TY - JOUR
T1 - The Amount of Bifidobacterium Genus in Colorectal Carcinoma Tissue in Relation to Tumor Characteristics and Clinical Outcome
AU - Kosumi, Keisuke
AU - Hamada, Tsuyoshi
AU - Koh, Hideo
AU - Borowsky, Jennifer
AU - Bullman, Susan
AU - Twombly, Tyler S.
AU - Nevo, Daniel
AU - Masugi, Yohei
AU - Liu, Li
AU - da Silva, Annacarolina
AU - Chen, Yang
AU - Du, Chunxia
AU - Gu, Mancang
AU - Li, Chenxi
AU - Li, Wanwan
AU - Liu, Hongli
AU - Shi, Yan
AU - Mima, Kosuke
AU - Song, Mingyang
AU - Nosho, Katsuhiko
AU - Nowak, Jonathan A.
AU - Nishihara, Reiko
AU - Baba, Hideo
AU - Zhang, Xuehong
AU - Wu, Kana
AU - Wang, Molin
AU - Huttenhower, Curtis
AU - Garrett, Wendy S.
AU - Meyerson, Matthew L.
AU - Lennerz, Jochen K.
AU - Giannakis, Marios
AU - Chan, Andrew T.
AU - Meyerhardt, Jeffrey A.
AU - Fuchs, Charles S.
AU - Ogino, Shuji
N1 - Funding Information:
Supported by US NIH grants P01 CA87969 (M.S.), UM1 CA186107, P01 CA55075, UM1 CA167552, U01 CA167552, P50 CA127003 (C.S.F.), R01 CA118553 (C.S.F.), R01 CA169141 (C.S.F.), R01 CA137178 (A.T.C.), K24 DK098311 (A.T.C.), R35 CA197735 (S.O.), R01 CA151993 (S.O.), K07 CA190673 (R.N.), and K07 CA188126 (X.Z.), the Dana-Farber/Harvard Cancer Center Nodal Award (S.O.), Stand Up to Cancer Colorectal Cancer Dream Team Translational Research grant (C.S.F. and M.Gi.), the Project P Fund grant, The Friends of the Dana-Farber Cancer Institute grant, the Bennett Family Fund grant, the Entertainment Industry Foundation through the National Colorectal Cancer Research Alliance grant, Japan Society for the Promotion of Science Overseas Research Fellowship grant JP2017-775 (K.K.), the Mitsukoshi Health and Welfare Foundation (T.H.), the Australia Awards-Endeavour Scholarships and Fellowships Program (J.B.), and China Scholarship Council and a Huazhong University of Science and Technology fellowship grant (L.L.). A.T.C. is a Stuart and Suzanne Steele Massachusetts General Hospital Research Scholar.
Publisher Copyright:
© 2018 American Society for Investigative Pathology
PY - 2018/12
Y1 - 2018/12
N2 - Evidence indicates a complex link between microbiota, tumor characteristics, and host immunity in the tumor microenvironment. In experimental studies, bifidobacteria appear to modulate intestinal epithelial cell differentiation. Accumulating evidence suggests that bifidobacteria may enhance the antitumor immunity and efficacy of immunotherapy. We hypothesized that the amount of bifidobacteria in colorectal carcinoma tissue might be associated with tumor differentiation and higher immune response to colorectal cancer. Using a molecular pathologic epidemiology database of 1313 rectal and colon cancers, we measured the amount of Bifidobacterium DNA in carcinoma tissue by a quantitative PCR assay. The multivariable regression model was used to adjust for potential confounders, including microsatellite instability status, CpG island methylator phenotype, long-interspersed nucleotide element-1 methylation, and KRAS, BRAF, and PIK3CA mutations. Intratumor bifidobacteria were detected in 393 cases (30%). The amount of bifidobacteria was associated with the extent of signet ring cells (P = 0.002). Compared with Bifidobacterium-negative cases, multivariable odd ratios for the extent of signet ring cells were 1.29 (95% CI, 0.74–2.24) for Bifidobacterium-low cases and 1.87 (95% CI, 1.16–3.02) for Bifidobacterium-high cases (Ptrend = 0.01). The association between intratumor bifidobacteria and signet ring cells suggests a possible role of bifidobacteria in determining distinct tumor characteristics or as an indicator of dysfunctional mucosal barrier in colorectal cancer.
AB - Evidence indicates a complex link between microbiota, tumor characteristics, and host immunity in the tumor microenvironment. In experimental studies, bifidobacteria appear to modulate intestinal epithelial cell differentiation. Accumulating evidence suggests that bifidobacteria may enhance the antitumor immunity and efficacy of immunotherapy. We hypothesized that the amount of bifidobacteria in colorectal carcinoma tissue might be associated with tumor differentiation and higher immune response to colorectal cancer. Using a molecular pathologic epidemiology database of 1313 rectal and colon cancers, we measured the amount of Bifidobacterium DNA in carcinoma tissue by a quantitative PCR assay. The multivariable regression model was used to adjust for potential confounders, including microsatellite instability status, CpG island methylator phenotype, long-interspersed nucleotide element-1 methylation, and KRAS, BRAF, and PIK3CA mutations. Intratumor bifidobacteria were detected in 393 cases (30%). The amount of bifidobacteria was associated with the extent of signet ring cells (P = 0.002). Compared with Bifidobacterium-negative cases, multivariable odd ratios for the extent of signet ring cells were 1.29 (95% CI, 0.74–2.24) for Bifidobacterium-low cases and 1.87 (95% CI, 1.16–3.02) for Bifidobacterium-high cases (Ptrend = 0.01). The association between intratumor bifidobacteria and signet ring cells suggests a possible role of bifidobacteria in determining distinct tumor characteristics or as an indicator of dysfunctional mucosal barrier in colorectal cancer.
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U2 - 10.1016/j.ajpath.2018.08.015
DO - 10.1016/j.ajpath.2018.08.015
M3 - Article
C2 - 30243655
AN - SCOPUS:85056764487
SN - 0002-9440
VL - 188
SP - 2839
EP - 2852
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 12
ER -
