Gastric cancer patients with high ADMA levels had poor prognosis and low survival rate. Furthermore, high level of ADMA did not affect the proliferation while promoted the migration and invasion of gastric cancer cell. Moreover, ADMA enhanced the epithelial–mesenchymal transition (EMT). Importantly, ADMA positively regulated β-catenin expression in GC and promoted GC migration and invasion via Wnt/β-catenin pathway. Conclusions ADMA regulates gastric cancer cell migration and invasion via Wnt/β-catenin signaling pathway and which may be applied to clinical practice as a diagnostic and prognostic biomarker. Electronic supplementary material The online version of this article (10.1007/s12094-020-02422-7) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Q Guo
- Department of Oncological Surgery, The Second Affiliated Hospital of Fujian Medical University, 34 Zhongshanbei Road, Quanzhou, 362000, Fujian, China
| | - J Xu
- Department of Oncological Surgery, The Second Affiliated Hospital of Fujian Medical University, 34 Zhongshanbei Road, Quanzhou, 362000, Fujian, China
| | - Z Huang
- Department of Oncological Surgery, The Second Affiliated Hospital of Fujian Medical University, 34 Zhongshanbei Road, Quanzhou, 362000, Fujian, China
| | - Q Yao
- Department of Oncological Surgery, The Second Affiliated Hospital of Fujian Medical University, 34 Zhongshanbei Road, Quanzhou, 362000, Fujian, China
| | - F Chen
- Department of Oncological Surgery, The Second Affiliated Hospital of Fujian Medical University, 34 Zhongshanbei Road, Quanzhou, 362000, Fujian, China
| | - H Liu
- Department of Oncological Surgery, The Second Affiliated Hospital of Fujian Medical University, 34 Zhongshanbei Road, Quanzhou, 362000, Fujian, China
| | - Z Zhang
- Department of Oncological Surgery, The Second Affiliated Hospital of Fujian Medical University, 34 Zhongshanbei Road, Quanzhou, 362000, Fujian, China
| | - J Lin
- Department of Oncological Surgery, The Second Affiliated Hospital of Fujian Medical University, 34 Zhongshanbei Road, Quanzhou, 362000, Fujian, China.
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Sang NV, Duc NM, Duc PH, Tuan PA. The value of multidetector-row computed tomography in lymph node staging of gastric cancer: a preliminary Vietnamese study. Contemp Oncol (Pozn) 2020; 24:125-131. [PMID: 32774138 PMCID: PMC7403761 DOI: 10.5114/wo.2020.97484] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2020] [Accepted: 06/07/2020] [Indexed: 12/15/2022] Open
Abstract
INTRODUCTION Gastric cancer (GC) is the fourth most common malignant disease in the world, following breast cancer, colorectal cancer, and lung cancer. This study aimed to evaluate the usefulness of multidetector-row computed tomography (MDCT) in identifying the metastatic lymph node of GC. MATERIAL AND METHODS A cross-sectional study was performed after receiving approval by the institutional review board. A total of 88 patients with GC, who underwent radical gastrectomy, were examined by MDCT. Categorical variables were compared using Fisher's exact test. The discriminating ability of lymph node size was determined according to an area under the receiver operating curve(AUROC) analysis, and the optimal cut-off point was determined. RESULTS The proportion of metastatic lymph node patients in the proximal group (32.3%) was significantly higher than that in the distal group (18.4%). T categorisation and lymph node sizes were significantly different between the non-metastatic lymph node and metastatic lymph node groups. The AUROC for lymph node size was 0.738, with an optimal cut-off point of 7.5 mm,producing a sensitivity of 71.5% and a specificity of 70.5%. CONCLUSIONS MDCT displayed medium accuracy for the determination of metastatic lymph nodes and N categorisation. Based on our findings, although MDCT is generally the first choice for preoperative assessments in GC patients, other diagnostic modalities should supplement MDCT in order to achieve more precise N staging.
