基于双样本孟德尔随机化探究食源性致病菌与胃肠道癌症转移的相关性
Exploring the Correlation between Foodborne Pathogens and Gastrointestinal Cancer Metastasis Based on Two-Sample Mendelian Randomisation
DOI: 10.12677/amb.2025.141003, PDF,    国家自然科学基金支持
作者: 郑浩东:上海理工大学健康科学与工程学院,上海;赵兴贺, 陈哲逸, 沈立松*, 杨俊瑶*:上海交通大学医学院附属新华医院检验科,上海
关键词: 食源性致病菌孟德尔随机化胃肠道癌症癌症转移Foodborne Pathogenic Bacteria Mendelian Randomization Gastrointestinal Cancer Cancer Metastasis
摘要: 研究利用孟德尔随机化法(Mendelian randomization, MR)分析了几种食源性病原体与白细胞分化抗原44 (Cluster of differentiation 44, CD44)之间的关联,CD44抗原是胃肠道癌症发展和转移的标志物。该研究从综合流行病学数据库(IEU)、芬兰基因数据库(FinnGen)和英国生物数据库(UK Biobank)获得了全基因组关联研究(Genome-wide association studies, GWAS)数据,并主要使用反方差加权(Inverse-variance weighting, IVW)等统计方法分析了相关性。同时还进行了敏感性分析,以提高结果的可靠性。研究结果表明,幽门螺旋杆菌与CD44抗原呈显著正相关,而小肠结肠耶尔森氏菌与CD44抗原呈显著性负相关,因此研究判断幽门螺旋杆菌会促进癌症的发生和转移,而小肠结肠耶尔森氏菌可抑制癌细胞的发展和转移。然而,其余细菌种类没有发现明显的相关性。部分食源性致病菌可能会促进胃肠道癌症的转移,如幽门螺旋杆菌。但还有些可能抑制了癌细胞的转移,表明背后可能有更复杂的生理机制。
Abstract: This study used Mendelian randomization (MR) to analyze the association between several foodborne pathogens and the Cluster of Differentiation 44 (CD44) antigen, a marker of gastrointestinal cancer development and metastasis. The study obtained genome-wide association studies (GWAS) data from Integrative Epidemiology Unit (IEU), FinnGen and UK Biobank and analyzed the correlation mainly using statistical methods such as inverse-variance weighted (IVW). Sensitivity analyses were also carried out to improve the reliability of the results. The results of the study showed that Helicobacter pylori showed a significant positive correlation with CD44 antigen; Yersinia enterocolitica showed a significant negative correlation with CD44 antigen; therefore, we judged that Helicobacter pylori promotes cancer development and metastasis, and Yersinia enterocolitica inhibits cancer cell development and metastasis. However, no significant correlation was found for the remaining bacterial species. Some foodborne pathogens, such as Helicobacter pylori, can promote the metastasis of gastrointestinal cancers. However, others can inhibit the metastasis of cancer cells, suggesting that there may be a more complex physiological mechanism involved.
文章引用:郑浩东, 赵兴贺, 陈哲逸, 沈立松, 杨俊瑶. 基于双样本孟德尔随机化探究食源性致病菌与胃肠道癌症转移的相关性[J]. 微生物前沿, 2025, 14(1): 16-24. https://doi.org/10.12677/amb.2025.141003

参考文献

[1] Franz, C.M.A.P., den Besten, H.M.W., Böhnlein, C., Gareis, M., Zwietering, M.H. and Fusco, V. (2018) Microbial Food Safety in the 21st Century: Emerging Challenges and Foodborne Pathogenic Bacteria. Trends in Food Science & Technology, 81, 155-158. [Google Scholar] [CrossRef
[2] Abdallah, M., Benoliel, C., Drider, D., Dhulster, P. and Chihib, N. (2014) Biofilm Formation and Persistence on Abiotic Surfaces in the Context of Food and Medical Environments. Archives of Microbiology, 196, 453-472. [Google Scholar] [CrossRef] [PubMed]
[3] Somda, N.S., Tankoano, A., Métuor-Dabiré, A., Kaboré, D., Bonkoungou, J.O.I., Kpoda, D.S., et al. (2023) A Systematic Review and Meta-Analysis of Antibiotic Resistance of Foodborne Pathogenic Bacteria in West Africa between 2010 and 2020. Journal of Food Protection, 86, Article 100061. [Google Scholar] [CrossRef] [PubMed]
[4] Petrucci, S., Costa, C., Broyles, D., Dikici, E., Daunert, S. and Deo, S. (2021) On-Site Detection of Food and Waterborne Bacteria—Current Technologies, Challenges, and Future Directions. Trends in Food Science & Technology, 115, 409-421. [Google Scholar] [CrossRef] [PubMed]
[5] Beuchat, L.R., Kim, H., Gurtler, J.B., Lin, L., Ryu, J. and Richards, G.M. (2009) Cronobacter Sakazakii in Foods and Factors Affecting Its Survival, Growth, and Inactivation. International Journal of Food Microbiology, 136, 204-213. [Google Scholar] [CrossRef] [PubMed]
[6] Zhong, D., Wang, Z., Ye, Z., Wang, Y. and Cai, X. (2024) Cancer-Derived Exosomes as Novel Biomarkers in Metastatic Gastrointestinal Cancer. Molecular Cancer, 23, Article No. 67. [Google Scholar] [CrossRef] [PubMed]
[7] Huang, J., Lucero-Prisno, D.E., Zhang, L., Xu, W., Wong, S.H., Ng, S.C., et al. (2023) Updated Epidemiology of Gastrointestinal Cancers in East Asia. Nature Reviews Gastroenterology & Hepatology, 20, 271-287. [Google Scholar] [CrossRef] [PubMed]
[8] LaCourse, K.D., Johnston, C.D. and Bullman, S. (2021) The Relationship between Gastrointestinal Cancers and the Microbiota. The Lancet Gastroenterology & Hepatology, 6, 498-509. [Google Scholar] [CrossRef] [PubMed]
[9] Kazemi, Y., Dehghani, S., Nosrati, R., Taghdisi, S.M., Abnous, K., Alibolandi, M., et al. (2022) Recent Progress in the Early Detection of Cancer Based on CD44 Biomarker; Nano-Biosensing Approaches. Life Sciences, 300, Article 120593. [Google Scholar] [CrossRef] [PubMed]
[10] Gomari, M.M., Farsimadan, M., Rostami, N., Mahmoudi, Z., Fadaie, M., Farhani, I., et al. (2021) CD44 Polymorphisms and Its Variants, as an Inconsistent Marker in Cancer Investigations. Mutation Research/Reviews in Mutation Research, 787, Article 108374. [Google Scholar] [CrossRef] [PubMed]
[11] da Cunha, C.B., Klumpers, D.D., Koshy, S.T., Weaver, J.C., Chaudhuri, O., Seruca, R., et al. (2016) CD44 Alternative Splicing in Gastric Cancer Cells Is Regulated by Culture Dimensionality and Matrix Stiffness. Biomaterials, 98, 152-162. [Google Scholar] [CrossRef] [PubMed]
[12] Cheng, Q., Zheng, H., Li, M., Wang, H., Guo, X., Zheng, Z., et al. (2022) LGR4 Cooperates with PrPc to Endow the Stemness of Colorectal Cancer Stem Cells Contributing to Tumorigenesis and Liver Metastasis. Cancer Letters, 540, Article 215725. [Google Scholar] [CrossRef] [PubMed]
[13] Ikenaga, N., Ohuchida, K., Mizumoto, K., Cui, L., Kayashima, T., Morimatsu, K., et al. (2010) CD10+ Pancreatic Stellate Cells Enhance the Progression of Pancreatic Cancer. Gastroenterology, 139, 1041-1051.E8. [Google Scholar] [CrossRef] [PubMed]
