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Morita R, Sugeta S, Yoshida J, Ueda T, Hara T, Morimoto Y, Shibuya A, Ohno T, Nakajima T, Fuji N, Konishi E, Yoshida N. Primary Neuroendocrine Carcinoma of the Anal Canal with Cancer Genome Profiling. Intern Med 2025; 64:1350-1354. [PMID: 39401914 DOI: 10.2169/internalmedicine.4289-24] [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] [Indexed: 05/02/2025] Open
Abstract
Primary neuroendocrine carcinoma (NEC) of the anal canal is a rare, highly malignant tumor with a poor prognosis. Despite the standard first-line treatment with etoposide or irinotecan combined with cisplatin, effective second-line therapies are lacking. In 2019, Japan approved cancer genome profiling (CGP) tests for solid tumors to enhance genomic understanding. We present the case of a 79-year-old woman with NEC of the anal canal, treated with etoposide, carboplatin, and amrubicin. As Post-standard therapy, CGP suggested pemigatinib, a tyrosine kinase inhibitor; however, the patient died before receiving it. This case highlights the potential of personalized medicine to improve outcomes in such cases.
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Affiliation(s)
- Ryuichi Morita
- Department of Gastroenterology and Hepatology, Kyoto Saiseikai Hospital, Japan
| | - Seiya Sugeta
- Department of Gastroenterology and Hepatology, Kyoto Saiseikai Hospital, Japan
| | - Juichiro Yoshida
- Department of Gastroenterology and Hepatology, Japanese Red Cross Society Kyoto Daiichi Hospital, Japan
| | - Tomohiro Ueda
- Department of Gastroenterology and Hepatology, Kyoto Saiseikai Hospital, Japan
| | - Tasuku Hara
- Department of Gastroenterology and Hepatology, Kyoto Saiseikai Hospital, Japan
| | - Yasutaka Morimoto
- Department of Gastroenterology and Hepatology, Kyoto Saiseikai Hospital, Japan
| | - Akiko Shibuya
- Department of Gastroenterology and Hepatology, Kyoto Saiseikai Hospital, Japan
| | - Tomoyuki Ohno
- Department of Gastroenterology and Hepatology, Kyoto Saiseikai Hospital, Japan
| | - Tomoki Nakajima
- Department of Gastroenterology and Hepatology, Kyoto Saiseikai Hospital, Japan
| | - Nobuaki Fuji
- Department of Digestive Surgery, Kyoto Saiseikai Hospital, Japan
| | - Eiichi Konishi
- Department of Surgical Pathology, Kyoto Prefectural University of Medicine, Japan
| | - Norimasa Yoshida
- Department of Gastroenterology and Hepatology, Kyoto Saiseikai Hospital, Japan
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2
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Li S, Geng S, Chen Y, Ren Q, Luan Y, Liang W, Chang Y, Zhang L, Zhu D, Wu W, Zhang Y, Zhang L, Wang Y, Zhong G, Wei B, Ma J, Chang Y, Wang X, Li Z, Duan C, Long G, Mao M. Clinical Validation of a Noninvasive Multi-Omics Method for Multicancer Early Detection in Retrospective and Prospective Cohorts. J Mol Diagn 2025:S1525-1578(25)00106-0. [PMID: 40311780 DOI: 10.1016/j.jmoldx.2025.04.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2024] [Revised: 03/04/2025] [Accepted: 04/04/2025] [Indexed: 05/03/2025] Open
Abstract
Recent studies highlight the promise of blood-based multicancer early detection (MCED) tests for identifying asymptomatic patients with cancer. However, most focus on a single cancer hallmark, thus limiting effectiveness because of cancer's heterogeneity. Here, a blood-based multi-omics test named SeekInCare for MCED is reported. SeekInCare incorporates multiple genomic and epigenetic hallmarks, including copy number aberration, fragment size, end motif, and oncogenic virus, via shallow whole-genome sequencing from cell-free DNA, alongside seven protein tumor markers in one tube of blood. Artificial intelligence algorithms were developed to distinguish patients with cancer from individuals without cancer and to predict the likely affected organ. The retrospective study included 617 patients with cancer and 580 individuals without cancer, covering 27 cancer types. SeekInCare achieved 60.0% sensitivity at 98.3% specificity, resulting in an area under the curve of 0.899. Sensitivities were 37.7%, 50.4%, 66.7%, and 78.1% in patients with stage I, II, III, and IV disease, respectively. Additionally, SeekInCare was evaluated in a prospective cohort consisting of 1203 individuals who received the test as a laboratory-developed test (median follow-up time, 753 days) in which it achieved 70.0% sensitivity at 95.2% specificity. The performances of SeekInCare in both retrospective and prospective studies demonstrate that SeekInCare is a blood-based MCED test, showing comparable performance to the other tests currently in development. These findings support its potential clinical utility as a cancer screening test in high-risk populations.
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Affiliation(s)
- Shiyong Li
- Research and Development, SeekIn Inc., Shenzhen, China
| | | | - Yan Chen
- Research and Development, SeekIn Inc., Shenzhen, China
| | - Qingqi Ren
- Department of Oncology, Peking University Shenzhen Hospital, Shenzhen, China
| | - Yi Luan
- Department of Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Weijie Liang
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Yinyin Chang
- Clinical Laboratories, Shenyou Bio, Zhengzhou, China
| | - Lijuan Zhang
- Clinical Laboratories, Shenyou Bio, Zhengzhou, China
| | - Dandan Zhu
- Clinical Laboratories, Shenyou Bio, Zhengzhou, China
| | - Wei Wu
- Research and Development, SeekIn Inc., Shenzhen, China
| | - Yingying Zhang
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Linfeng Zhang
- Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Yan Wang
- Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Guolin Zhong
- Research and Development, SeekIn Inc., Shenzhen, China
| | - Bing Wei
- Department of Molecular Pathology, Henan Cancer Hospital, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China
| | - Jie Ma
- Department of Molecular Pathology, Henan Cancer Hospital, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China
| | - Yu Chang
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Xinhua Wang
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Zhiming Li
- Department of Internal Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Chaohui Duan
- Department of Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Guanghui Long
- Department of Oncology, Peking University Shenzhen Hospital, Shenzhen, China
| | - Mao Mao
- Research and Development, SeekIn Inc., San Diego, California; Yonsei Song-Dang Institute for Cancer Research, Yonsei University, Seoul, Republic of Korea.
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3
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Fang Y, Zhang X, Guo Y, Dong Y, Liu W, Hu X, Li X, Gao D. PKMYT1: A Potential Target for CCNE1 Amplificated Colorectal Tumors. Cell Biochem Biophys 2023; 81:569-576. [PMID: 37572218 DOI: 10.1007/s12013-023-01158-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2022] [Accepted: 07/31/2023] [Indexed: 08/14/2023]
Abstract
Colorectal cancer is a malignant tumor with higher morbidity and mortality. The purpose of this study is to investigate whether inhibition of Protein Kinase, Membrane Associated Tyrosine/Threonine 1 (PKMYT1) affects tumor cell proliferation, survival and migration in colon tumors with high Cyclin E1 (CCNE1) expression. PcDNA3.1-CCNE1 vector and si-PKMYT1 were transfected in SW480 cells by Lipofectamine 2000. Q-PCR and western blot assay were processed to detect the expression. Transwell assay and Edu assay were undertaken to verify the migration and proliferation. CCNE1 promotes the proliferation and migration of SW480. Silencing of PKMYT1 inhibited the proliferation of tumor cells. Silencing the expression of PKMYT1 under the premise of overexpression of CCNE1, the level of Cyclin Dependent Kinase 1 (CDK1)-PT14 was reduced, indicating that the cell cycle was blocked. The expression of γH2AX increased significantly, indicating that the DDR pathway of tumor cells was activated and DNA damage accumulated. The results of immunofluorescence microscopy showed significantly increased expression of DNA damage-associated marker (γH2AX: H2AX Variant Histone). In CCNE1 amplificated colorectal tumor cells, knockdown of PKMYT1 reduced cells in S phase, inhibited cell proliferation and promoted cell apoptosis, confirming that PKMYT1 was a potential therapeutic target for colorectal tumor. This study may verify a potential therapeutic target and provide a new idea for the treatment of colorectal cancer in the future.
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Affiliation(s)
- Yong Fang
- Department of General Surgery, The 305 hospital of People's Liberation Army, Beijing, 100017, China
| | - Xuhui Zhang
- Department of Anesthesiology, The 305 hospital of People's Liberation Army, Beijing, 100017, China
| | - Yuyang Guo
- Department of General Surgery, The 305 hospital of People's Liberation Army, Beijing, 100017, China
| | - Yi Dong
- Department of General Surgery, The 305 hospital of People's Liberation Army, Beijing, 100017, China
| | - Wenfei Liu
- Department of General Surgery, The 305 hospital of People's Liberation Army, Beijing, 100017, China
| | - Xihua Hu
- Department of General Surgery, The 305 hospital of People's Liberation Army, Beijing, 100017, China
| | - Xuxin Li
- Department of General Surgery, The 305 hospital of People's Liberation Army, Beijing, 100017, China
| | - Daifeng Gao
- Department of Health, Guard Bureau of the Joint Staff of the Central Military Commission, Beijing, 100013, China.
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Pessôa R, de Souza DRV, Nukui Y, Pereira J, Fernandes LA, Marcusso RN, de Oliveira ACP, Casseb J, da Silva Duarte AJ, Sanabani SS. Small RNA Profiling in an HTLV-1-Infected Patient with Acute Adult T-Cell Leukemia-Lymphoma at Diagnosis and after Maintenance Therapy: A Case Study. Int J Mol Sci 2023; 24:10643. [PMID: 37445821 DOI: 10.3390/ijms241310643] [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: 06/01/2023] [Revised: 06/22/2023] [Accepted: 06/23/2023] [Indexed: 07/15/2023] Open
Abstract
Small RNAs (sRNAs) are epigenetic regulators of essential biological processes associated with the development and progression of leukemias, including adult T-cell leukemia/lymphoma (ATLL) caused by human T-cell lymphotropic virus type 1 (HTLV-1), an oncogenic human retrovirus originally discovered in a patient with adult T-cell leukemia/lymphoma. Here, we describe the sRNA profile of a 30-year-old woman with ATLL at the time of diagnosis and after maintenance therapy with the aim of correlating expression levels with response to therapy.
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Affiliation(s)
- Rodrigo Pessôa
- Postgraduate Program in Translational Medicine, Department of Medicine, Federal University of São Paulo (UNIFESP), São Paulo 04039-002, Brazil
| | - Daniela Raguer Valadão de Souza
- Postgraduate Program in Translational Medicine, Department of Medicine, Federal University of São Paulo (UNIFESP), São Paulo 04039-002, Brazil
| | - Youko Nukui
- Department of Hematology, Faculty of Medicine, University of São Paulo, São Paulo 05403-000, Brazil
| | - Juliana Pereira
- Department of Hematology, Faculty of Medicine, University of São Paulo, São Paulo 05403-000, Brazil
| | - Lorena Abreu Fernandes
- Postgraduate Program in Translational Medicine, Department of Medicine, Federal University of São Paulo (UNIFESP), São Paulo 04039-002, Brazil
| | - Rosa Nascimento Marcusso
- Department of Neurology, Emilio Ribas Institute of Infectious Diseases, São Paulo 01246-900, Brazil
| | | | - Jorge Casseb
- Laboratory of Medical Investigation LIM-56, Division of Dermatology, Medical School, University of São Paulo, São Paulo 05403-000, Brazil
| | - Alberto José da Silva Duarte
- Laboratory of Medical Investigation LIM-56, Division of Dermatology, Medical School, University of São Paulo, São Paulo 05403-000, Brazil
| | - Sabri Saeed Sanabani
- Laboratory of Medical Investigation LIM-56, Division of Dermatology, Medical School, University of São Paulo, São Paulo 05403-000, Brazil
- Laboratory of Medical Investigation Unit 03, Clinics Hospital, Faculty of Medicine, University of São Paulo, São Paulo 05403-000, Brazil
- Laboratory of Dermatology and Immunodeficiency, LIM56/03, Instituto de Medicina Tropical de São Paulo Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Eneas de Carvalho Aguiar, 470 3° andar, São Paulo 05403-000, Brazil
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5
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Kwon HJ, Park Y, Nam SK, Kang E, Kim KK, Jeong I, Kwak Y, Yoon J, Kim TY, Lee KW, Oh DY, Im SA, Kong SH, Park DJ, Lee HJ, Kim HH, Yang HK, Lee HS. Genetic and immune microenvironment characterization of HER2-positive gastric cancer: Their association with response to trastuzumab-based treatment. Cancer Med 2023; 12:10371-10384. [PMID: 36916290 DOI: 10.1002/cam4.5769] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2022] [Revised: 02/07/2023] [Accepted: 02/22/2023] [Indexed: 03/16/2023] Open
Abstract
BACKGROUND We aimed to determine the molecular and immune microenvironment characteristics of HER2-positive gastric cancer (GC) related to the patient's response to first-line trastuzumab-based treatment. METHODS Eighty-three cases of HER2-positive advanced gastric adenocarcinoma patients treated with trastuzumab were enrolled. Targeted deep sequencing and transcriptome analysis were performed on selected 21 cases (exploration cohort) along with two post-treatment samples. The results were compared between patients progressed before 6 months (Group 2) and others (Group 1), and were validated by FISH and immunohistochemistry in total cohort. Tumor-infiltrating immune cells were evaluated using RNA sequencing data and multiplex immunohistochemistry. Progression-free survival (PFS) analysis was performed. RESULTS Group 1 showed frequent amplification of G1/S cell cycle checkpoint-related genes and upregulated KEGG pathways related to cell proliferation. In contrast, Group 2 had more frequent EGFR, HER3, and MET amplification and higher RNA expression in immune-related KEGG pathways than Group 1. In total cohort, significant predictors of better PFS were cell cycle-related including CCNE1 amplification, Cyclin A and PLK1 overexpression, and decreased Cyclin D3 and HER3 expression (p < 0.05), or immune-related including high density of CD3- CD57+ NK cells and PD-L1 combined positive score ≥5 (p < 0.05). The best prognostic predictors were a combination of Cyclin A, Cyclin E, p21, and HER3 (p < 0.001). CONCLUSION HER2-positive GC with favorable response to trastuzumab were characterized by cell cycle-related gene alterations and increased CD3- CD57+ NK cell infiltration. These findings would be helpful to the fine modulation of therapeutic strategies for patients with HER2-positive GC.
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Affiliation(s)
- Hyun Jung Kwon
- Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
| | - Yujun Park
- Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
| | - Soo Kyung Nam
- Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.,Cancer Research Institute, Seoul National University, Seoul, Republic of Korea.,Integrated Major in Innovative Medical Science, Seoul National University Graduate School, Seoul, Republic of Korea
| | - Enoch Kang
- Seoul National University College of Medicine, Seoul, Republic of Korea
| | | | | | - Yoonjin Kwak
- Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jeesun Yoon
- Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Tae-Yong Kim
- Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Keun-Wook Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Do-Youn Oh
- Cancer Research Institute, Seoul National University, Seoul, Republic of Korea.,Integrated Major in Innovative Medical Science, Seoul National University Graduate School, Seoul, Republic of Korea.,Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Seock-Ah Im
- Cancer Research Institute, Seoul National University, Seoul, Republic of Korea.,Integrated Major in Innovative Medical Science, Seoul National University Graduate School, Seoul, Republic of Korea.,Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Seong-Ho Kong
- Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Do Joong Park
- Cancer Research Institute, Seoul National University, Seoul, Republic of Korea.,Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Hyuk-Joon Lee
- Cancer Research Institute, Seoul National University, Seoul, Republic of Korea.,Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Hyung-Ho Kim
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Han-Kwang Yang
- Cancer Research Institute, Seoul National University, Seoul, Republic of Korea.,Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Hye Seung Lee
- Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.,Cancer Research Institute, Seoul National University, Seoul, Republic of Korea
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6
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Xu L, Chen X, Jiang H, Xu J, Wang L, Sun Y. NDUFC1 Is Upregulated in Gastric Cancer and Regulates Cell Proliferation, Apoptosis, Cycle and Migration. Front Oncol 2021; 11:709044. [PMID: 34966665 PMCID: PMC8710466 DOI: 10.3389/fonc.2021.709044] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2021] [Accepted: 11/04/2021] [Indexed: 01/13/2023] Open
Abstract
Gastric cancer is one of the most common primary tumors of the digestive system. NADH: ubiquinone oxidoreductase subunit C1 (NDUFC1), which is an accessory subunit of the NADH dehydrogenase (complex I), is responsible for the transportation of electrons from NADH to the respiratory chain essential for the oxidative phosphorylation. However, little is known about the roles of NDUFC1 in carcinogenesis. In this study, NDUFC1 protein level in NSCLC tissues was tested by immunohistochemistry (IHC) staining. NDUFC1 mRNA level in gastric cancer cell lines was determined by qRT-PCR. MGC-803 and SGC-7901 cells were transfected with shNDUFC1 lentivirus designed to silence NDUFC1. MTT assay, CCK8 assay, wound healing assay and transwell migration assay were conducted. Cell cycle and apoptosis were detected by flow cytometry. In vivo experiments were performed using nude mice. The results indicated that overexpressed NDUFC1 in gastric cancer was related to more serious tumor infiltrates, a higher risk of lymphatic metastasis, a higher proportion of positive lymph nodes, and a more advanced tumor stage. Compared with shCtrl groups, MGC-803 and SGC-7901 of shNDUFC1 groups had lower abilities of proliferation and migration, higher levels of apoptosis. NDUFC1 knockdown also inhibited SGC-7901 cell growth in vivo and suppressed Ki67 expression in xenograft tumors. More importantly, we found that NDUFC1 downregulation made the levels of P-Akt, P-mTOR, CCND1, CDK6, PIK3CA, Bcl-2, Survivin, and XIAP decreased, and that PI3K/AKT signaling pathway agonist SC79 rescued the inhibitory effects on cell proliferation and migration, reversed the promoted effects on cell apoptosis caused by NDUFC1 knockdown. More importantly, compared with NDUFC1 knockdown group, the expression of P-Akt, Bcl-2, Survivin, and XIAP was raised in shNDUFC1 + SC79 group. Thus, our suspicion was that NDUFC1 exacerbates NSCLC progression via PI3K/Akt pathway. Taken together, our study indicated that targeting NDUFC1 could open innovative perspectives for new multi-targeting approaches in the treatment of gastric cancer.