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Affiliation(s)
- Nguyen Van Sang
- Department of Radiology, Hanoi University of Public Health, Hanoi, Vietnam
| | - Nguyen Minh Duc
- Department of Radiology, Pham Ngoc Thach University of Medicine, Ho Chi Minh City, Vietnam
- Department of Radiology, Children’s Hospital 2, Ho Chi Minh City, Vietnam
| | - Pham Hong Duc
- Department of Radiology, Hanoi Medical University, Hanoi, Vietnam
| | - Phung Anh Tuan
- Department of Radiology, Vietnam Military Medical University, Hanoi, Vietnam
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40
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Wang Z, Li Y, Cao J, Zhang W, Wang Q, Zhang Z, Gao Z, Ye Y, Jiang K, Wang S. MicroRNA Profile Identifies miR-6165 Could Suppress Gastric Cancer Migration and Invasion by Targeting STRN4. Onco Targets Ther 2020; 13:1859-1869. [PMID: 32184620 PMCID: PMC7060782 DOI: 10.2147/ott.s208024] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2019] [Accepted: 02/11/2020] [Indexed: 12/24/2022] Open
Abstract
Background Recent studies showed that aberrant expression of miRNAs causes tumor-suppressing or promoting effects in various cancers including gastric cancer (GC). Our previous studies showed that lots of miRNAs and mRNA expressed differentially in GC and normal tissues. However, the critical miRNAs and mRNA need to be clarified. Materials and Methods Microarray sequencing was used to profile the differential expression of miRNAs and mRNA in GC and normal tissues. Bioinformatics analysis and database prediction were used to search the critical miRNAs and mRNA. Real-time quantitative polymerase chain reaction (RT-qPCR), luciferase reporter assay, immunohistochemistry (IHC), wound healing assay and transwell assay were used to clarify the relationship between the target miRNAs and mRNA. Statistical analysis was used to seek their value of diagnosis and prognosis. Results We identified microRNA-6165 (miR-6165) as a novel cancer-related miRNA in GC through high-throughput microarray sequencing. By bioinformatics analysis and luciferase reporter assay, we found STRN4 was the target of miR-6165. Via a series of cell experiments, we determined that miR-6165 suppressed GC cells migration and invasion by targeting STRN4. Also, we discovered the potential diagnosis and prognosis value of miR-6165 and STRN4. Conclusion It was found that miR-6165 might suppress GC migration and invasion by targeting STRN4 in vitro, and the further research should focus more on the potential diagnosis and prognosis value of miR-6165 and STRN4 in gastric cancer patients.
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Affiliation(s)
- Zhu Wang
- Department of Gastroenterological Surgery, Peking University People's Hospital, Beijing 100044, People's Republic of China.,Laboratory of Surgical Oncology, Beijing Key Laboratory of Colorectal Cancer Diagnosis and Treatment Research, Peking University People's Hospital, Beijing 100044, People's Republic of China
| | - Yang Li
- Department of Gastroenterological Surgery, Peking University People's Hospital, Beijing 100044, People's Republic of China.,Laboratory of Surgical Oncology, Beijing Key Laboratory of Colorectal Cancer Diagnosis and Treatment Research, Peking University People's Hospital, Beijing 100044, People's Republic of China
| | - Jian Cao
- Department of Gastroenterological Surgery, Peking University People's Hospital, Beijing 100044, People's Republic of China
| | - Wei Zhang
- Department of Gastroenterological Surgery, Peking University People's Hospital, Beijing 100044, People's Republic of China.,Laboratory of Surgical Oncology, Beijing Key Laboratory of Colorectal Cancer Diagnosis and Treatment Research, Peking University People's Hospital, Beijing 100044, People's Republic of China
| | - Quan Wang
- Department of Gastroenterological Surgery, Peking University People's Hospital, Beijing 100044, People's Republic of China.,Laboratory of Surgical Oncology, Beijing Key Laboratory of Colorectal Cancer Diagnosis and Treatment Research, Peking University People's Hospital, Beijing 100044, People's Republic of China
| | - Zhen Zhang
- Department of Gastroenterological Surgery, Peking University People's Hospital, Beijing 100044, People's Republic of China.,Laboratory of Surgical Oncology, Beijing Key Laboratory of Colorectal Cancer Diagnosis and Treatment Research, Peking University People's Hospital, Beijing 100044, People's Republic of China
| | - Zhidong Gao
- Department of Gastroenterological Surgery, Peking University People's Hospital, Beijing 100044, People's Republic of China
| | - Yingjiang Ye
- Department of Gastroenterological Surgery, Peking University People's Hospital, Beijing 100044, People's Republic of China.,Laboratory of Surgical Oncology, Beijing Key Laboratory of Colorectal Cancer Diagnosis and Treatment Research, Peking University People's Hospital, Beijing 100044, People's Republic of China
