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Qiu J, Liu D, Wu C, Chen H, Xie J, Chen S, Wang Y, Zhou F, Fang J, Lai Q, Zhao R, Xie Y. Association between non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio and Helicobacter pylori infection. Sci Rep 2025; 15:12560. [PMID: 40221572 PMCID: PMC11993665 DOI: 10.1038/s41598-025-96851-5] [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: 01/02/2025] [Accepted: 04/01/2025] [Indexed: 04/14/2025] Open
Abstract
Evidence on the association between the non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) and Helicobacter pylori (H. pylori) infection remains limited. This study investigates this correlation based on the U.S. population. This cross-sectional research included data on 834 U.S. participants from the National Health and Nutrition Examination Survey 1999-2000. The association between the NHHR and H. pylori infection was examined using logistic regression models, restricted cubic spline (RCS) curve and subgroup analyses. Individuals with H. pylori infection exhibited significantly higher NHHR value. A significant positive association between NHHR and H. pylori infection was observed across all three models, even after adjusting for potential confounders, with a stronger association noted in males, individuals under 60 years of age, and non-Hispanic White participants. These findings suggest NHHR may act as a non-invasive biomarker for detecting H. pylori infection in U.S. populations.
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Affiliation(s)
- Jiayu Qiu
- Department of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
| | - Dingwei Liu
- Department of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
| | - Chengyun Wu
- Department of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
| | - Hao Chen
- Department of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
| | - Jinliang Xie
- Department of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
| | - Sihai Chen
- Department of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
| | - Youhua Wang
- Department of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
| | - Feng Zhou
- Department of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
| | - Jiasheng Fang
- Department of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
| | - Qirui Lai
- Huan Kui College of Nanchang University, Jiangxi Medical College, Nanchang University, Nanchang, 330006, Jiangxi Province, China
| | - Rulin Zhao
- Department of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China.
- Department of Clinical Laboratory, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China.
- Postdoctoral Innovation Practice Base, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China.
| | - Yong Xie
- Department of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China.
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Sun HT. Helicobacter pylori-related serum indicators: Cutting-edge advances to enhance the efficacy of gastric cancer screening. World J Gastrointest Oncol 2025; 17:100739. [PMID: 40092953 PMCID: PMC11866254 DOI: 10.4251/wjgo.v17.i3.100739] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2024] [Revised: 12/08/2024] [Accepted: 01/03/2025] [Indexed: 02/14/2025] Open
Abstract
Helicobacter pylori (H. pylori) infection induces pathological changes via chronic inflammation and virulence factors, thereby increasing the risk of gastric cancer development. Compared with invasive examination methods, H. pylori-related serum indicators are cost-effective and valuable for the early detection of gastric cancer (GC); however, large-scale clinical validation and sufficient understanding of the specific molecular mechanisms involved are lacking. Therefore, a comprehensive review and analysis of recent advances in this field is necessary. In this review, we systematically analyze the relationship between H. pylori and GC and discuss the application of new molecular biomarkers in GC screening. We also summarize the screening potential and application of anti-H. pylori immunoglobulin G and virulence factor-related serum antibodies for identifying GC risk. These indicators provide early warning of infection and enhance screening accuracy. Additionally, we discuss the potential combination of multiple screening indicators for the comprehensive analysis and development of emerging testing methods to improve the accuracy and efficiency of GC screening. Although this review may lack sufficient evidence due to limitations in existing studies, including small sample sizes, regional variations, and inconsistent testing methods, it contributes to advancing personalized precision medicine in high-risk populations and developing GC screening strategies.