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Affiliation(s)
- Liang Xu
- Department of Organ Transplantation, The Second Affiliated Hospital of Hainan Medical University, Hainan, China
| | - Xiuxiu Chen
- Surgery of Breast Nail, The Second Affiliated Hospital of Hainan Medical University, Hainan, China
| | - Hongtao Jiang
- Department of Organ Transplantation, The Second Affiliated Hospital of Hainan Medical University, Hainan, China
| | - Jian Xu
- Department of Organ Transplantation, The Second Affiliated Hospital of Hainan Medical University, Hainan, China
| | - Lixia Wang
- Department of Organ Transplantation, The Second Affiliated Hospital of Hainan Medical University, Hainan, China
| | - Yuemin Sun
- Department of Pancreatic & Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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7
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Wang Y, Wang Y, Liu L, Cui H. Ovariectomy induces abdominal fat accumulation by improving gonadotropin-releasing hormone secretion in mouse. Biochem Biophys Res Commun 2021; 588:111-117. [PMID: 34953207 DOI: 10.1016/j.bbrc.2021.12.039] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2021] [Revised: 12/08/2021] [Accepted: 12/13/2021] [Indexed: 11/02/2022]
Abstract
The ovariectomy would induce the occurrence of obesity, but its regulatory mechanism is not clear. This study aimed to elucidate the regulation on fat accumulation for ovariectomy in mouse. In the current study, the abdominal fat mass dramatically increased in OVX mice compared with sham mice at eighth week after ovariectomy, accompanied with the higher GnRH level in blood and abdominal fat tissue. Also, a decrease of the abdominal fat mass was occurred in OVX mice with a GnRH-antagonist injection. Furthermore, the results in vivo and in vitro confirmed that GnRH promoted the transition of G1/S phase by upregulating CCND1 and CCNE1 mRNA levels by the mediation of GnRHR via the PKA-CREB pathway. Meanwhile, the higher FSH secretion was induced by increase GnRH and accelerate fat deposition in abdominal fat tissue. Our findings are the first to elucidate the effect mechanism of ovariectomy on obesity in mouse. GnRH stimulates fat accumulation in adipocytes via PKA-CREB pathway by directly promoting cell proliferation for driving the cell cycle and simultaneously accelerating differentiation for improving the FSH secretion.
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Affiliation(s)
- Yongli Wang
- State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100193, China.
| | - Yidong Wang
- State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100193, China.
| | - Li Liu
- State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100193, China.
| | - Huanxian Cui
- State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100193, China.
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8
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Gallo A, Ronzio M, Bezzecchi E, Mantovani R, Dolfini D. NF-Y subunits overexpression in gastric adenocarcinomas (STAD). Sci Rep 2021; 11:23764. [PMID: 34887475 PMCID: PMC8660849 DOI: 10.1038/s41598-021-03027-y] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2021] [Accepted: 11/22/2021] [Indexed: 12/12/2022] Open
Abstract
NF-Y is a pioneer transcription factor-TF-formed by the Histone-like NF-YB/NF-YC subunits and the regulatory NF-YA. It binds to the CCAAT box, an element enriched in promoters of genes overexpressed in many types of cancer. NF-YA is present in two major isoforms-NF-YAs and NF-YAl-due to alternative splicing, overexpressed in epithelial tumors. Here we analyzed NF-Y expression in stomach adenocarcinomas (STAD). We completed the partitioning of all TCGA tumor samples (450) according to molecular subtypes proposed by TCGA and ACRG, using the deep learning tool DeepCC. We analyzed differentially expressed genes-DEG-for enriched pathways and TFs binding sites in promoters. CCAAT is the predominant element only in the core group of genes upregulated in all subtypes, with cell-cycle gene signatures. NF-Y subunits are overexpressed, particularly NF-YA. NF-YAs is predominant in CIN, MSI and EBV TCGA subtypes, NF-YAl is higher in GS and in the ACRG EMT subtypes. Moreover, NF-YAlhigh tumors correlate with a discrete Claudinlow cohort. Elevated NF-YB levels are protective in MSS;TP53+ patients, whereas high NF-YAl/NF-YAs ratios correlate with worse prognosis. We conclude that NF-Y isoforms are associated to clinically relevant features of gastric cancer.
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Affiliation(s)
- Alberto Gallo
- Dipartimento di Bioscienze, Università degli Studi di Milano, Via Celoria 26, 20133, Milan, Italy
| | - Mirko Ronzio
- Dipartimento di Bioscienze, Università degli Studi di Milano, Via Celoria 26, 20133, Milan, Italy
| | - Eugenia Bezzecchi
- Dipartimento di Bioscienze, Università degli Studi di Milano, Via Celoria 26, 20133, Milan, Italy
| | - Roberto Mantovani
- Dipartimento di Bioscienze, Università degli Studi di Milano, Via Celoria 26, 20133, Milan, Italy
| | - Diletta Dolfini
- Dipartimento di Bioscienze, Università degli Studi di Milano, Via Celoria 26, 20133, Milan, Italy.
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9
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Thummadi NB, T M, Vindal V, P M. Prioritizing the candidate genes related to cervical cancer using the moment of inertia tensor. Proteins 2021; 90:363-371. [PMID: 34468998 DOI: 10.1002/prot.26226] [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: 06/14/2021] [Revised: 08/07/2021] [Accepted: 08/16/2021] [Indexed: 12/24/2022]
Abstract
It is well known that cervical cancer poses the fourth most malignancy threat to women worldwide among all cancer types. There is a tremendous improvement in realizing the underlying molecular associations in cervical cancer. Several studies reported pieces of evidence for the involvement of various genes in the disease progression. However, with the ever-evolving bioinformatics tools, there has been an upsurge in predicting numerous genes responsible for cervical cancer progression and making it highly complex to target the genes for further evaluation. In this article, we prioritized the candidate genes based on the sequence similarity analysis with known cancer genes. For this purpose, we used the concept of the moment of inertia tensor, which reveals the similarities between the protein sequences more efficiently. Tensor for moment of inertia explores the similarity of the protein sequences based on the physicochemical properties of amino acids. From our analysis, we obtained 14 candidate cervical cancer genes, which are highly similar to known cervical cancer genes. Further, we analyzed the GO terms and prioritized these genes based on the number of hits with biological process, molecular functions, and their involvement in KEGG pathways. We also discussed the evidence-based involvement of the prioritized genes in other cancers and listed the available drugs for those genes.
