TY - JOUR
T1 - Association of autophagy status with amount of Fusobacterium nucleatum in colorectal cancer
AU - Haruki, Koichiro
AU - Kosumi, Keisuke
AU - Hamada, Tsuyoshi
AU - Twombly, Tyler S.
AU - Väyrynen, Juha P.
AU - Kim, Sun A.
AU - Masugi, Yohei
AU - Qian, Zhi Rong
AU - Mima, Kosuke
AU - Baba, Yoshifumi
AU - da Silva, Annacarolina
AU - Borowsky, Jennifer
AU - Arima, Kota
AU - Fujiyoshi, Kenji
AU - Lau, Mai Chan
AU - Li, Peilong
AU - Guo, Chunguang
AU - Chen, Yang
AU - Song, Mingyang
AU - Nowak, Jonathan A.
AU - Nishihara, Reiko
AU - Yanaga, Katsuhiko
AU - Zhang, Xuehong
AU - Wu, Kana
AU - Bullman, Susan
AU - Garrett, Wendy S.
AU - Huttenhower, Curtis
AU - Meyerhardt, Jeffrey A.
AU - Giannakis, Marios
AU - Chan, Andrew T.
AU - Fuchs, Charles S.
AU - Ogino, Shuji
N1 - Publisher Copyright:
© 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
PY - 2020/4/1
Y1 - 2020/4/1
N2 - 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.
AB - 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.
KW - Colorectal neoplasms
KW - Immunology
KW - Microbiology
KW - Microbiome
KW - Molecular pathological epidemiology
KW - Tumour microenvironment
UR - https://www.scopus.com/pages/publications/85078933979
UR - https://www.scopus.com/pages/publications/85078933979#tab=citedBy
U2 - 10.1002/path.5381
DO - 10.1002/path.5381
M3 - Article
C2 - 31880318
AN - SCOPUS:85078933979
SN - 0022-3417
VL - 250
SP - 397
EP - 408
JO - Journal of Pathology
JF - Journal of Pathology
IS - 4
ER -
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