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Affiliation(s)
- Hao-Tian Sun
- Cancer Institute, University College London, London WC1E 6BT, United Kingdom
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Barhoine M, Moustaoui F, Hammani O, Aghrouch M, Lemkhente Z, Belhabib Z, Bajaddoub Z, Touyar A, Aqoudad N, Rherissi B, El Kadmiri N, Idaghdour Y, Boubrik F, Belmouden A. The Effect of Helicobacter pylori Gene Combinations of cagA, cagE, virB11, vacA, and babA on the Outcome of Gastric Disease in a Southern Moroccan Population. Pathogens 2025; 14:279. [PMID: 40137764 PMCID: PMC11944658 DOI: 10.3390/pathogens14030279] [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: 01/28/2025] [Revised: 02/17/2025] [Accepted: 02/18/2025] [Indexed: 03/29/2025] Open
Abstract
Helicobacter pylori (H. pylori) possess an arsenal of virulence genes that makes them the main etiological factor in gastric diseases. In this study, 120 southern Moroccan patients who were dyspeptic were profiled to investigate the potential association between disease severity and the combination of multiple virulence genes. Gastric biopsies were taken from patients, followed by histopathological evaluation and genotyping of H. pylori using PCR. H. pylori was detected in 58.3% of cases, and genotypes were distributed as follows: oipA (94.3%), cagA (62.9%), virB11 (60%), babA (55.7%), dupA (54.3%), cagE (51.4%), iceA1 (31.4%), iceA2 (45.7%), vacA s2m2 (47.1%), vacA s1m1 (30%), and vacA s1m2 (7.1%). Statistically significant associations with males were observed for the cagA, cagE, and virB11 genes and multiple strain infections. Multivariate analysis revealed an association between cagE and heightened neutrophil activity, with an odds ratio (OR) of 4.99 (p = 0.03). The gene combination [cagA (+), cagE (+), virB11 (+), vacA s1m1, and babA (+)] emerged as a predictive factor for gastric cancer (OR = 11.10, p = 0.046), while the combination [cagA (-), cagE (-), virB11 (-), vacA s2m2, babA (+)] was associated with gastric atrophy (OR = 10.25, p = 0.016). Age (≤40 years) (OR = 5.87, p = 0.013) and moderate to severe bacterial density (OR = 15.38, p = 0.017) were identified as predictive factors for follicular gastritis. These findings underscore the significance of multigene profiling as a prognostic marker and emphasize the importance of age and sex in preventing adverse outcomes in severe gastric diseases.
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Affiliation(s)
- Mariama Barhoine
- Cell Biology and Molecular Genetics Laboratory, Faculty of Sciences, Ibnou Zohr University, Agadir 80000, Morocco; (M.B.); (F.B.)
| | - Fatima Moustaoui
- Cell Biology and Molecular Genetics Laboratory, Faculty of Sciences, Ibnou Zohr University, Agadir 80000, Morocco; (M.B.); (F.B.)
- Medical Analysis Laboratory, Regional Hospital Centre Hassan II, Agadir 80000, Morocco
| | - Omayma Hammani
- Cell Biology and Molecular Genetics Laboratory, Faculty of Sciences, Ibnou Zohr University, Agadir 80000, Morocco; (M.B.); (F.B.)
| | - Mohamed Aghrouch
- Medical Analysis Laboratory, Regional Hospital Centre Hassan II, Agadir 80000, Morocco
- Medical-Surgical, Biomedicine and Infectiology Laboratory, Faculty of Medicine and Pharmacy, Ibnou Zohr University, Agadir 80000, Morocco;
| | - Zohra Lemkhente
- Medical-Surgical, Biomedicine and Infectiology Laboratory, Faculty of Medicine and Pharmacy, Ibnou Zohr University, Agadir 80000, Morocco;
| | | | - Zineb Bajaddoub
- Gastroenterology Unit, Mokhtar Soussi Hospital, Taroudant 83000, Morocco
| | - Anass Touyar
- Gastroenterology Unit, Hassan II Hospital, Agadir 80000, Morocco
| | - Nourdin Aqoudad
- Faculty of Medicine and Pharmacy of Agadir, Ibnou Zohr University, Agadir 80000, Morocco
| | - Bouchra Rherissi
- Cell Biology and Molecular Genetics Laboratory, Faculty of Sciences, Ibnou Zohr University, Agadir 80000, Morocco; (M.B.); (F.B.)
| | - Nadia El Kadmiri
- Geo-Bio-Environment Engineering and Innovation Laboratory, Polydisciplinary Faculty, Ibnou Zohr University, Taroudant 83000, Morocco
| | - Youssef Idaghdour
- Center for Genomics and Systems Biology, New York University Abu Dhabi, Abu Dhabi P.O. Box 129188, United Arab Emirates;
| | - Fatima Boubrik
- Cell Biology and Molecular Genetics Laboratory, Faculty of Sciences, Ibnou Zohr University, Agadir 80000, Morocco; (M.B.); (F.B.)
| | - Ahmed Belmouden
- Cell Biology and Molecular Genetics Laboratory, Faculty of Sciences, Ibnou Zohr University, Agadir 80000, Morocco; (M.B.); (F.B.)