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Affiliation(s)
- Neelesh Babu Thummadi
- Department of Animal Biology, School of Life Sciences, University of Hyderabad, Gachibowli, Hyderabad, India
| | - Mallikarjuna T
- Department of Biotechnology and Bioinformatics, School of Life Sciences, University of Hyderabad, Gachibowli, Hyderabad, India
| | - Vaibhav Vindal
- Department of Biotechnology and Bioinformatics, School of Life Sciences, University of Hyderabad, Gachibowli, Hyderabad, India
| | - Manimaran P
- School of Physics, University of Hyderabad, Gachibowli, Hyderabad, India
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10
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Huang H, Wang Z, Li Y, Zhao Q, Niu Z. Amplification of the human epidermal growth factor receptor 2 ( HER2) gene is associated with a microsatellite stable status in Chinese gastric cancer patients. J Gastrointest Oncol 2021; 12:377-387. [PMID: 34012633 PMCID: PMC8107625 DOI: 10.21037/jgo-21-47] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2020] [Accepted: 04/04/2021] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Gastric cancer (GC) is one of the most common cancers worldwide. However, little is known about the combination of HER2 amplification and microsatellite instability (MSI) status in GC. This study aimed to analyze the correlation of HER2 amplification with microsatellite instability (MSI) status, clinical characteristics, and the tumor mutational burden (TMB) of patients. METHODS A total of 192 gastric cancer (GC) patients were enrolled in this cohort. To analyze genomic alterations (GAs), deep sequencing was performed on 450 target cancer genes. TMB was measured by an in-house algorithm. MSI status was inferred based on the MANTIS (Microsatellite Analysis for Normal-Tumor InStability) score. RESULTS The most frequently amplified genes in the GC patients included cyclin E1 (CCNE1), human epidermal growth factor receptor 2 (HER2), fibroblast growth factor receptor 2 (FGFR2), cyclin D1 (CCND1), fibroblast growth factor 19 (FGF19), fibroblast growth factor 3 (FGF3), and fibroblast growth factor 4 (FGF4). The frequency of HER2 amplification was 9.38% (18/192). HER2 amplification was higher in females than in males (14.52% vs. 6.92%, respectively, P=0.091), however, MSI was higher in males compared to females (7.69% vs. 4.84%, respectively, P=0.46). HER2 amplification was higher in metastatic loci compared to primary lesions (23.08% vs. 8.38%, respectively, P=0.079) and was lower in patients with high TMB (TMB-H) compared to those with low TMB (TMB-L) (4.0% vs. 11.35%, respectively, P=0.12). While the frequency of MSI in metastatic foci was higher than that in primary lesions (15.38% vs. 6.15%, respectively, P=0.48), MSI status was highly associated with TMB-H (20% vs. 0%, respectively, P=3.66×10-7). Furthermore, HER2 amplification was negatively correlated with MSI status in Chinese GC patients. CONCLUSIONS HER2 amplification was negatively correlated with TMB-H and MSI status, and MSI status was significantly associated with TMB-H in Chinese GC patients. These data suggested that HER2 amplification might be a negative indicator for GC immunotherapy.
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Affiliation(s)
- He Huang
- Department of Gastrointestinal Surgery, The First Hospital of Shanxi Medical University, Shanxi, China
| | - Zhengkun Wang
- Department of Gastrointestinal Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Yi Li
- Department of Gastrointestinal Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Qun Zhao
- Department of Gastrosurgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Zhaojian Niu
- Department of Gastrointestinal Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China
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11
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Molinari C, Tedaldi G, Rebuzzi F, Morgagni P, Capelli L, Ravaioli S, Tumedei MM, Scarpi E, Tomezzoli A, Bernasconi R, Ambrosio MR, D'Ignazio A, Solaini L, Limarzi F, Ercolani G, Martinelli G, Ulivi P, Saragoni L. Early Gastric Cancer: identification of molecular markers able to distinguish submucosa-penetrating lesions with different prognosis. Gastric Cancer 2021; 24:392-401. [PMID: 33156452 DOI: 10.1007/s10120-020-01135-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2020] [Accepted: 10/18/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND Early Gastric Cancer (EGC) reaches 25% of the gastric cancers surgically treated in some areas of Northeastern Italy and is usually characterized by a good prognosis. However, among EGCs classified according to Kodama's criteria, Pen A subgroup is characterized by extensive submucosal invasion, lymph node metastases and worse prognosis, whereas Pen B subgroup by better prognosis. The aim of the study was to characterize the differences between Pen A, Pen B and locally advanced gastric cancer (T3N0) in order to identify biomarkers involved in aggressiveness and clinical outcome. METHODS We selected 33 Pen A, 34 Pen B and 20 T3N0 tumors and performed immunohistochemistry of mucins, copy number variation analysis of a gene panel, microsatellite instability (MSI), TP53 mutation and loss of heterozygosity (LOH) analyses. RESULTS Pen A subgroup was characterized by MUC6 overexpression (p = 0.021). Otherwise, the Pen B subgroup was significantly associated with the amplification of GATA6 gene (p = 0.002). The higher percentage of MSI tumors was observed in T3N0 group (p = 0.002), but no significant differences between EGC types were found. Finally, TP53 gene analysis showed that 32.8% of Pen tumors have a mutation in exons 5-8 and 50.0% presented LOH. Co-occurrence of TP53 mutation and LOH mainly characterized Pen A tumors (p = 0.022). CONCLUSIONS Our analyses revealed that clinico-pathological parameters, microsatellite status and frequency of TP53 mutations do not seem to distinguish Pen subgroups. Conversely, the amplification of GATA6 was associated with Pen B, as well as the overexpression of MUC6 and the TP53mut/LOH significantly characterized Pen A.
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Affiliation(s)
- Chiara Molinari
- Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, via P. Maroncelli 40, 47014, Meldola, FC, Italy
| | - Gianluca Tedaldi
- Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, via P. Maroncelli 40, 47014, Meldola, FC, Italy.
| | - Francesca Rebuzzi
- Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, via P. Maroncelli 40, 47014, Meldola, FC, Italy
| | - Paolo Morgagni
- Department of Surgery, Morgagni-Pierantoni Hospital, Forlì, Italy
| | - Laura Capelli
- Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, via P. Maroncelli 40, 47014, Meldola, FC, Italy
| | - Sara Ravaioli
- Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, via P. Maroncelli 40, 47014, Meldola, FC, Italy
| | - Maria Maddalena Tumedei
- Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, via P. Maroncelli 40, 47014, Meldola, FC, Italy
| | - Emanuela Scarpi
- Biostatistics and Clinical Trials Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy
| | - Anna Tomezzoli
- Department of Pathology, University of Verona, Verona, Italy
| | | | - Maria Raffaella Ambrosio
- Pathology Unit, University of Siena, Siena, Italy
- Pathology Unit, Azienda USL Toscana Nord-Ovest, Pisa, Italy
| | | | - Leonardo Solaini
- Department of Surgery, Morgagni-Pierantoni Hospital, Forlì, Italy
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Francesco Limarzi
- Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, via P. Maroncelli 40, 47014, Meldola, FC, Italy
| | - Giorgio Ercolani
- Department of Surgery, Morgagni-Pierantoni Hospital, Forlì, Italy
| | - Giovanni Martinelli
- Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy
| | - Paola Ulivi
- Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, via P. Maroncelli 40, 47014, Meldola, FC, Italy
| | - Luca Saragoni
- Pathology Unit, Morgagni-Pierantoni Hospital, Forlì, Italy
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12
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Li L, Dong Z, Shi P, Tan L, Xu J, Huang P, Wang Z, Cui H, Yang L. Bruceine D inhibits Cell Proliferation Through Downregulating LINC01667/MicroRNA-138-5p/Cyclin E1 Axis in Gastric Cancer. Front Pharmacol 2021; 11:584960. [PMID: 33390953 PMCID: PMC7774499 DOI: 10.3389/fphar.2020.584960] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2020] [Accepted: 10/13/2020] [Indexed: 12/24/2022] Open
Abstract
Objective: Gastric cancer is one of the most common malignant tumors. Bruceine D (BD) is one of the extracts of Brucea javanica. In recent years, it has been reported that BD has anti-tumor activity in some human cancers through different mechanisms. Here, this study try to explore the effect of BD on gastric cancer and its regulatory mechanism. Methods: Cell proliferation ability was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assays, 5-bromo-2-deoxyuridine (BrdU) staining and soft agar colony formation assay, respectively. The tumor xenograft model was used to verify the effect of BD on the tumorigenicity of gastric cancer cells in vivo. Flow cytometry analysis and Western blot assay were performed to detect cell cycle and apoptosis. Gastric cancer cells were analyzed by transcriptome sequencing. The interaction between LINC01667, microRNA-138-5p (miR-138-5p) and Cyclin E1 was verified by dual luciferase experiment and RT-PCR assays. Results: We found that BD significantly inhibited cell proliferation and induced cell cycle arrest at S phase in gastric cancer cells. Transcriptome analysis found that the expression of a long non-coding RNA, LINC01667, were significantly down-regulated after BD treatment. Mechanically, it was discovered that LINC01667 upregulated the expression of Cyclin E1 by sponging miR-138-5p. Furthermore, BD enhanced the chemosensitivity of gastric cancer cells to doxorubicin, a clinically used anti-cancer agent. Conclusion: BD inhibit the growth of gastric cancer cells by downregulating the LINC01667/miR-138-5p/Cyclin E1 axis. In addition, BD enhances the chemosensitivity of gastric cancer cells to doxorubicin. This study indicates that BD may be used as a candidate drug for the treatment of patients with gastric cancer.
