University of Oulu

Haruki, K., Kosumi, K., Li, P. et al. An integrated analysis of lymphocytic reaction, tumour molecular characteristics and patient survival in colorectal cancer. Br J Cancer 122, 1367–1377 (2020). https://doi.org/10.1038/s41416-020-0780-3

An integrated analysis of lymphocytic reaction, tumour molecular characteristics and patient survival in colorectal cancer

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Author: Haruki, Koichiro1; Kosumi, Keisuke1; Li, Peilong2;
Organizations: 1Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
2Department of Clinical Laboratory, The Second Hospital of Shandong University, Jinan, China
3Cancer and Translational Medicine Research Unit, Medical Research Center Oulu, Oulu University Hospital, and University of Oulu, Oulu, Finland
4Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MS, USA
5Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA
6Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
7Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
8Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, USA
9Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
10Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA
11Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
12Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA
13Yale Cancer Center, New Haven, CT, USA
14Department of Medicine, Yale School of Medicine, New Haven, CT, USA
15Smilow Cancer Hospital, New Haven, CT, USA
16Department of Epidemiology and Biostatistics, and the Ministry of Education Key Lab of Environment and Health, School of Public Health, Huazhong University of Science and Technology, Wuhan, China
17Broad Institute of MIT and Harvard, Cambridge, MA, USA
18Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
19Cancer Immunology and Cancer Epidemiology Programs, Dana-Farber Harvard Cancer Center, Boston, MA, USA
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 0.7 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe2021042712953
Language: English
Published: Springer Nature, 2020
Publish Date: 2021-04-27
Description:

Abstract

Background: Histological lymphocytic reaction is regarded as an independent prognostic marker in colorectal cancer. Considering the lack of adequate statistical power, adjustment for selection bias and comprehensive tumour molecular data in most previous studies, we investigated the strengths of the prognostic associations of lymphocytic reaction in colorectal carcinoma by utilising an integrative database of two prospective cohort studies.

Methods: We examined Crohn’s-like reaction, intratumoural periglandular reaction, peritumoural reaction and tumour-infiltrating lymphocytes in 1465 colorectal carcinoma cases. Using covariate data of 4420 colorectal cancer cases in total, inverse probability-weighted Cox proportional hazard regression model was used to control for selection bias (due to tissue availability) and potential confounders, including stage, MSI status, LINE-1 methylation, PTGS2 and CTNNB1 expression, KRAS, BRAF and PIK3CA mutations, and tumour neoantigen load.

Results: Higher levels of each lymphocytic reaction component were associated with better colorectal cancer-specific survival (Ptrend < 0.002). Compared with cases with negative/low intratumoural periglandular reaction, multivariable-adjusted HRs were 0.55 (95% CI, 0.42–0.71) in cases with intermediate reaction and 0.20 (95% CI, 0.12–0.35) in cases with high reaction. These relationships were consistent in strata of MSI status or neoantigen loads (Pinteraction > 0.2).

Conclusions: The four lymphocytic reaction components are prognostic biomarkers in colorectal carcinoma.

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Series: British journal of cancer
ISSN: 0007-0920
ISSN-E: 1532-1827
ISSN-L: 0007-0920
Volume: 122
Pages: 1367 - 1377
DOI: 10.1038/s41416-020-0780-3
OADOI: https://oadoi.org/10.1038/s41416-020-0780-3
Type of Publication: A1 Journal article – refereed
Field of Science: 3122 Cancers
Subjects:
Funding: This work was supported by U.S. National Institutes of Health (NIH) grants (P01 CA87969 to M.J. Stampfer; UM1 CA186107 to M.J. Stampfer; P01 CA55075 to W.C. Willett; UM1 CA167552 to W.C. Willett; U01 CA167552 to W.C. Willett and L.A. Mucci; P50 CA127003 to C.S.F.; R01 CA118553 to C.S.F.; R01 CA169141 to C.S.F.; R01 CA137178 to A.T.C.; K24 DK098311 to A.T.C.; R35 CA197735 to S.O.; R01 CA151993 to S.O.; K07 CA190673 to R.N.; K07 CA188126 to X.Z.); by Cancer Research UK’s Grand Challenge Initiative (C10674/A27140 to M.G. and S.O.); by Nodal Award (2016-02) from the Dana-Farber Harvard Cancer Center (to S.O.); by the Stand Up to Cancer Colorectal Cancer Dream Team Translational Research Grant (SU2C-AACR-DT22-17 to C.S.F. and M.G.), administered by the American Association for Cancer Research, a scientific partner of SU2C; 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. K.H. was supported by fellowship grants from the Uehara Memorial Foundation and the Mitsukoshi Health and Welfare Foundation. K.K. and K.A. were supported by grants from Overseas Research Fellowship from Japan Society for the Promotion of Science (JP2017-775 to K.K.; JP201860083 to K.A.). P.L. and Y.C. were supported by scholarship grants from Chinese Scholarship Council. M.G. was supported by a Conquer Cancer Foundation of ASCO Career Development Award. A.T.C. 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 the NIH.
Copyright information: © The Author(s), under exclusive licence to Cancer Research UK 2020. This work is published under the standard license to publish agreement. After 12 months the work will become freely available and the license terms will switch to a Creative Commons Attribution 4.0 International (CC BY 4.0).
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