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Abbas M, Tangney M. The oncobiome; what, so what, now what? MICROBIOME RESEARCH REPORTS 2025; 4:16. [PMID: 40207280 PMCID: PMC11977386 DOI: 10.20517/mrr.2024.89] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/13/2024] [Revised: 02/14/2025] [Accepted: 02/21/2025] [Indexed: 04/11/2025]
Abstract
Microbial communities inhabiting various body sites play critical roles in the initiation, progression, and treatment of cancer. The gut microbiota, a highly diverse microbial ecosystem, interacts with immune cells to modulate inflammation and immune surveillance, influencing cancer risk and therapeutic outcomes. Local tissue microbiota may impact the transition from premalignant states to malignancy. Characterization of the intratumoral microbiota increasingly reveals distinct microbiomes that may influence tumor growth, immune responses, and treatment efficacy. Various bacteria species have been reported to modulate cancer therapies through mechanisms such as altering drug metabolism and shaping the tumor microenvironment (TME). For instance, gut or intratumoral bacterial enzymatic activity can convert prodrugs into active forms, enhancing therapeutic effects or, conversely, inactivating small-molecule chemotherapeutics. Specific bacterial species have also been linked to improved responses to immunotherapy, underscoring the microbiome's role in treatment outcomes. Furthermore, unique microbial signatures in cancer patients, compared with healthy individuals, demonstrate the diagnostic potential of microbiota. Beyond the gut, tumor-associated and local microbiomes also affect therapy by influencing inflammation, tumor progression, and drug resistance. This review explores the multifaceted relationships between microbiomes and cancer, focusing on their roles in modulating the TME, immune activation, and treatment efficacy. The diagnostic and therapeutic potential of bacterial members of microbiota represents a promising avenue for advancing precision oncology and improving patient outcomes. By leveraging microbial biomarkers and interventions, new strategies can be developed to optimize cancer diagnosis and treatment.
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Affiliation(s)
- Munawar Abbas
- APC Microbiome Ireland, University College Cork, Cork, T12 YT20, Ireland
- Cancer Research@UCC, University College Cork, Cork, T12 XF62, Ireland
| | - Mark Tangney
- APC Microbiome Ireland, University College Cork, Cork, T12 YT20, Ireland
- Cancer Research@UCC, University College Cork, Cork, T12 XF62, Ireland
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Pérez-Navarro Y, Salinas-Vera YM, López-Camarillo C, Figueroa-Angulo EE, Alvarez-Sánchez ME. The role of long non-coding RNA NORAD in digestive system tumors. Noncoding RNA Res 2025; 10:55-62. [PMID: 39296642 PMCID: PMC11406672 DOI: 10.1016/j.ncrna.2024.09.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2024] [Revised: 08/28/2024] [Accepted: 09/01/2024] [Indexed: 09/21/2024] Open
Abstract
In recent years, it has been discovered that the expression of long non-coding RNAs is highly deregulated in several types of cancer and contributes to its progression and development. Recently, it has been described that in tumors of the digestive system, such as colorectal cancer, pancreatic cancer, and gastric cancer, DNA damage-activated lncRNA (NORAD) was frequently up-regulated. The purpose of this review is to elucidate the functions of NORAD in tumors of the digestive system, emphasizing its involvement in important cellular processes such as invasion, metastasis, proliferation, and apoptosis. NORAD acts as a ceRNA (competitive endogenous RNA) that sponges microRNAs and regulates the expression of target genes involved in tumorigenesis. Thus, the mechanisms underlying the effects of NORAD are complex and involve multiple signaling pathways. This review consolidates current knowledge on the role of NORAD in digestive cancers and highlights the need for further research to explore its potential as a therapeutic target. Understanding the intricate functions of NORAD could elucidate the way for innovative approaches to cancer treatment.