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Affiliation(s)
- Lin Li
- State Key Laboratory of Silkworm Genome Biology, Institute of Sericulture and Systems Biology, College of Sericulture and Textile and Biomass Science, Southwest University, Chongqing, China.,Department of Immunology, School of Basic Medicine, Southwest Medical University, Luzhou, China.,Cancer Center, Reproductive Medicine Center, Medical Research Institute, Southwest University, Chongqing, China.,Engineering Research Center for Cancer Biomedical and Translational Medicine, Southwest University, Chongqing, China.,Chongqing Engineering and Technology Research Center for Silk Biomaterials and Regenerative Medicine, Southwest University, Chongqing, China
| | - Zhen Dong
- State Key Laboratory of Silkworm Genome Biology, Institute of Sericulture and Systems Biology, College of Sericulture and Textile and Biomass Science, Southwest University, Chongqing, China.,Cancer Center, Reproductive Medicine Center, Medical Research Institute, Southwest University, Chongqing, China.,Engineering Research Center for Cancer Biomedical and Translational Medicine, Southwest University, Chongqing, China.,Chongqing Engineering and Technology Research Center for Silk Biomaterials and Regenerative Medicine, Southwest University, Chongqing, China.,NHC Key Laboratory of Birth Defects and Reproductive Health (Chongqing Key Laboratory of Birth Defects and Reproductive Health, Chongqing Population and Family Planning Science and Technology Research Institute), Chongqing, China
| | - Pengfei Shi
- State Key Laboratory of Silkworm Genome Biology, Institute of Sericulture and Systems Biology, College of Sericulture and Textile and Biomass Science, Southwest University, Chongqing, China.,Cancer Center, Reproductive Medicine Center, Medical Research Institute, Southwest University, Chongqing, China.,Engineering Research Center for Cancer Biomedical and Translational Medicine, Southwest University, Chongqing, China.,Chongqing Engineering and Technology Research Center for Silk Biomaterials and Regenerative Medicine, Southwest University, Chongqing, China
| | - Li Tan
- State Key Laboratory of Silkworm Genome Biology, Institute of Sericulture and Systems Biology, College of Sericulture and Textile and Biomass Science, Southwest University, Chongqing, China.,Cancer Center, Reproductive Medicine Center, Medical Research Institute, Southwest University, Chongqing, China.,Engineering Research Center for Cancer Biomedical and Translational Medicine, Southwest University, Chongqing, China.,Chongqing Engineering and Technology Research Center for Silk Biomaterials and Regenerative Medicine, Southwest University, Chongqing, China
| | - Jie Xu
- State Key Laboratory of Silkworm Genome Biology, Institute of Sericulture and Systems Biology, College of Sericulture and Textile and Biomass Science, Southwest University, Chongqing, China.,Cancer Center, Reproductive Medicine Center, Medical Research Institute, Southwest University, Chongqing, China.,Engineering Research Center for Cancer Biomedical and Translational Medicine, Southwest University, Chongqing, China.,Chongqing Engineering and Technology Research Center for Silk Biomaterials and Regenerative Medicine, Southwest University, Chongqing, China
| | - Pan Huang
- State Key Laboratory of Silkworm Genome Biology, Institute of Sericulture and Systems Biology, College of Sericulture and Textile and Biomass Science, Southwest University, Chongqing, China.,Cancer Center, Reproductive Medicine Center, Medical Research Institute, Southwest University, Chongqing, China.,Engineering Research Center for Cancer Biomedical and Translational Medicine, Southwest University, Chongqing, China.,Chongqing Engineering and Technology Research Center for Silk Biomaterials and Regenerative Medicine, Southwest University, Chongqing, China
| | - Zhongze Wang
- State Key Laboratory of Silkworm Genome Biology, Institute of Sericulture and Systems Biology, College of Sericulture and Textile and Biomass Science, Southwest University, Chongqing, China.,Cancer Center, Reproductive Medicine Center, Medical Research Institute, Southwest University, Chongqing, China.,Engineering Research Center for Cancer Biomedical and Translational Medicine, Southwest University, Chongqing, China.,Chongqing Engineering and Technology Research Center for Silk Biomaterials and Regenerative Medicine, Southwest University, Chongqing, China
| | - Hongjuan Cui
- State Key Laboratory of Silkworm Genome Biology, Institute of Sericulture and Systems Biology, College of Sericulture and Textile and Biomass Science, Southwest University, Chongqing, China.,Cancer Center, Reproductive Medicine Center, Medical Research Institute, Southwest University, Chongqing, China.,Engineering Research Center for Cancer Biomedical and Translational Medicine, Southwest University, Chongqing, China.,Chongqing Engineering and Technology Research Center for Silk Biomaterials and Regenerative Medicine, Southwest University, Chongqing, China.,NHC Key Laboratory of Birth Defects and Reproductive Health (Chongqing Key Laboratory of Birth Defects and Reproductive Health, Chongqing Population and Family Planning Science and Technology Research Institute), Chongqing, China
| | - Liqun Yang
- State Key Laboratory of Silkworm Genome Biology, Institute of Sericulture and Systems Biology, College of Sericulture and Textile and Biomass Science, Southwest University, Chongqing, China.,Cancer Center, Reproductive Medicine Center, Medical Research Institute, Southwest University, Chongqing, China.,Engineering Research Center for Cancer Biomedical and Translational Medicine, Southwest University, Chongqing, China.,Chongqing Engineering and Technology Research Center for Silk Biomaterials and Regenerative Medicine, Southwest University, Chongqing, China
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13
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Wang H, Ren S, Xu Y, Miao W, Huang X, Qu Z, Li J, Liu X, Kong P. MicroRNA-195 reverses the resistance to temozolomide through targeting cyclin E1 in glioma cells. Anticancer Drugs 2020; 30:81-88. [PMID: 30273182 PMCID: PMC6287895 DOI: 10.1097/cad.0000000000000700] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Glioma is the most common malignant tumor of the central nervous system with poor survival. Temozolomide (TMZ) is the first-line chemotherapy drug for initial and recurrent glioma treatment with a relatively good efficacy, which exerts its antitumor effects mainly through cell death induced by DNA double-strand breaks in the G1 and S phases. However, endogenous or acquired resistance to TMZ limits glioma patients’ clinical outcome and is also an important cause of glioma replase. MicroRNA-195 (miR-195) plays an important role in the regulation of G1-phase/S-phase transition, DNA damage repair, and apoptosis of tumor cells. We found that miR-195 expression was significantly decreased in TMZ-resistant glioma cells induced with TMZ and correlated to the resistance index negatively. Also, the exogenous expression of miR-195 reversed TMZ resistance and induced the apoptosis of TMZ-resistant glioblastoma cells. Further bioinformatics analysis showed cyclin E1 (CCNE1) was a potential target gene of miR-195. Knockdown of CCNE1 partially reversed the effect of decreased miR-195 on TMZ resistance. The data from The Cancer Genome Atlas – Cancer Genome further suggested that hsa-miR-195 could negatively regulate the expression of CCNE1 in glioma. In conclusion, miR-195 reverses the resistance to TMZ by targeting CCNE1 in glioma cells and it could act as a potential target for treatment in glioma with TMZ resistance.
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Affiliation(s)
| | - Shuxian Ren
- Department of Neurosurgery, The First Hospital.,Department of Neurosurgery, Tianjin Third Centeral Hospital, Tianjin
| | - Yongming Xu
- Department of Neurosurgery, The First Hospital.,Department of Neurosurgery, QuZhou People's Hospital, QuZhou, Zhejiang, People's Republic of China
| | - Wang Miao
- Department of Neurosurgery, The First Hospital
| | | | - Zhizhao Qu
- Department of Neurosurgery, The First Hospital
| | - Jinhu Li
- Department of Neurosurgery, The First Hospital
| | | | - Pengzhou Kong
- Shanxi Key Laboratory of Carcinogenesis and Translational Research of Esophageal Cancer.,Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University
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14
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Shi R, Bao X, Rogowski P, Schäfer C, Schmidt-Hegemann NS, Unger K, Lu S, Sun J, Buchner A, Stief C, Belka C, Li M. Establishment and Validation of an Individualized Cell Cycle Process-Related Gene Signature to Predict Cancer-Specific Survival in Patients with Bladder Cancer. Cancers (Basel) 2020; 12:cancers12051146. [PMID: 32370292 PMCID: PMC7281226 DOI: 10.3390/cancers12051146] [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: 04/07/2020] [Revised: 04/24/2020] [Accepted: 04/24/2020] [Indexed: 12/20/2022] Open
Abstract
More accurate models are essential to identify high-risk bladder cancer (BCa) patients who will benefit from adjuvant therapies and thus helpful to facilitate personalized management of BCa. Among various cancer-related hallmarks and pathways, cell cycle process (CCP) was identified as a dominant risk factor for cancer-specific survival (CSS) in BCa. Using a series of bioinformatic and statistical approaches, a CCP-related gene signature was established, and the prognostic value was validated in other independent BCa cohorts. In addition, the risk score derived from the gene signature serves as a promising marker for therapeutic resistance. In combination with clinicopathological features, a nomogram was constructed to provide more accurate prediction for CSS, and a decision tree was built to identify high-risk subgroup of muscle invasive BCa patients. Overall, the gene signature could be a useful tool to predict CSS and help to identify high-risk subgroup of BCa patients, which may benefit from intensified adjuvant therapy.