| | - Kewei Jiang
- Department of Gastroenterological Surgery, Peking University People's Hospital, Beijing 100044, People's Republic of China.,Laboratory of Surgical Oncology, Beijing Key Laboratory of Colorectal Cancer Diagnosis and Treatment Research, Peking University People's Hospital, Beijing 100044, People's Republic of China
| | - Shan Wang
- Department of Gastroenterological Surgery, Peking University People's Hospital, Beijing 100044, People's Republic of China.,Laboratory of Surgical Oncology, Beijing Key Laboratory of Colorectal Cancer Diagnosis and Treatment Research, Peking University People's Hospital, Beijing 100044, People's Republic of China
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Chen E, Senders ZJ, Hardacre J, Kim J, Ammori J. Perioperative outcomes and survival of octogenarians undergoing curative resection for esophagogastric adenocarcinoma. J Surg Oncol 2020; 121:1015-1021. [PMID: 32090338 DOI: 10.1002/jso.25866] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2019] [Accepted: 02/07/2020] [Indexed: 12/23/2022]
Abstract
BACKGROUND AND OBJECTIVES Current data are conflicting as to whether the outcomes of octogenarians undergoing resection for esophagogastric adenocarcinoma are comparable to younger patients. This study aims to compare perioperative outcomes and survival of patients ≥80 years old with younger patients undergoing curative resection for esophagogastric adenocarcinoma. METHODS Retrospective data were collected on 190 patients who underwent resection with curative intent for adenocarcinomas found in the stomach and esophagogastric junction from 2004 to 2015 at a single institution. RESULTS Of the 190 patients, 34 (18%) were ≥80 years old. Octogenarians were more likely to have chronic kidney disease (CKD) and were less likely to have received neoadjuvant chemotherapy. Pathologic features were similar between groups. Octogenarians' tumors were more likely to be located in the gastric body as compared to the esophagogastric junction in younger patients. Although the length of stay was comparable, octogenarians were significantly less likely to be discharged home (P < .01). Both groups had a single death during the index admission. Incidence and severity of 90 days postoperative complications were not significantly different between groups. There was no difference in 30-day, 90-day, 1-year, or median survival. CONCLUSIONS Perioperative outcomes and survival of octogenarians undergoing curative resection for esophagogastric cancer are comparable to younger patients at our institution.
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Affiliation(s)
- Eric Chen
- Case Western Reserve University School of Medicine, Cleveland, Ohio
| | - Zachary J Senders
- Department of Surgery, University Hospitals Cleveland Medical Center, Case Western Reserve University, Cleveland, Ohio
| | - Jeffrey Hardacre
- Department of Surgery, University Hospitals Cleveland Medical Center, Case Western Reserve University, Cleveland, Ohio
| | - Julian Kim
- Department of Surgery, University Hospitals Cleveland Medical Center, Case Western Reserve University, Cleveland, Ohio
| | - John Ammori
- Department of Surgery, University Hospitals Cleveland Medical Center, Case Western Reserve University, Cleveland, Ohio
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42
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Cai J, Ding L, Gong P, Huang J. A colorimetric detection of microRNA-148a in gastric cancer by gold nanoparticle-RNA conjugates. NANOTECHNOLOGY 2020; 31:095501. [PMID: 31703221 DOI: 10.1088/1361-6528/ab55b7] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/05/2023]
Abstract
For the early diagnosis of gastric cancer, microRNA-148a (miRNA-148a) as a promising biomarker is measured by a simple colorimetric biosensor due to its unique surface plasmon resonance (SPR) absorption of gold nanoparticles (AuNPs). In the assay system, the sensing probes are facilitated by the conjugation of AuNPs with RNA probes (RNAP) via Au-S bonds, which align in a tail-to-tail fashion onto the target RNA. When miRNA-148a is introduced, a sandwich hybridization reaction is triggered between the AuNP-RNAP conjugates and targets, resulting in changes in the SPR absorption band, microscopic distribution and macroscopic color of the AuNP solution. Following this principle, this colorimetric method is able to quantitatively detect miRNA-148a at nanomolar level with a limit of ∼1.9 nM, and exhibits high sensitivity and selectivity by a low-cost UV-vis spectrometer or even the naked eye. Moreover, the AuNP network materials with a characteristic sharp 'melting transition' provide significant guidance for the reusability of DNA or RNA biosensors.
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Affiliation(s)
- Jun Cai
- National Engineering Laboratory for Fiber Optic Sensing Technology, Wuhan University of Technology, Wuhan, 430070, People's Republic of China
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43
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Huang JY, Xing YN, Wang X, Wang ZN, Hou WB, Yin SC, Xu YY, Zhu Z, Xu HM. The Prognosis Value of Lymphatic Vessel Invasion in pN0 Gastric Cancer Patients with Insufficient Examined Lymph Nodes. J Gastrointest Surg 2020; 24:299-306. [PMID: 30671803 DOI: 10.1007/s11605-018-04101-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2018] [Accepted: 12/29/2018] [Indexed: 01/31/2023]
Abstract
OBJECTIVES To investigate the prognosis value of lymphatic vessel invasion (LVI) in pN0 gastric cancer patients with insufficient examined lymph nodes (ELNs). METHODS Clinicopathologic and prognostic data of pN0 gastric cancer patients with insufficient ELNs who underwent radical surgery in our institution were retrospectively studied. RESULTS Firstly, we confirmed that less than 16 but not less than 30 ELNs were insufficient ELNs in the present study. Of the 350 pN0 patients with < 16 ELNs, 64 patients (18.29%) had LVI. The overall survival (OS) of patients with LVI was significantly poorer than those without LVI. Multivariate analysis suggested that LVI was one of the independent factors predicting prognosis of pN0 patients with < 16 ELNs. Further analyses suggested that there were similar prognoses between pN0 patients with < 16 ELNs who had LVI and pN1 patients, and between pN0 patients with < 16 ELNs who had no LVI and pN0 patients with ≥ 16 ELNs, respectively. Therefore, we proposed a novel pN classification, in which LVI-positive pN0 gastric cancer with < 16 ELNs was classified as pN1 disease. Two-step multivariate analysis demonstrated that the novel pN classification was more suitable for prognostic assessment than the original one. CONCLUSIONS LVI is a powerful and independent prognostic factor for pN0 gastric cancer patients with < 16 ELNs, and node-negative gastric cancer with < 16 ELNs which had LVI should be considered as node-positive disease. LVI is an effective indicator identifying patients stage migration happens to in pN0 patients with < 16 ELNs.
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Affiliation(s)
- Jin-Yu Huang
- Department of Surgical Oncology, First Affiliated Hospital of China Medical University, Shenyang, 110001, Liaoning, China
| | - Ya-Nan Xing
- Department of Surgical Oncology, First Affiliated Hospital of China Medical University, Shenyang, 110001, Liaoning, China
| | - Xin Wang
- Department of Surgical Oncology, First Affiliated Hospital of China Medical University, Shenyang, 110001, Liaoning, China
| | - Zhen-Ning Wang
- Department of Surgical Oncology, First Affiliated Hospital of China Medical University, Shenyang, 110001, Liaoning, China
| | - Wen-Bin Hou
- Department of Surgical Oncology, First Affiliated Hospital of China Medical University, Shenyang, 110001, Liaoning, China
| | - Song-Cheng Yin
- Department of Surgical Oncology, First Affiliated Hospital of China Medical University, Shenyang, 110001, Liaoning, China
| | - Ying-Ying Xu
- Department of Breast Surgery, First Affiliated Hospital of China Medical University, Shenyang, China
| | - Zhi Zhu
- Department of Surgical Oncology, First Affiliated Hospital of China Medical University, Shenyang, 110001, Liaoning, China
| | - Hui-Mian Xu
- Department of Surgical Oncology, First Affiliated Hospital of China Medical University, Shenyang, 110001, Liaoning, China.
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Germacrone exerts anti-cancer effects on gastric cancer through induction of cell cycle arrest and promotion of apoptosis. BMC Complement Med Ther 2020; 20:21. [PMID: 32020876 PMCID: PMC7076853 DOI: 10.1186/s12906-019-2810-3] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2019] [Accepted: 12/24/2019] [Indexed: 12/12/2022] Open
Abstract
Background Germacrone is one of the natural bioactive compounds found in Rhizoma curcuma essential oils. In this study, the potential anti-cancer effect of germacrone in gastric cancer cell line BGC823 was investigated. Methods The cell viability and proliferative activity were assessed, and cell cycle analysis was also performed. Hoechst 33258 and Annexin V/PI double staining was used for detection of cell apoptosis. Protein profiles of cell cycle-related and apoptosis-related proteins were assessed. Results MTT assay revealed that germacrone had marked cytotoxicity on BGC823 cells. Germacrone induced cell cycle arrest in the G2/M phase via remarkably decreased expression levels of cyclin B1, cdc 2 and cdc 25c. In addition, the treatment with germacrone induced caspase-3 activity and PARP cleavage. These findings demonstrated the effects of germacrone on inhibiting cell proliferation through induction of G2/M phase cell cycle arrest and promotion of cell apoptosis. It also indicated that germacrone functioned through modulations of cell cycle-associated protein expression and mitochondria-mediated apoptosis. Conclusion These findings will be valuable as the molecular basis for the germacrone-mediated anti-cancer effect against gastric cancer.
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45
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Cai JS, Chen HY, Chen JY, Lu YF, Sun JZ, Zhou Y, Yu RS. Reduced field-of-view diffusion-weighted imaging (DWI) in patients with gastric cancer: Comparison with conventional DWI techniques at 3.0T: A preliminary study. Medicine (Baltimore) 2020; 99:e18616. [PMID: 31895817 PMCID: PMC6946437 DOI: 10.1097/md.0000000000018616] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
To evaluate the qualitative image quality and quantitative apparent diffusion coefficient (ADC) value of reduced field-of view (rFOV) and full field-of-view (fFOV) diffusion-weighted imaging (DWI) sequences at 3.0 T in patients with gastric cancer.Fifty-three patients (37 males, 16 females; mean age, 63.3 ± 10.3 years) with 60 lesions with gastric cancer who underwent magnetic resonance (MR) scans, including both rFOV-DWI and fFOV-DWI, were retrospectively analyzed. Two observers subjectively evaluated image quality for both the fFOV-DWI and rFOV-DWI sequences regarding the anatomic details, distortion, lesion conspicuity, artifacts, and overall image quality. The mean ADC values of gastric cancer were calculated. The Wilcoxon test and paired samples t test were used. Interobserver agreement was assessed using kappa statistics.The mean scores based on the 2 observers demonstrated significant differences in image quality in terms of anatomic details, distortion, lesion conspicuity, artifacts and overall image quality at both b values between rFOV-DWI and fFOV-DWI (P < .05) in the whole gastric area. rFOV-DWI yielded significantly better scores in image quality at b = 800 seconds/mm (P < .05) in patients with esophagogastric junction cancers, but there were no significant differences in the gastric corpus and gastric antrum region. The mean tumor ADC values of rFOV-DWI were significantly lower than those of fFOV-DWI (1.237 ± 0.228 × 10-3 mm/second vs 1.683 ± 0.322 × 10-3 mm/second, P < .001).rFOV-DWI yielded significantly better image quality (anatomic details, distortion, lesion conspicuity, artifacts, overall image quality) and more accurate ADC measurements than fFOV-DWI did.
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Affiliation(s)
| | | | | | | | | | - Ying Zhou
- Department of Neurology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
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46
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Xu W, Zhou B, Wu J, Jiang P, Chen H, Yan F. Circular RNA hsa-circ-0007766 modulates the progression of Gastric Carcinoma via miR-1233-3p/ GDF15 axis. Int J Med Sci 2020; 17:1569-1583. [PMID: 32669960 PMCID: PMC7359391 DOI: 10.7150/ijms.46261] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2020] [Accepted: 06/12/2020] [Indexed: 12/14/2022] Open
Abstract
Circular RNAs (circRNAs), a new kind of non-coding RNAs, have gradually been proved to be critical regulators of gene expression; however, the underlying mechanisms still need to be elaborated. In the present study, we investigated the role of hsa-circ-0007766 in gastric carcinoma (GC). Quantitative real-time PCR was applied to detect the differential expression levels of circRNA, miRNAs, and mRNAs in human tissues and specific cell lines. GC cell lines were transiently transfected with siRNA. Then the proliferation, migration, and invasion assays were performed to evaluate the effect of hsa-circ-0007766 in GC cell lines. Fluorescence in situ hybridization, RNA pulldown assay was used to confirm the location of hsa-circ-0007766 and its relationship with miR-1233-3p. Luciferase reporter assay was then conducted to verify the interaction between miR-1233-3p and GDF15. Interestingly, we found that hsa-circ-0007766 was highly expressed in human GC tissues and GC cell lines. Knock-down of hsa-circ-0007766 inhibited cell proliferation, migration, invasion, and down-regulated the expression of GDF15. Moreover, hsa-circ-0007766 was identified as a sponge of miR-1233-3p, which could target gene GDF15 to regulate the progression of GC. Finally, hsa-circ-0007766 was evaluated to be a valuable diagnostic marker with a sensitivity of 53.33% and specificity of 83.33% by ROC analysis. This study unveils a mechanism by which hsa-circ-0007766 regulates GDF15 via hsa-circ-0007766/miR-1233-3p/GDF15 axis, which may provide new insight for GC therapeutic strategies.