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Affiliation(s)
- Yussel Pérez-Navarro
- Posgrado en Ciencias Genómicas, Laboratorio de Patogénesis Celular y Molecular Humana y Veterinaria, Universidad Autónoma de la Ciudad de México, Ciudad de México, CDMX, Mexico
| | - Yarely M. Salinas-Vera
- Centro Nacional de Identificación Humana, Comisión Nacional de Búsqueda, Secretaría de Gobernación, Camino a Santa Teresa No 1679, Jardines del Pedregal, Ciudad de México, Mexico
| | - Cesar López-Camarillo
- Posgrado en Ciencias Genómicas, Laboratorio de Oncogenómica y Proteómica del cáncer, Universidad Autónoma de la Ciudad de México, Ciudad de México, Mexico
| | - Elisa Elvira Figueroa-Angulo
- Licenciatura en Ciencias Genómicas, Laboratorio de Patogénesis Celular y Molecular Humana y Veterinaria, Universidad Autónoma de la Ciudad de México, Mexico
| | - María Elizbeth Alvarez-Sánchez
- Posgrado en Ciencias Genómicas, Laboratorio de Patogénesis Celular y Molecular Humana y Veterinaria, Universidad Autónoma de la Ciudad de México, Ciudad de México, CDMX, Mexico
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Hayashi T, Sano K, Okada M, Muto M, Konishi I. Efficacy and Tolerability of Olaparib Plus Paclitaxel in Patients with Gastric Cancer Associated with Hereditary Breast and Ovarian Cancer. Curr Oncol 2024; 31:6723-6734. [PMID: 39590127 PMCID: PMC11592444 DOI: 10.3390/curroncol31110496] [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: 09/03/2024] [Revised: 10/24/2024] [Accepted: 10/25/2024] [Indexed: 11/28/2024] Open
Abstract
Helicobacter pylori, a gram-negative, flagellated, helical bacterium, is a common cause of chronic gastric infection worldwide. According to the World Health Organization, H. pylori infection, a specific carcinogenic factor, was the leading cause of gastric cancer (GC) in 2014 worldwide (80%). H. pylori infection causes GC in >98% of patients in East Asian countries, including Japan. However, only some types of GCs are associated with H. pylori infection. Previous clinical studies have revealed that the bacterium secretes cytotoxin-associated gene A antigen, which inhibits the nuclear translocation of the breast cancer susceptibility gene 1 and 2 (BRCA1/2), a factor involved in DNA damage repair. This indicated an association between hereditary breast and ovarian cancers (HBOCs) and the development of GC. However, the detailed mechanisms underlying the development of GC caused by H. pylori infection remain unclear. Using the information on hereditary cancers obtained based on cancer genomic medicine, this study revealed that the incidence of GC was high in families with HBOC, with a preponderance for men from families with HBOC. Furthermore, the use of poly-adenosine diphosphate-ribose polymerase inhibitors in patients with hereditary GC is considered safe and effective. This study provides substantial evidence for guiding the establishment of early treatment for patients with advanced-stage/metastatic GC who harbored BRCA1/2 mutations.
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Affiliation(s)
- Takuma Hayashi
- Cancer Medicine, National Hospital Organization Kyoto Medical Center, Fushimi-ku, Kyoto 612-8555, Kyoto, Japan
| | - Kenji Sano
- Pathological Division, Shinshu University Hospital, Matsumoto 390-0877, Nagano, Japan
| | - Mako Okada
- Cancer Medicine, National Hospital Organization Kyoto Medical Center, Fushimi-ku, Kyoto 612-8555, Kyoto, Japan
| | - Manabu Muto
- Medical Oncology, Kyoto University Hospital, Kyoto 612-8555, Kyoto, Japan
| | - Ikuo Konishi
- Cancer Medicine, National Hospital Organization Kyoto Medical Center, Fushimi-ku, Kyoto 612-8555, Kyoto, Japan
- Department of Medical Oncology, Kyoto University School of Medicine, Kyoto 606-8507, Kyoto, Japan
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Hayashi T, Sano K, Okada M, Ura T, Konishi I. Hereditary Gastric Cancer Is Linked With Hereditary Breast and Ovarian Cancer. World J Oncol 2024; 15:722-730. [PMID: 38993249 PMCID: PMC11236378 DOI: 10.14740/wjon1871] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2024] [Accepted: 05/17/2024] [Indexed: 07/13/2024] Open
Abstract
Background Helicobacter pylori (H. pylori), a bacterium which chronically infects the stomach of approximately half the world's population, is a risk factor for the development of gastric cancer (GC). However, the underlying mechanism whereby H. pylori infection induces GC development remains unclear. Intermittent injection of the H. pylori cytotoxin-associated gene A antigen (CagA) protein into its host cell inhibits nuclear translocation of BRCA1/BRCA2, DNA repair proteins involved in the development of breast cancer/ovarian cancer. Interestingly, hereditary breast and ovarian cancer (HBOC) syndrome is associated with GC development. Here, we aimed to clarify the molecular link between H. pylori infection, BRCA1/2 pathogenic variants (PVs), GC and higher GC incidence in HBOC families. Methods We retrospectively reviewed data from Japanese patients undergoing precision treatment using cancer genomic medicine. Results We found a higher GC incidence in HBOC families having germline pathogenic variants (GPVs) of BRCA1/2 (2.95% vs. 0.78% in non-HBOC families). Next, we found that 96.1% of H. pylori-infected patients received cancer genomic medicine for advanced GC, and > 16% advanced GC patients had gBRCA2 PVs. Furthermore, expressing wild-type BRCA1/2 in Gan mice (a mouse model of human GC) inhibited GC development. Thus, gBRAC1/2 PVs and H. pylori infection synergistically increase the risk of GC development. Conclusion Our study highlights the need to investigate the potential of therapeutic agents against BRCA1/2 PVs to avoid the development of GC in HBOC families. In addition, our results suggest that poly (ADP-ribose) polymerase (PARP) inhibitors could potentially inhibit GC development and progression with gBRCA1/2 PVs.