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Affiliation(s)
- Run Shi
- Department of Radiation Oncology, University Hospital, LMU Munich, D-81377 Munich, Germany; (R.S.); (P.R.); (C.S.); (N.-S.S.-H.); (K.U.); (J.S.); (C.B.)
| | - Xuanwen Bao
- Technical University of Munich, D-80333 Munich, Germany;
| | - Paul Rogowski
- Department of Radiation Oncology, University Hospital, LMU Munich, D-81377 Munich, Germany; (R.S.); (P.R.); (C.S.); (N.-S.S.-H.); (K.U.); (J.S.); (C.B.)
| | - Christian Schäfer
- Department of Radiation Oncology, University Hospital, LMU Munich, D-81377 Munich, Germany; (R.S.); (P.R.); (C.S.); (N.-S.S.-H.); (K.U.); (J.S.); (C.B.)
| | - Nina-Sophie Schmidt-Hegemann
- Department of Radiation Oncology, University Hospital, LMU Munich, D-81377 Munich, Germany; (R.S.); (P.R.); (C.S.); (N.-S.S.-H.); (K.U.); (J.S.); (C.B.)
| | - Kristian Unger
- Department of Radiation Oncology, University Hospital, LMU Munich, D-81377 Munich, Germany; (R.S.); (P.R.); (C.S.); (N.-S.S.-H.); (K.U.); (J.S.); (C.B.)
- Research Unit Radiation Cytogenetics, Helmholtz Center Munich, German Research Center for Environmental Health GmbH, D-85764 Neuherberg, Germany
| | - Shun Lu
- Department of Radiotherapy, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610041, China;
| | - Jing Sun
- Department of Radiation Oncology, University Hospital, LMU Munich, D-81377 Munich, Germany; (R.S.); (P.R.); (C.S.); (N.-S.S.-H.); (K.U.); (J.S.); (C.B.)
| | - Alexander Buchner
- Department of Urology, University Hospital, LMU Munich, D-81377 Munich, Germany; (A.B.); (C.S.)
| | - Christian Stief
- Department of Urology, University Hospital, LMU Munich, D-81377 Munich, Germany; (A.B.); (C.S.)
| | - Claus Belka
- Department of Radiation Oncology, University Hospital, LMU Munich, D-81377 Munich, Germany; (R.S.); (P.R.); (C.S.); (N.-S.S.-H.); (K.U.); (J.S.); (C.B.)
| | - Minglun Li
- Department of Radiation Oncology, University Hospital, LMU Munich, D-81377 Munich, Germany; (R.S.); (P.R.); (C.S.); (N.-S.S.-H.); (K.U.); (J.S.); (C.B.)
- Correspondence:
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15
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Zhou H, Liu Q, Shi X, Liu Y, Cao D, Yang J. Distinct gene expression profiles associated with clinical outcomes in patients with ovarian clear cell carcinoma and high-grade serous ovarian carcinoma. J Ovarian Res 2020; 13:38. [PMID: 32295618 PMCID: PMC7161165 DOI: 10.1186/s13048-020-00641-8] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2019] [Accepted: 03/31/2020] [Indexed: 12/28/2022] Open
Abstract
Background Ovarian clear cell carcinoma (OCCC) is the second most common ovarian cancer after serous carcinoma in Southeast Asia. OCCC has a more unfavourable clinical outcome due to a poor response to platinum-based chemotherapy compared with serous carcinoma. The identification of biomarkers related to the prognosis of OCCC is critically important for an improved understanding of the biology that drives OCCC progression and leads to poor outcomes. To detect differences in gene expression profiles between OCCC and high-grade serous ovarian carcinoma (HGSOC), twelve patients with OCCC and twelve patients with HGSOC were recruited in whom the pathological diagnosis was confirmed on surgically resected specimens. Results Compared with HGSOC, OCCC has 609 differentially expression genes, and 199 are significantly different (P < 0.05). These genes are involved in the cell cycle, apoptosis, DNA damage repair, the PI3K pathway and so on. There were 164 differentially expressed genes in the PI3K pathway. There were 35 overexpressed genes in OCCC, while there were 12 overexpressed genes in HGSOC. Among these differentially expressed genes, we found that the MET gene and the CCNE1 gene were overexpressed in OCCC and associated with a worse prognosis. Conclusions In conclusion, there are many differentially expressed genes in OCCC and HGSOC, which indicates that the two kinds of tumours differ greatly in tumourigenesis and provides a theoretical basis for targeted therapy in the future. Further studies need to be performed to clarify the association of the differentially expressed genes with the unfavourable prognosis in OCCC.
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Affiliation(s)
- Huimei Zhou
- Department of Gynaecologic Oncology, Peking Union Medical College Hospital, 1 Shuaifuyuan, Dongcheng-qu, Beijing, People's Republic of China
| | - Qian Liu
- Department of Gynaecologic Oncology, Peking Union Medical College Hospital, 1 Shuaifuyuan, Dongcheng-qu, Beijing, People's Republic of China
| | - Xiaohua Shi
- Department of Pathology, Peking Union Medical College Hospital, Beijing, People's Republic of China
| | - Yue Liu
- Department of Gynaecologic Oncology, Peking Union Medical College Hospital, 1 Shuaifuyuan, Dongcheng-qu, Beijing, People's Republic of China
| | - Dongyan Cao
- Department of Gynaecologic Oncology, Peking Union Medical College Hospital, 1 Shuaifuyuan, Dongcheng-qu, Beijing, People's Republic of China
| | - Jiaxin Yang
- Department of Gynaecologic Oncology, Peking Union Medical College Hospital, 1 Shuaifuyuan, Dongcheng-qu, Beijing, People's Republic of China.
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16
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Matsuoka T, Yashiro M. Precision medicine for gastrointestinal cancer: Recent progress and future perspective. World J Gastrointest Oncol 2020; 12:1-20. [PMID: 31966910 PMCID: PMC6960076 DOI: 10.4251/wjgo.v12.i1.1] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2019] [Revised: 10/12/2019] [Accepted: 11/04/2019] [Indexed: 02/05/2023] Open
Abstract
Gastrointestinal (GI) cancer has a high tumor incidence and mortality rate worldwide. Despite significant improvements in radiotherapy, chemotherapy, and targeted therapy for GI cancer over the last decade, GI cancer is characterized by high recurrence rates and a dismal prognosis. There is an urgent need for new diagnostic and therapeutic approaches. Recent technological advances and the accumulation of clinical data are moving toward the use of precision medicine in GI cancer. Here we review the application and status of precision medicine in GI cancer. Analyses of liquid biopsy specimens provide comprehensive real-time data of the tumor-associated changes in an individual GI cancer patient with malignancy. With the introduction of gene panels including next-generation sequencing, it has become possible to identify a variety of mutations and genetic biomarkers in GI cancer. Although the genomic aberration of GI cancer is apparently less actionable compared to other solid tumors, novel informative analyses derived from comprehensive gene profiling may lead to the discovery of precise molecular targeted drugs. These progressions will make it feasible to incorporate clinical, genome-based, and phenotype-based diagnostic and therapeutic approaches and apply them to individual GI cancer patients for precision medicine.
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Affiliation(s)
- Tasuku Matsuoka
- Department of Gastroenterological Surgery, Osaka City University Graduate School of Medicine, Osaka 5458585, Japan
| | - Masakazu Yashiro
- Department of Gastroenterological Surgery, Osaka City University Graduate School of Medicine, Osaka 5458585, Japan
- Oncology Institute of Geriatrics and Medical Science, Osaka City University Graduate School of Medicine, Osaka 5458585, Japan
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17
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Guo Y, Wang Y, Ma Y, Chen G, Yue P, Li Y. Upregulation of lncRNA SUMO1P3 promotes proliferation, invasion and drug resistance in gastric cancer through interacting with the CNBP protein. RSC Adv 2020; 10:6006-6016. [PMID: 35497433 PMCID: PMC9049591 DOI: 10.1039/c9ra09497k] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2019] [Accepted: 01/19/2020] [Indexed: 02/02/2023] Open
Abstract
Gastric cancer (GC) is one type of the most common malignancies in the world. In the process of exploring the pathological mechanism of GC and searching for treatment methods, long non-coding RNAs (lncRNAs) display significant participation. Small ubiquitin-like modifier 1 pseudogene 3 (SUMO1P3) is a newly identified lncRNA, of which the biological role and underlying mechanism in GC progression have not been elucidated. Here, through the comparisons between GC patients' tumor and normal tissue samples, as well as normal gastric mucosal and GC cell lines, we confirmed a significant upregulation of SUMO1P3 in GC tissues and cell lines. Meanwhile, significant upregulation of SUMO1P3 was observed in advanced GC patients, and patients with high level of SUMO1P3 displayed a poor survival rate. Next, gain- and loss-of-function experiments were performed in GC cells, and the results exhibited that SUMO1P3 positively regulated proliferation and invasion of GC cells. Then, we constructed drug-resistant GC cell strains and explore the role of SUMO1P3 in the resistance of GC cells to cisplatin (DDP) and 5-fluorouracil (5-Fu). Finally, bioinformatics analysis and RNA pull-down assay demonstrated that SUMO1P3 could directly interact with cellular nucleic acid binding protein (CNBP), thus positively regulating CNBP downstream oncogenes c-myc and cyclin D1 (CCND1). Our findings indicate that SUMO1P3 promotes proliferation, invasion and drug resistance of GC cells by interacting with CNBP, which reveals a potential prognostic biomarker and a novel therapeutic target for GC. Gastric cancer (GC) is one type of the most common malignancies in the world.![]()
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Affiliation(s)
- Yinmou Guo
- The First Ward
- Department of Oncology
- The First People's Hospital of Shangqiu City
- Shangqiu 476100
- China
| | - Yumei Wang
- Department of Pediatrics
- The First People's Hospital of Shangqiu City
- Shangqiu 476100
- China
| | - Yali Ma
- The First Ward
- Department of Oncology
- The First People's Hospital of Shangqiu City
- Shangqiu 476100
- China
| | - Gongbin Chen
- The First Ward
- Department of Oncology
- The First People's Hospital of Shangqiu City
- Shangqiu 476100
- China
| | - Peiru Yue
- The First Ward
- Department of Oncology
- The First People's Hospital of Shangqiu City
- Shangqiu 476100
- China
| | - Yang Li
- The First Ward
- Department of Oncology
- The First People's Hospital of Shangqiu City
- Shangqiu 476100
- China
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18
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Hewitt LC, Saito Y, Wang T, Matsuda Y, Oosting J, Silva ANS, Slaney HL, Melotte V, Hutchins G, Tan P, Yoshikawa T, Arai T, Grabsch HI. KRAS status is related to histological phenotype in gastric cancer: results from a large multicentre study. Gastric Cancer 2019; 22:1193-1203. [PMID: 31111275 PMCID: PMC6811379 DOI: 10.1007/s10120-019-00972-6] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2019] [Accepted: 05/06/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND Gastric cancer (GC) is histologically a very heterogeneous disease, and the temporal development of different histological phenotypes remains unclear. Recent studies in lung and ovarian cancer suggest that KRAS activation (KRASact) can influence histological phenotype. KRASact likely results from KRAS mutation (KRASmut) or KRAS amplification (KRASamp). The aim of the study was to investigate whether KRASmut and/or KRASamp are related to the histological phenotype in GC. METHODS Digitized haematoxylin/eosin-stained slides from 1282 GC resection specimens were classified according to Japanese Gastric Cancer Association (JGCA) and the Lauren classification by at least two observers. The relationship between KRAS status, predominant histological phenotype and clinicopathological variables was assessed. RESULTS KRASmut and KRASamp were found in 68 (5%) and 47 (7%) GCs, respectively. Within the KRASmut and KRASamp cases, the most frequent GC histological phenotype was moderately differentiated tubular 2 (tub2) type (KRASmut: n = 27, 40%; KRASamp: n = 21, 46%) or intestinal type (KRASmut: n = 41, 61%; KRASamp: n = 23, 50%). Comparing individual histological subtypes, mucinous carcinoma displayed the highest frequency of KRASmut (JGCA: n = 6, 12%, p = 0.012; Lauren: n = 6, 12%, p = 0.013), and KRASamp was more frequently found in poorly differentiated solid type (n = 12, 10%, p = 0.267) or indeterminate type (n = 12, 10%, p = 0.480) GC. 724 GCs (57%) had intratumour morphological heterogeneity. CONCLUSIONS This is the largest GC study investigating KRAS status and histological phenotype. We identified a relationship between KRASmut and mucinous phenotype. The high level of intratumour morphological heterogeneity could reflect KRASmut heterogeneity, which may explain the failure of anti-EGFR therapy in GC.
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Affiliation(s)
- Lindsay C. Hewitt
- Department of Pathology, GROW School for Oncology and Developmental Biology, Maastricht University Medical Center+, P. Debyelaan 25, 6229 HX Maastricht, The Netherlands ,Division of Pathology and Data Analytics, Leeds Institute of Medical Research at St. James’s, University of Leeds, Leeds, UK
| | - Yuichi Saito
- Department of Pathology, GROW School for Oncology and Developmental Biology, Maastricht University Medical Center+, P. Debyelaan 25, 6229 HX Maastricht, The Netherlands
| | - Tan Wang
- Department of Pathology, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, Tokyo, Japan ,Department of Comprehensive Pathology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Yoko Matsuda
- Department of Pathology, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, Tokyo, Japan
| | - Jan Oosting
- Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands
| | - Arnaldo N. S. Silva
- Division of Pathology and Data Analytics, Leeds Institute of Medical Research at St. James’s, University of Leeds, Leeds, UK
| | - Hayley L. Slaney
- Division of Pathology and Data Analytics, Leeds Institute of Medical Research at St. James’s, University of Leeds, Leeds, UK
| | - Veerle Melotte
- Department of Pathology, GROW School for Oncology and Developmental Biology, Maastricht University Medical Center+, P. Debyelaan 25, 6229 HX Maastricht, The Netherlands ,Department of Clinical Genetics, Erasmus University Medical Center, University of Rotterdam, Rotterdam, The Netherlands
| | - Gordon Hutchins
- Division of Pathology and Data Analytics, Leeds Institute of Medical Research at St. James’s, University of Leeds, Leeds, UK
| | - Patrick Tan
- Duke-NUS Medical School, Singapore, Singapore
| | - Takaki Yoshikawa
- Department of Gastric Surgery, National Cancer Center Hospital, Tokyo, Japan ,Department of Gastrointestinal Surgery, Kanagawa Cancer Center Hospital, Yokohama, Japan
| | - Tomio Arai
- Department of Pathology, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, Tokyo, Japan
| | - Heike I. Grabsch
- Department of Pathology, GROW School for Oncology and Developmental Biology, Maastricht University Medical Center+, P. Debyelaan 25, 6229 HX Maastricht, The Netherlands ,Division of Pathology and Data Analytics, Leeds Institute of Medical Research at St. James’s, University of Leeds, Leeds, UK
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19
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Díaz Del Arco C, Estrada Muñoz L, Molina Roldán E, Cerón Nieto MÁ, Ortega Medina L, García Gómez de Las Heras S, Fernández Aceñero MJ. Immunohistochemical classification of gastric cancer based on new molecular biomarkers: a potential predictor of survival. Virchows Arch 2018; 473:687-695. [PMID: 30140949 DOI: 10.1007/s00428-018-2443-9] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2018] [Revised: 08/11/2018] [Accepted: 08/15/2018] [Indexed: 12/17/2022]
Abstract
Several classification systems have been described for stratifying patients with gastric carcinoma (GC). However, their prognostic value is low, and there is an urgent need for identification of molecular markers and development of new classifications. Retrospective study of 206 cases of GC diagnosed and surgically resected in our hospital between 2000 and 2017. Clinicopathological features of all cases were assessed and tissue microarrays were constructed for immunohistochemical (IHC) study. Patients were stratified based on IHC results. Mean patient age was 71 years and most patients were male (54.6%). Most tumors were located in the gastric antrum and body, and they were mostly fungoid or ulcerative lesions. GC were mainly intestinal-type tumors and 60.3% were diagnosed at pT3. 56.2% of patients showed recurrences and 29.4% died due to GC. According to our IHC classification, 23.5% of tumors showed microsatellite instability, 6% were E-cadherin negative, 53.5% were stable-p53 not overexpressed, and 17% were stable with p53 overexpression. IHC classification was significantly correlated with patient gender, gross morphology, Laurén classification, tumor necrosis, perineural infiltration, type of leading edge, and patient outcome. Multivariate analysis showed that IHC subtype was significantly and independently associated with overall survival, together with clinical symptoms, signet cell phenotype, tumor grade and vessel invasion. The application of IHC classifications based on molecular biomarkers in clinical practice can aid in the stratification of GC patients. More studies are needed to evaluate the reproducibility and clinical significance of these classifications.