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Affiliation(s)
- Weiguo Xu
- Department of General Surgery, The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing 210009, China
| | - Bin Zhou
- Department of General Surgery, The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing 210009, China
| | - Jun Wu
- Department of Clinical Laboratory, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing 210009, China
| | - Pan Jiang
- Department of Clinical Laboratory, The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing 210009, China
| | - Huanqiu Chen
- Department of General Surgery, The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing 210009, China
| | - Feng Yan
- Department of Clinical Laboratory, The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing 210009, China
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Liang X, Zhu J, Li Y, Xu Y, Chen K, Lv L, Mao W. Treatment strategies for metastatic gastric cancer: chemotherapy, palliative surgery or radiotherapy? Future Oncol 2019; 16:91-102. [PMID: 31868545 DOI: 10.2217/fon-2019-0495] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Aim: This study explored whether chemotherapy combined with palliative surgery and/or radiotherapy is a possible treatment for metastatic gastric cancer. Materials & methods: Patients were divided into groups according to treatments. COX models were used to explore prognostic factors. Kaplan-Meier models and log-rank tests were used to analyze outcomes. Outcomes were analyzed before and after propensity score matching. Results: Chemotherapy combined with gastrectomy or metastasectomy prolongs the survival time compared with chemotherapy alone (p < 0.05). Chemotherapy combined with gastrectomy plus metastasectomy and/or radiation therapy also prolongs the survival time (p < 0.05). Conclusion: Chemotherapy combined with gastrectomy could be a more effective treatment for metastatic gastric cancer. Chemotherapy combined with gastrectomy plus metastasectomy and/or radiation therapy could also be a promising treatment.
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Affiliation(s)
- Xiao Liang
- Department of Oncology, Jiangyin People's Hospital, Jiangyin, Jiangsu, PR China
| | - Jiamin Zhu
- Department of Oncology, Jiangyin People's Hospital, Jiangyin, Jiangsu, PR China
| | - Yuanye Li
- Department of Infection Management, Jining No.1 People's Hospital, Jining, Shandong, PR China
| | - Yiren Xu
- Nantong University, Nantong, Jiangsu, PR China
| | - Kai Chen
- Department of Oncology, Affiliated Hospital of Nantong University, Nantong, Jiangsu, PR China.,Nantong University, Nantong, Jiangsu, PR China
| | - Liting Lv
- Department of Oncology, Affiliated Hospital of Nantong University, Nantong, Jiangsu, PR China.,Nantong University, Nantong, Jiangsu, PR China
| | - Weidong Mao
- Department of Oncology, Jiangyin People's Hospital, Jiangyin, Jiangsu, PR China
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Feng C, She J, Chen X, Zhang Q, Zhang X, Wang Y, Ye J, Shi J, Tao J, Feng M, Guan W, Xia H, Zhang W, Xu G. Exosomal miR-196a-1 promotes gastric cancer cell invasion and metastasis by targeting SFRP1. Nanomedicine (Lond) 2019; 14:2579-2593. [PMID: 31609675 DOI: 10.2217/nnm-2019-0053] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023] Open
Abstract
Aim: To investigate the role of exosomal miRNAs on gastric cancer (GC) metastasis. Materials & methods: miRNA expression profiles of exosomes with distinct invasion potentials were analyzed using miRNA microarray and validated by quantitative real-time PCR. In vitro and in vivo experiments assessed the role of exosomal miR-196a-1 in GC's metastasis. Results: High expression level of exosomal miR-196a-1 expression was significantly associated with poor survival in GC. Exosomes that contained miR-196a-1 were secreted from high-invasive GC cells. Ectopic miR-196a-1 expression promoted invasion of low-invasive GC cells by targeting SFRP1. Conclusion: miR-196a-1 was delivered from high-invasive GC into low-invasive GC cells via exosomes and promoted metastasis to the liver in vitro and in vivo.