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Affiliation(s)
- Takuma Hayashi
- Cancer Medicine, National Hospital Organization Kyoto Medical Center, Kyoto 612-8555, Japan
| | - Kenji Sano
- Pathological Division, Shinshu University Hospital, Matsumoto, , Nagano 390-0877, Japan
| | - Mako Okada
- Cancer Medicine, National Hospital Organization Kyoto Medical Center, Kyoto 612-8555, Japan
| | - Takashi Ura
- Medical Oncology, National Hospital Organization Kyoto Medical Center, Kyoto 612-8555, Japan
| | - Ikuo Konishi
- Cancer Medicine, National Hospital Organization Kyoto Medical Center, Kyoto 612-8555, Japan
- Kyoto University School of Medicine, Kyoto 606-8507, Japan
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8
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Meliț LE, Mărginean CO, Borka Balas R. The Most Recent Insights into the Roots of Gastric Cancer. Life (Basel) 2024; 14:95. [PMID: 38255710 PMCID: PMC10817233 DOI: 10.3390/life14010095] [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: 11/29/2023] [Revised: 01/01/2024] [Accepted: 01/05/2024] [Indexed: 01/24/2024] Open
Abstract
Helicobacter pylori (H. pylori) is the most common bacterial infection worldwide, usually being acquired during childhood, and its persistence into adulthood represents one of the main contributors of gastric carcinogenesis. Based on these statements, it would be of great importance to know if the most early premalignant transformation occurs in children or later since, this would enable the development of effective anti-tumorigenesis strategies. The interplay between H. pylori virulence factors, the host's responses modified by this infection, and the gastric microecology are complex and eventually lead to the development of gastric cancer in susceptible individuals. Several biomarkers were identified as major contributors of this long-lasting process, such as pepsinogens, gastrin 17, lipid-, glucose- and iron-metabolism parameters, immunity players, aberrant bacterial DNA methylation, H. pylori virulence factors, and hallmarks of gastric dysbiosis. Several of these biomarkers were also identified in children with H. pylori infection, independently of the presence of premalignant lesions, which were also proven to be present in a subgroup of H. pylori-infected children, especially those carrying extremely virulent strains. Therefore, the most incipient premalignant gastric changes might indeed occur early during childhood, opening a promising research gate for further studies to delineate the border between infection and cancer.
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Affiliation(s)
| | - Cristina Oana Mărginean
- Department of Pediatrics I, “George Emil Palade” University of Medicine, Pharmacy, Sciences and Technology, Târgu Mureș, Gheorghe Marinescu Street, No. 38, 540136 Târgu Mureș, Romania; (L.E.M.)
