University of Oulu

Haruki, K., Kosumi, K., Hamada, T., Twombly, T.S., Väyrynen, J.P., Kim, S.A., Masugi, Y., Qian, Z.R., Mima, K., Baba, Y., da Silva, A., Borowsky, J., Arima, K., Fujiyoshi, K., Lau, M.C., Li, P., Guo, C., Chen, Y., Song, M., Nowak, J.A., Nishihara, R., Yanaga, K., Zhang, X., Wu, K., Bullman, S., Garrett, W.S., Huttenhower, C., Meyerhardt, J.A., Giannakis, M., Chan, A.T., Fuchs, C.S. and Ogino, S. (2020), Association of autophagy status with amount of Fusobacterium nucleatum in colorectal cancer. J. Pathol., 250: 397-408. doi:10.1002/path.5381

Association of autophagy status with amount of Fusobacterium nucleatum in colorectal cancer

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Author: Haruki, Koichiro1,2,3; Kosumi, Keisuke1,2; Hamada, Tsuyoshi1,2;
Organizations: 1Brigham & Womens Hosp, Dept Pathol, Program MPE Mol Pathol Epidemiol, 221 Longwood Ave,EBRC Room 404A, Boston, MA 02115 USA.
2Harvard Med Sch, Boston, MA 02115 USA.
3Jikei Univ, Sch Med, Dept Surg, Tokyo, Japan.
4Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
5Univ Oulu, Oulu Univ Hosp, Med Res Ctr Oulu, Canc & Translat Med Res Unit, Oulu, Finland.
6Sun Yat Sen Univ, Affiliated Hosp 7, Sci Res Ctr, Shenzhen, Peoples R China.
7Sun Yat Sen Univ, Affiliated Hosp 7, Digest Dis Ctr, Shenzhen, Peoples R China.
8Massachusetts Gen Hosp, Dept Pathol, Ctr Integrated Diagnost, Boston, MA 02114 USA.
9Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA.
10Massachusetts Gen Hosp, Clin & Translat Epidemiol Unit, Boston, MA 02114 USA.
11Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA.
12Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
13Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA USA.
14Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA.
15Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
16Harvard TH Chan Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA USA.
17Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
18Yale Canc Ctr, New Haven, CT USA.
19Yale Sch Med, Dept Med, New Haven, CT USA.
20Smilow Canc Hosp, New Haven, CT USA.
21Dana Farber Harvard Canc Ctr, Canc Immunol Program, Boston, MA USA.
22Dana Farber Harvard Canc Ctr, Canc Epidemiol Program, Boston, MA USA.
Format: article
Version: accepted version
Access: embargoed
Persistent link: http://urn.fi/urn:nbn:fi-fe2020060240206
Language: English
Published: John Wiley & Sons, 2020
Publish Date: 2020-12-27
Description:

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.

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Series: Journal of pathology
ISSN: 0022-3417
ISSN-E: 1096-9896
ISSN-L: 0022-3417
Volume: 250
Issue: 4
DOI: 10.1002/path.5381
OADOI: https://oadoi.org/10.1002/path.5381
Type of Publication: A1 Journal article – refereed
Field of Science: 3122 Cancers
Subjects:
Funding: This work was supported by US National Institutes of Health (NIH) grants (P01 CA87969 to MJ Stampfer; UM1 CA186107 to MJ Stampfer; P01 CA55075 to WC Willett; UM1 CA167552 to WC Willett; U01 CA167552 to WC Willett and LA Mucci; P50 CA127003 to CSF; R01 CA118553 to CSF; R01 CA169141 to CSF; R01 CA137178 to ATC; K24 DK098311 to ATC; R35 CA197735 to SO; R01 CA151993 to SO; K07 CA190673 to RN; and K07 CA188126 to XZ); by Cancer Research UK’s Grand Challenge Initiative (C10674/A27140 to WSG, MG, CH, and SO); by Nodal Award (2016-02) from the Dana-Farber Harvard Cancer Center (to SO); by the Stand Up to Cancer Colorectal Cancer Dream Team Translational Research Grant (SU2C-AACR-DT22-17 to CSF. and MG), administered by the American Association for Cancer Research, a scientific partner of SU2C; and by grants from the Project P Fund, The Friends of the Dana-Farber Cancer Institute, Bennett Family Fund, and the Entertainment Industry Foundation through National Colorectal Cancer Research Alliance and SU2C. KH was supported by fellowship grants from the Uehara Memorial Foundation and the Mitsukoshi Health and Welfare Foundation. KK was supported by grants from Overseas Research Fellowship (JP2017-0775) from Japan Society for the Promotion of Science and JSPS Fujita Memorial Fund for Medical Research. KA was supported by a grant from Overseas Research Fellowship (JP2018-60083) from Japan Society for the Promotion of Science. JB was supported by a grant from the Australia Awards-Endeavour Scholarships and Fellowships Program. KF was supported by a fellowship grant from the Uehara Memorial Foundation. MG is supported by an ASCO Conquer Cancer Foundation Career Development Award. ATC is a Stuart and Suzanne Steele MGH Research Scholar. The content is solely the responsibility of the authors and does not necessarily represent the official views of NIH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Copyright information: © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. This is the peer reviewed version of the following article: Haruki, K., Kosumi, K., Hamada, T., Twombly, T.S., Väyrynen, J.P., Kim, S.A., Masugi, Y., Qian, Z.R., Mima, K., Baba, Y., da Silva, A., Borowsky, J., Arima, K., Fujiyoshi, K., Lau, M.C., Li, P., Guo, C., Chen, Y., Song, M., Nowak, J.A., Nishihara, R., Yanaga, K., Zhang, X., Wu, K., Bullman, S., Garrett, W.S., Huttenhower, C., Meyerhardt, J.A., Giannakis, M., Chan, A.T., Fuchs, C.S. and Ogino, S. (2020), Association of autophagy status with amount of Fusobacterium nucleatum in colorectal cancer. J. Pathol., 250: 397-408, which has been published in final form at https://doi.org/10.1002/path.5381. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving."