Association of autophagy status with amount of Fusobacterium nucleatum in colorectal cancer
Year: 2019
Type: article
Abstract: Fusobacterium nucleatum (F. nucleatum), which has been associated with colorectal carcinogenesis, can impair anti‐tumour immunity, and actively invade colon epithelial cells. Considering the critical role of autophagy in host defence against microorganisms, we hypothesised that autophagic activity of tumour cells might influence the amount of F. nucleatum in colorectal cancer tissue. Using 724 rectal and colon cancer cases within the Nurses' Health Study and the Health Professionals Follow‐up Study, we evaluated autophagic activity of tumour cells by immunohistochemical analyses of BECN1 (beclin 1), MAP1LC3 (LC3), and SQSTM1 (p62) expression. We measured the amount of F. nucleatum DNA in tumour tissue by quantitative polymerase chain reaction (PCR). We conducted multivariable ordinal logistic regression analyses to examine the association of tumour BECN1, MAP1LC3, and SQSTM1 expression with the amount of F. nucleatum, adjusting for potential confounders, including microsatellite instability status; CpG island methylator phenotype; long‐interspersed nucleotide element‐1 methylation; and KRAS, BRAF, and PIK3CA mutations. Compared with BECN1‐low cases, BECN1‐intermediate and BECN1‐high cases were associated with lower amounts of F. nucleatum with odds ratios (for a unit increase in three ordinal categories of the amount of F. nucleatum) of 0.54 (95% confidence interval, 0.29–0.99) and 0.31 (95% confidence interval, 0.16–0.60), respectively (Ptrend < 0.001 across ordinal BECN1 categories). Tumour MAP1LC3 and SQSTM1 levels were not significantly associated with the amount of F. nucleatum (Ptrend > 0.06). Tumour BECN1, MAP1LC3, and SQSTM1 levels were not significantly associated with patient survival (Ptrend > 0.10). In conclusion, tumour BECN1 expression is inversely associated with the amount of F. nucleatum in colorectal cancer tissue, suggesting a possible role of autophagy in the elimination of invasive microorganisms. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Source: The Journal of Pathology
DOI: 10.1002/path.5381
Authors: Koichiro Haruki, Keisuke Kosumi, Tsuyoshi Hamada, Tyler S Twombly, Juha P Väyrynen, Sun A Kim, Yohei Masugi, Zhi Rong Qian, Kosuke Mima, Yoshifumi Baba, Annacarolina da Silva, Jennifer Borowsky, Kota Arima, Kenji Fujiyoshi, Mai Chan Lau, Peilong Li, Chunguang Guo, Yang Chen, Mingyang Song, Jonathan A Nowak, Reiko Nishihara, Katsuhiko Yanaga, Xuehong Zhang, Kana Wu, Susan Bullman, Wendy S Garrett, Curtis Huttenhower, Jeffrey A Meyerhardt, Marios Giannakis, Andrew T Chan, Charles S Fuchs, Shuji Ogino
Institutions: Jikei University School of Medicine, Brigham and Women's Hospital, Harvard University, Oulu University Hospital, Dana-Farber Cancer Institute, University of Oulu, Sun Yat-sen University, The Seventh Affiliated Hospital of Sun Yat-sen University, Massachusetts General Hospital, Broad Institute, Yale Cancer Center, Yale University, Smilow Cancer Hospital, Dana-Farber/Harvard Cancer Center
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: American Association for Cancer Research, Conquer Cancer Foundation, William Caspar Graustein Memorial Fund, Entertainment Industry Foundation, Uehara Memorial Foundation, Friends of the Air Force Academy Library, Cancer Research UK, National Institutes of Health, Stand Up To Cancer, Australia Awards, Japan Society for the Promotion of Science, National Cancer Institute, National Institute of Diabetes and Digestive and Kidney Diseases
Awards: G1076363423, Dana Farber/ Harvard Cancer Center SPORE in Gastrointestinal Cancer, G1160275816, G123082938, G1327305488, G148836555, G1791405362, Comprehensive analysis of gut microbiome and sarcopenia in gastrointestinal cancers, G2214254730, G2883192542, Fusobacterium nucleatum Confers Chemoresistance by Modulating Autophagy in Esophageal Squamous Cell Carcinoma, G3101773556, G3115249328, Dietary and Hormonal Determinants of Cancer in Women, G4138424162, G46527388, Mentored Patient-Oriented Research in Digestive Diseases, Analysis of microbiome and epigenetics for the development of novel biomarker in Gastrointestinal cancers, Development of the innovative new treatments targeting cancer metabolism utilizing large GI cancer cohorts, Prospective Studies of Diet and Cancer in Men and Women, Comprehensive analysis of gut microbiome and epigenetic changes in esophageal cancer., Development of new colorectal cancer treatments through targeting the gut microbiota that influence antitumor immunity and the efficacy of cancer chemotherapies., G7442423963, G7467831316, G7632795048, Cancer Epidemiology Cohort in Male Health Professionals, Lifestyle, genetics and colonoscopy for colorectal cancer prevention, G9000000635, G9000005974, G9000030738, G9000031644, G9000043482, G9000050131, G9000099730, G9000134288, G9000176325, G9000184009, Center for the Study of Inflammatory Bowel Disease at Massachusetts General Hospital, G914912716
OpenAlex ID: W2996913923