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9
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Bandarian F, Razi F, Razzaghi Z, Rostami Nejad M, Arjmand B, Ahmadzadeh A. Network analysis of H. pylori effect on AGS human gastric adenocarcinoma cells gene expression profile. GASTROENTEROLOGY AND HEPATOLOGY FROM BED TO BENCH 2024; 17:415-421. [PMID: 40406433 PMCID: PMC12094504 DOI: 10.22037/ghfbb.v17i4.3023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/20/2024] [Accepted: 07/27/2024] [Indexed: 05/26/2025]
Abstract
Aim To better understand the molecular mechanism of Helicobacter pylori (H. pylori) in adenocarcinoma, the gene expression profile of AGS cells was analyzed by complementary study. Background Gastric cancer, as one of the most lethal malignancies in the world, is important to be studied in terms of biomarkers. On the other hand, Helicobacter pylori is one of the key risk factors in this type of disease. Methods In this cross-sectional study, we evaluated the seroprevalence of total and IgM anti-HAV antibodies of 254 institutionalized people with intellectual disabilities. Total and IgM anti-HAV antibodies of the blood samples of these people were determined by ELISA method. Protein-protein interaction (PPI) network analysis is a bioinformatic study with validation values for biomarker identification and clarification of molecular mechanisms. Cytoscape V 3.10.2 and its application identified potential central elements of the PPI network and its corresponding roles. Results GAPDH and P53 are the most promising candidates in this study. In addition, the microRNA signatures assessment provided more information about these biomarkers and added more value. Conclusion Consequently, a new outlook for the relationship between gastric cancer and H. pylori was explored based on the new key biomarkers.
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Affiliation(s)
- Fatemeh Bandarian
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Farideh Razi
- Diabetes Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Zahra Razzaghi
- Laser application in medical sciences research center, Shahid Beheshti University of medical sciences, Tehran, Iran
| | - Mohammad Rostami Nejad
- Celiac Disease and Gluten Related Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Babak Arjmand
- Cell Therapy and Regenerative Medicine Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
- Iranian Cancer Control Center (MACSA), Tehran, Iran
| | - Alireza Ahmadzadeh
- Proteomics Research Center, System Biology Institute, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Department of lab sciences, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Li Y, Xiong JB, Jie ZG, Xiong H. Hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit beta gene as a tumour suppressor in stomach adenocarcinoma. Front Oncol 2022; 12:1069875. [PMID: 36518312 PMCID: PMC9743170 DOI: 10.3389/fonc.2022.1069875] [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: 10/14/2022] [Accepted: 11/04/2022] [Indexed: 08/22/2023] Open
Abstract
BACKGROUND Stomach adenocarcinoma (STAD) is the most common type of gastric cancer. In this study, the functions and potential mechanisms of hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit beta (HADHB) in STAD were explored. METHODS Different bioinformatics analyses were performed to confirm HADHB expression in STAD. HADHB expression in STAD tissues and cells was also evaluated using western blot, qRT-PCR, and immunohistochemistry. Further, the viability, proliferation, colony formation, cell cycle determination, migration, and wound healing capacity were assessed, and the effects of HADHB on tumour growth, cell apoptosis, and proliferation in nude mice were determined. The upstream effector of HADHB was examined using bioinformatics analysis and dual luciferase reporter assay. GSEA was also employed for pathway enrichment analysis and the expression of Hippo-YAP pathway-related proteins was detected. RESULTS The expression of HADHB was found to be low in STAD tissues and cells. The upregulation of HADHB distinctly repressed the viability, proliferation, colony formation, cell cycle progression, migration, invasion, and wound healing of HGC27 cells, while knockdown of HADHB led to opposite effects. HADHB upregulation impeded tumour growth and cell proliferation, and enhanced apoptosis in nude mice. KLF4, whose expression was low in STAD, was identified as an upstream regulator of HADHB. KLF4 upregulation abolished the HADHB knockdown-induced tumour promoting effects in AGS cells. Further, HADHB regulates the Hippo-YAP pathway, which was validated using a pathway rescue assay. Low expression of KLF4 led to HADHB downregulation in STAD. CONCLUSION HADHB might function as a tumour suppressor gene in STAD by regulation the Hippo-YAP pathway.