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Affiliation(s)
- Cristina Díaz Del Arco
- Department of Surgical Pathology, Hospital Clínico San Carlos, 28040, Madrid, Spain.
- Complutense University of Madrid, Madrid, Spain.
| | - Lourdes Estrada Muñoz
- Department of Surgical Pathology, Hospital Rey Juan Carlos, Madrid, Spain
- Rey Juan Carlos University, Alcorcón, Madrid, Spain
| | - Elena Molina Roldán
- Department of Surgical Pathology, Hospital Clínico San Carlos, 28040, Madrid, Spain
| | | | - Luis Ortega Medina
- Department of Surgical Pathology, Hospital Clínico San Carlos, 28040, Madrid, Spain
- Complutense University of Madrid, Madrid, Spain
| | | | - Mª Jesús Fernández Aceñero
- Department of Surgical Pathology, Hospital Clínico San Carlos, 28040, Madrid, Spain
- Complutense University of Madrid, Madrid, Spain
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20
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Analysis of cyclin E co-expression genes reveals nuclear transcription factor Y subunit alpha is an oncogene in gastric cancer. Chronic Dis Transl Med 2018; 5:44-52. [PMID: 30993263 PMCID: PMC6449734 DOI: 10.1016/j.cdtm.2018.07.003] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2017] [Indexed: 12/12/2022] Open
Abstract
Objective To explore genes potentially co-expressed with cyclin E in gastric cancer and discover possible targets for gastric cancer treatment. Methods The Cancer Genome Atlas (TCGA) stomach adenocarcinoma sequencing data were used to predict genes co-expressed with cyclin E. Co-expression genes predicted by cBioPortal online analysis with Pearson correlation coefficient ≥0.4 were analyzed by gene ontology (GO) enrichment annotation using the PANTHER online platform (Ver. 7). Interactions between proteins encoded by these genes were analyzed using the STRING online platform (Ver. 10.5) and Cytoscape software (Ver. 3.5.1). Genes displaying a high degree of connection were analyzed by transcription factor enrichment prediction using FunRich software (Ver. 3). The significant transcription factor and cyclin E expression levels and their impact on gastric cancer progression were analyzed by Western blotting and Kaplan–Meier survival curve analysis. Results After filtering the co-expression gene prediction results, 78 predicted genes that included 73 protein coding genes and 5 non-coding genes with Pearson correlation coefficient ≥0.4 were selected. The expressions of the genes were considered to be correlated with cyclin E expression. Among the 78 genes co-expressed with cyclin E, 19 genes at the central of the regulatory network associated with cyclin E were discovered. Nuclear transcription factor Y subunit alpha (NF-YA) was identified as a significant transcription factor associated with cyclin E co-expressing genes. Analysis of specimen donors’ clinical records revealed that high expression of NF-YA tended to be associated with increased cyclin E expression. The expression of both was associated with progression of gastric cancer. Western blotting results showed that compared with normal tissues, NF-YA and cyclin E were highly expressed in tumor tissues (P < 0.001). Survival curve analysis clearly demonstrated relatively poor overall survival of gastric cancer patients with high cyclin E or high NF-YA expression level, compared to patients with low cyclin E or NF-YA expression (P < 0.05). Conclusions NF-YA may promote gastric cancer progression by increasing the transcription of cyclin E and other cell cycle regulatory genes. NF-YA might be a potential therapeutically useful prognostic factor for gastric cancer.
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21
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Balázs M, Koroknai V, Szász I, Ecsedi S. Detection of CCND1 Locus Amplification by Fluorescence In Situ Hybridization. Methods Mol Biol 2018; 1726:85-100. [PMID: 29468546 DOI: 10.1007/978-1-4939-7565-5_9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/08/2023]
Abstract
It is well known that chromosomal aberrations of tumors are associated with the initiation and progression of malignancy. Fluorescence in situ hybridization (FISH) is a powerful, rapid method to detect chromosome copy number and structural alterations in tissue sections, chromosome, or interphase cellular preparations via hybridization of complementary probe sequences. The technique is based on the complementary nature of DNA double strands, which allows fluorescently labeled DNA probes to be used as probes to label the complementary sequences of target cells, chromosomes, and tissues. FISH technique has many applications, including basic gene mapping, used in pathological diagnosis to detect chromosome and gene copy number aberrations, translocations, microdeletions, and duplications. For the recognition of gene amplifications and deletions, locus-specific probes that are collections of one or a few cloned DNA sequences are routinely used. Multiplex-FISH (M-FISH) technique visualizes all chromosomes with different colors using spectrally distinct fluorophores for each chromosome in one experiment to detect numerical and structural alterations of chromosomes obtained from tumor cells. Recently many of the gene-specific probes are commercially available.
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Affiliation(s)
- Margit Balázs
- Department of Preventive Medicine, Faculty of Public Health, University of Debrecen, Debrecen, Hungary.
| | - Viktória Koroknai
- MTA-DE Public Health Research Group, University of Debrecen, Debrecen, Hungary
| | - István Szász
- MTA-DE Public Health Research Group, University of Debrecen, Debrecen, Hungary
| | - Szilvia Ecsedi
- MTA-DE Public Health Research Group, University of Debrecen, Debrecen, Hungary
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22
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Ren W, Li W, Wang D, Hu S, Suo J, Ying X. Combining multi-dimensional data to identify key genes and pathways in gastric cancer. PeerJ 2017; 5:e3385. [PMID: 28603669 PMCID: PMC5463969 DOI: 10.7717/peerj.3385] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2017] [Accepted: 05/06/2017] [Indexed: 12/22/2022] Open
Abstract
Gastric cancer is an aggressive cancer that is often diagnosed late. Early detection and treatment require a better understanding of the molecular pathology of the disease. The present study combined data on gene expression and regulatory levels (microRNA, methylation, copy number) with the aim of identifying key genes and pathways for gastric cancer. Data used in this study was retrieved from The Cancer Genomic Atlas. Differential analyses between gastric cancer and normal tissues were carried out using Limma. Copy number alterations were identified for tumor samples. Bimodal filtering of differentially expressed genes (DEGs) based on regulatory changes was performed to identify candidate genes. Protein–protein interaction networks for candidate genes were generated by Cytoscape software. Gene ontology and pathway analyses were performed, and disease-associated network was constructed using the Agilent literature search plugin on Cytoscape. In total, we identified 3602 DEGs, 251 differentially expressed microRNAs, 604 differential methylation-sites, and 52 copy number altered regions. Three groups of candidate genes controlled by different regulatory mechanisms were screened out. Interaction networks for candidate genes were constructed consisting of 415, 228, and 233 genes, respectively, all of which were enriched in cell cycle, P53 signaling, DNA replication, viral carcinogenesis, HTLV-1 infection, and progesterone mediated oocyte maturation pathways. Nine hub genes (SRC, KAT2B, NR3C1, CDK6, MCM2, PRKDC, BLM, CCNE1, PARK2) were identified that were presumed to be key regulators of the networks; seven of these were shown to be implicated in gastric cancer through disease-associated network construction. The genes and pathways identified in our study may play pivotal roles in gastric carcinogenesis and have clinical significance.
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Affiliation(s)
- Wu Ren
- Department of Gastrointestinal Surgery, The First Hospital of Jilin University, Changchun, China.,Beijing Institute of Basic Medical Sciences, Beijing, China
| | - Wei Li
- Department of Gastrointestinal Surgery, The First Hospital of Jilin University, Changchun, China
| | - Daguang Wang
- Department of Gastrointestinal Surgery, The First Hospital of Jilin University, Changchun, China
| | - Shuofeng Hu
- Beijing Institute of Basic Medical Sciences, Beijing, China
| | - Jian Suo
- Department of Gastrointestinal Surgery, The First Hospital of Jilin University, Changchun, China
| | - Xiaomin Ying
- Beijing Institute of Basic Medical Sciences, Beijing, China
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