[14] Artells, R., Moreno, I., Díaz, T., Martínez, F., Gel, B., Navarro, A., et al. (2010) Tumour CD133 mRNA Expression and Clinical Outcome in Surgically Resected Colorectal Cancer Patients. European Journal of Cancer, 46, 642-649. [Google Scholar] [CrossRef] [PubMed]
[15] Sanderson, E., Glymour, M.M., Holmes, M.V., Kang, H., Morrison, J., Munafò, M.R., et al. (2022) Mendelian Randomization. Nature Reviews Methods Primers, 2, Article No. 6. [Google Scholar] [CrossRef] [PubMed]
[16] Wang, H., Reid, B.M., Richmond, R.C., Lane, J.M., Saxena, R., Gonzalez, B.D., et al. (2024) Impact of Insomnia on Ovarian Cancer Risk and Survival: A Mendelian Randomization Study. eBioMedicine, 104, Article 105175. [Google Scholar] [CrossRef] [PubMed]
[17] Zhang, C., Jian, L., Li, X., Guo, W., Deng, W., Hu, X., et al. (2024) Mendelian Randomization Analysis of the Brain, Cerebrospinal Fluid, and Plasma Proteome Identifies Potential Drug Targets for Attention Deficit Hyperactivity Disorder. eBioMedicine, 105, Article 105197. [Google Scholar] [CrossRef] [PubMed]
[18] Kurki, M.I., Karjalainen, J., Palta, P., Sipilä, T.P., Kristiansson, K., Donner, K.M., et al. (2023) FinnGen Provides Genetic Insights from a Well-Phenotyped Isolated Population. Nature, 613, 508-518. [Google Scholar] [CrossRef] [PubMed]
[19] Elsworth, B., Lyon, M., Alexander, T., Liu, Y., Matthews, P., Hallett, J., et al. (2020) The MRC IEU OpenGWAS Data Infrastructure. Preprint. [Google Scholar] [CrossRef
[20] Sun, B.B., Maranville, J.C., Peters, J.E., Stacey, D., Staley, J.R., Blackshaw, J., et al. (2018) Genomic Atlas of the Human Plasma Proteome. Nature, 558, 73-79. [Google Scholar] [CrossRef] [PubMed]
[21] Boef, A.G.C., Dekkers, O.M. and Le Cessie, S. (2015) Mendelian Randomization Studies: A Review of the Approaches Used and the Quality of Reporting. International Journal of Epidemiology, 44, 496-511. [Google Scholar] [CrossRef] [PubMed]
[22] Uche-Ikonne, O., Dondelinger, F. and Palmer, T. (2020) Software Application Profile: Bayesian Estimation of Inverse Variance Weighted and MR-Egger Models for Two-Sample Mendelian Randomization Studies—Mrbayes. International Journal of Epidemiology, 50, 43-49. [Google Scholar] [CrossRef
[23] Mishra, Y., Ranjan, A., Mishra, V., Chattaraj, A., Aljabali, A.A.A., El-Tanani, M., et al. (2024) The Role of the Gut Microbiome in Gastrointestinal Cancers. Cellular Signalling, 115, Article 111013. [Google Scholar] [CrossRef] [PubMed]
[24] Cheng, S., Han, Z., Dai, D., Li, F., Zhang, X., Lu, M., et al. (2024) Multi-Omics of the Gut Microbial Ecosystem in Patients with Microsatellite-Instability-High Gastrointestinal Cancer Resistant to Immunotherapy. Cell Reports Medicine, 5, Article 101355. [Google Scholar] [CrossRef] [PubMed]
[25] Zha, L., Garrett, S. and Sun, J. (2019) Salmonella Infection in Chronic Inflammation and Gastrointestinal Cancer. Diseases, 7, Article 28. [Google Scholar] [CrossRef] [PubMed]
[26] Yoo, H.W., Hong, S.J. and Kim, S.H. (2024) Helicobacter Pylori Treatment and Gastric Cancer Risk after Endoscopic Resection of Dysplasia: A Nationwide Cohort Study. Gastroenterology, 166, 313-322.E3. [Google Scholar] [CrossRef] [PubMed]
[27] Lia, Z., Wang, J., Wang, Z. and Xu, Y. (2023) Towards an Optimal Model for Gastric Cancer Peritoneal Metastasis: Current Challenges and Future Directions. eBioMedicine, 92, Article 104601. [Google Scholar] [CrossRef] [PubMed]
[28] Polk, D.B. and Peek, R.M. (2010) Helicobacter pylori: Gastric Cancer and Beyond. Nature Reviews Cancer, 10, 403-414. [Google Scholar] [CrossRef] [PubMed]
[29] Shmuely, H., Passaro, D., Figer, A., Niv, Y., Pitlik, S., Samra, Z., et al. (2001) Relationship between Helicobacter pylori CagA Status and Colorectal Cancer. The American Journal of Gastroenterology, 96, 3406-3410.