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Affiliation(s)
- Yun Li
- Department of Digestive Surgery, Digestive Disease Hospital, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
- Gastrointestinal Surgical Institute of Nanchang University, Nanchang, Jiangxi, China
| | - Jian-Bo Xiong
- Department of Digestive Surgery, Digestive Disease Hospital, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
- Gastrointestinal Surgical Institute of Nanchang University, Nanchang, Jiangxi, China
| | - Zhi-Gang Jie
- Department of Digestive Surgery, Digestive Disease Hospital, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
- Gastrointestinal Surgical Institute of Nanchang University, Nanchang, Jiangxi, China
| | - Hui Xiong
- Department of Digestive Surgery, Digestive Disease Hospital, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
- Gastrointestinal Surgical Institute of Nanchang University, Nanchang, Jiangxi, China
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Shatila M, Thomas AS. Current and Future Perspectives in the Diagnosis and Management of Helicobacter pylori Infection. J Clin Med 2022; 11:jcm11175086. [PMID: 36079015 PMCID: PMC9456682 DOI: 10.3390/jcm11175086] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2022] [Revised: 08/24/2022] [Accepted: 08/25/2022] [Indexed: 12/03/2022] Open
Abstract
Helicobacter pylori (Hp) is a prevalent organism infecting almost half the global population. It is a significant concern, given its associated risk of gastric cancer, which is the third leading cause of cancer death globally. Infection can be asymptomatic or present with dyspeptic symptoms. It may also present with alarm symptoms in the case of progression to cancer. Diagnosis can be achieved non-invasively (breath tests, stool studies, or serology) or invasively (rapid urease test, biopsy, or culture). Treatment involves acid suppression and regimens containing several antibiotics and is guided by resistance rates. Eradication is essential, as it lowers the risk of complications and progression to cancer. Follow-up after eradication is similarly important, as the risk of cancer progression remains. There have been many recent advances in both diagnosis and treatment of Hp. In particular, biosensors may be effective diagnostic tools, and nanotechnology, vaccines, and potassium-competitive acid blockers may prove effective in enhancing eradication rates.
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12
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Luo Z, Luo Y, Xiao K. A-Kinase Interacting Protein 1 Promotes Cell Invasion and Stemness via Activating HIF-1α and β-Catenin Signaling Pathways in Gastric Cancer Under Hypoxia Condition. Front Oncol 2022; 11:798557. [PMID: 35355804 PMCID: PMC8959465 DOI: 10.3389/fonc.2021.798557] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2021] [Accepted: 12/23/2021] [Indexed: 01/16/2023] Open
Abstract
Background A-Kinase interacting protein 1 (AKIP1) relates to gastric cancer growth, metastasis, and prognosis, while its regulation on gastric cancer invasion and stemness under hypoxia microenvironment is not reported. Therefore, this study aimed to explore this topic to uncover AKIP1’s role in gastric cancer under hypoxia. Methods Gastric cancer cell lines AGS and MKN45 were cultured under hypoxia condition, then transfected with AKIP1 or negative control (NC) overexpression plasmid or AKIP1 or NC knockdown plasmid. Furthermore, rescue experiments were conducted by transfecting HIF-1α or β-catenin overexpression plasmid, combined with AKIP1 or NC knockdown plasmid. Afterward, cell invasion, CD133+ cell proportion, sphere number/1,000 cells, and HIF-1α and β-catenin pathways were measured. Results The invasive cell count, CD133+ cell proportion, and sphere number/1,000 cells were enhanced in both AGS cells and MKN45 cells under hypoxia, and AKIP1 expression was also elevated. AKIP1 knockdown inhibited cell invasion, CD133+ cell proportion, sphere number/1,000 cells, HIF-1α, vascular endothelial growth factor (VEGF), β-catenin, and calcium-binding protein (CBP) expressions in AGS cells and MKN45 cells under hypoxia, while AKIP1 overexpression presented with the opposite effect. Then, in rescue experiments, HIF-1α overexpression and β-catenin overexpression both promoted cell invasion, CD133+ cell proportion, and sphere number/1,000 cells, which also attenuated the effect of AKIP1 knockdown on these functions in AGS cells and MKN45 cells. Conclusion AKIP1 promotes cell invasion and stemness via activating HIF-1α and β-catenin signaling pathways in gastric cancer under hypoxia condition.
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Affiliation(s)
- Zhenqin Luo
- Department of Comprehensive Chemotherapy, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China
| | - Yuhang Luo
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital, The University of South China, Hengyang, China
| | - Ke Xiao
- Department of Gastroduodenal and Pancreatic Surgery, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China
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Altanbayar O, Amgalanbaatar A, Battogtokh C, Bayarjargal N, Belick D, Kohns Vasconcelos M, Mackenzie CR, Pfeffer K, Henrich B. Characterization of the cagA-gene in Helicobacter pylori in Mongolia and detection of two EPIYA-A enriched CagA types. Int J Med Microbiol 2022; 312:151552. [DOI: 10.1016/j.ijmm.2022.151552] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2021] [Revised: 01/28/2022] [Accepted: 02/22/2022] [Indexed: 11/30/2022] Open
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