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Affiliation(s)
- Chun Feng
- Department of Gastroenterology, The Third People's Hospital of Bengbu, Bengbu, 233000, PR China
| | - Junjun She
- Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China
| | - Xiaobing Chen
- Department of Oncology, Henan Cancer Hospital, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou 450008, PR China
| | - Qunchao Zhang
- Department of Gastroenterology, The Third People's Hospital of Bengbu, Bengbu, 233000, PR China
| | - Xu Zhang
- Department of Gastroenterology, The Third People's Hospital of Bengbu, Bengbu, 233000, PR China
| | - Yongsheng Wang
- Department of Respiratory Medicine, Nanjing Drum Tower Hospital affiliated to Medical School of Nanjing University, Nanjing 210008, PR China
| | - Jiahui Ye
- Department of General Surgery, Nanjing Drum Tower Hospital affiliated to Medical School of Nanjing University, Nanjing 210008, PR China
| | - Jiajun Shi
- Department of General Surgery, Nanjing Drum Tower Hospital affiliated to Medical School of Nanjing University, Nanjing 210008, PR China
| | - Jinqiu Tao
- Department of General Surgery, Nanjing Drum Tower Hospital affiliated to Medical School of Nanjing University, Nanjing 210008, PR China
| | - Min Feng
- Department of General Surgery, Nanjing Drum Tower Hospital affiliated to Medical School of Nanjing University, Nanjing 210008, PR China
| | - Wenxian Guan
- Department of General Surgery, Nanjing Drum Tower Hospital affiliated to Medical School of Nanjing University, Nanjing 210008, PR China
| | - Hongping Xia
- Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China.,Department of Pathology, School of Basic Medical Sciences & The Affiliated Sir Run Run Hospital & State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 211166, PR China
| | - Weijie Zhang
- Department of General Surgery, Nanjing Drum Tower Hospital affiliated to Medical School of Nanjing University, Nanjing 210008, PR China
| | - Guifang Xu
- Department of Gastroenterology, Nanjing Drum Tower Hospital affiliated to Medical School of Nanjing University, Nanjing 210008, PR China
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Molecular Profiles and Metastasis Markers in Chinese Patients with Gastric Carcinoma. Sci Rep 2019; 9:13995. [PMID: 31570735 PMCID: PMC6769015 DOI: 10.1038/s41598-019-50171-7] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2018] [Accepted: 09/06/2019] [Indexed: 02/08/2023] Open
Abstract
The goal of this work was to investigate the molecular profiles and metastasis markers in Chinese patients with gastric carcinoma (GC). In total, we performed whole exome sequencing (WES) on 74 GC patients with tumor and adjacent normal formalin-fixed, paraffin-embedded (FFPE) tissue samples. The mutation spectrum of these samples showed a high concordance with TCGA and other studies on GC. PTPRT is significantly associated with metastasis of GC, suggesting its predictive role in metastasis of GC. Patients carrying BRCA2 mutations tend not to metastasize, which may be related to their sensitivity to chemotherapy. Mutations in MACF1, CDC27, HMCN1, CDH1 and PDZD2 were moderately enriched in peritoneal metastasis (PM) samples. Furthermore, we found two genomic regions (1p36.21 and Xq26.3) were associated with PM of GC, and patients with amplification of 1p36.21 and Xq26.3 have a worse prognosis (P = 0.002, 0.01, respectively). Our analysis provides GC patients with potential markers for single and combination therapies.
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50
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Kim IH. Current status of adjuvant chemotherapy for gastric cancer. World J Gastrointest Oncol 2019; 11:679-685. [PMID: 31558973 PMCID: PMC6755106 DOI: 10.4251/wjgo.v11.i9.679] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2019] [Revised: 07/18/2019] [Accepted: 08/21/2019] [Indexed: 02/05/2023] Open
Abstract
Although radical gastrectomy is a standard treatment for advanced gastric cancer, recurrence remains high. After several large-scale controlled studies have shown the beneficial effects of adjuvant chemotherapy, that treatment emerged as a standard option for advanced gastric cancer after gastrectomy. However, various guidelines from different countries have suggested different adjuvant chemotherapies. Understanding the differences between guidelines is very important for investigating further therapeutic strategies. Fortunately, because there are many ongoing studies about new regimens for adjuvant treatment, it is expected that patients with gastric cancer after surgery will have better outcome.
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Affiliation(s)
- In-Hwan Kim
- Department of Surgery, Catholic University of Daegu, Daegu 42472, South Korea
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