[30] Liu, L., Sheng, X., Shuai, T., Zhao, Y., Li, B. and Li, Y. (2018) Helicobacter pylori Promotes Invasion and Metastasis of Gastric Cancer by Enhancing Heparanase Expression. World Journal of Gastroenterology, 24, 4565-4577. [Google Scholar] [CrossRef] [PubMed]
[31] Chan, A.O. (2003) Promoter Methylation of E-Cadherin Gene in Gastric Mucosa Associated with Helicobacter Pylori Infection and in Gastric Cancer. Gut, 52, 502-506. [Google Scholar] [CrossRef] [PubMed]
[32] Cebula, A.V. (2020) Yersinia-Mediated Colorectal Cancer Cell Death. MS Thesis, The University of Texas Health Science Center at San Antonio.
[33] Wang, M., Song, X., Liu, X., Ma, C., Ma, J. and Shi, L. (2024) Engineered Oncolytic Bacteria for Malignant Solid Tumor Treatment. Interdisciplinary Medicine, 2, e20240005. [Google Scholar] [CrossRef
[34] Ji, J., Sundquist, J. and Sundquist, K. (2018) Cholera Vaccine Use Is Associated with a Reduced Risk of Death in Patients with Colorectal Cancer: A Population-Based Study. Gastroenterology, 154, 86-92.E1. [Google Scholar] [CrossRef] [PubMed]
[35] Doulberis, M., Angelopoulou, K., Kaldrymidou, E., Tsingotjidou, A., Abas, Z., Erdman, S.E., et al. (2014) Cholera-Toxin Suppresses Carcinogenesis in a Mouse Model of Inflammation-Driven Sporadic Colon Cancer. Carcinogenesis, 36, 280-290. [Google Scholar] [CrossRef] [PubMed]
[36] Viallet, J., Sharoni, Y., Frucht, H., Jensen, R.T., Minna, J.D. and Sausville, E.A. (1990) Cholera Toxin Inhibits Signal Transduction by Several Mitogens and the in Vitro Growth of Human Small-Cell Lung Cancer. Journal of Clinical Investigation, 86, 1904-1912. [Google Scholar] [CrossRef] [PubMed]
[37] Yusuf, K., Sampath, V. and Umar, S. (2023) Bacterial Infections and Cancer: Exploring This Association and Its Implications for Cancer Patients. International Journal of Molecular Sciences, 24, Article 3110.
[38] Chen, C., Zhao, S., Karnad, A. and Freeman, J.W. (2018) The Biology and Role of CD44 in Cancer Progression: Therapeutic Implications. Journal of Hematology & Oncology, 11, Article No. 64. [Google Scholar] [CrossRef] [PubMed]
[39] Puré, E. and Cuff, C.A. (2001) A Crucial Role for CD44 in Inflammation. Trends in Molecular Medicine, 7, 213-221. [Google Scholar] [CrossRef] [PubMed]
[40] Matsumura, Y. and Tarin, D. (1992) Significance of CD44 Gene Products for Cancer Diagnosis and Disease Evaluation. The Lancet, 340, 1053-1058. [Google Scholar] [CrossRef] [PubMed]