Prognostic association of PTGS2 (COX-2) over-expression according to BRAF mutation status in colorectal cancer: Results from two prospective cohorts and CALGB 89803 (Alliance) trial

Keisuke Kosumi; Tsuyoshi Hamada; Sui Zhang; Li Liu; Annacarolina da Silva; Hideo Koh; Tyler S. Twombly; Kosuke Mima; Teppei Morikawa; Mingyang Song; Jonathan A. Nowak; Reiko Nishihara; Leonard B. Saltz; Donna Niedzwiecki; Fang Shu Ou; Tyler Zemla; Robert J. Mayer; Hideo Baba; Kimmie Ng; Marios Giannakis; Xuehong Zhang; Kana Wu; Edward L. Giovannucci; Andrew T. Chan; Charles S. Fuchs; Jeffrey A. Meyerhardt; Shuji Ogino

doi:10.1016/j.ejca.2019.01.022

Prognostic association of PTGS2 (COX-2) over-expression according to BRAF mutation status in colorectal cancer: Results from two prospective cohorts and CALGB 89803 (Alliance) trial

Keisuke Kosumi, Tsuyoshi Hamada, Sui Zhang, Li Liu, Annacarolina da Silva, Hideo Koh, Tyler S. Twombly, Kosuke Mima, Teppei Morikawa, Mingyang Song, Jonathan A. Nowak, Reiko Nishihara, Leonard B. Saltz, Donna Niedzwiecki, Fang Shu Ou, Tyler Zemla, Robert J. Mayer, Hideo Baba, Kimmie Ng, Marios GiannakisXuehong Zhang, Kana Wu, Edward L. Giovannucci, Andrew T. Chan, Charles S. Fuchs, Jeffrey A. Meyerhardt, Shuji Ogino

Health Sciences Research

Research output: Contribution to journal › Article

5 Scopus citations

Abstract

Background: Prostaglandin-endoperoxide synthase 2 (PTGS2, cyclooxygenase-2, COX-2)-prostaglandin E ₂ (PGE ₂ ) pathway promotes tumour progression. Considering evidence suggesting increased PGE ₂ synthesis by BRAF mutation in tumour cells, we hypothesised that the association of tumour PTGS2 (COX-2) expression with colorectal cancer mortality might be stronger in BRAF-mutated tumours than in BRAF-wild-type tumours. Methods: Using 1708 patients, including 1200 stage I-IV colorectal carcinoma cases in the Nurses’ Health Study (NHS) and the Health Professionals Follow-up Study (HPFS) and 508 stage III colon cancer cases in a National Cancer Institute–sponsored randomised controlled trial of adjuvant therapy (CALGB/Alliance 89803), we evaluated tumour PTGS2 (COX-2) expression status using immunohistochemistry. We examined the prognostic association of PTGS2 (COX-2) expression in strata of BRAF mutation status by multivariable Cox proportional hazards regression models to adjust for potential confounders, including disease stage, tumour differentiation, microsatellite instability status and KRAS and PIK3CA mutations. Results: In NHS and HPFS, the association of PTGS2 (COX-2) expression with colorectal cancer-specific survival differed by BRAF mutation status (P _interaction = 0.0005); compared with PTGS2 (COX-2)-negative/low carcinomas, the multivariable-adjusted hazard ratios for PTGS2 (COX-2)-high carcinomas were 2.44 (95% confidence interval, 1.39–4.28) in BRAF-mutated cases and 0.82 (95% confidence interval, 0.65–1.04) in BRAF-wild-type cases. Differential prognostic associations of PTGS2 (COX-2) expression in strata of BRAF mutation status were similarly observed in CALGB/Alliance 89803 trial (P _interaction = 0.03). Conclusions: The association of tumour PTGS2 (COX-2) expression with colorectal cancer mortality is stronger in BRAF-mutated tumours than in BRAF-wild-type tumours, supporting interactive roles of PTGS2 (COX-2) expression and BRAF mutation statuses in prognostication of patients with colorectal cancer; ClinicalTrials.gov Identifier, NCT00003835.

Original language	English (US)
Pages (from-to)	82-93
Number of pages	12
Journal	European Journal of Cancer
Volume	111
DOIs	https://doi.org/10.1016/j.ejca.2019.01.022
State	Published - Apr 2019

Keywords

Adenocarcinoma
Clinical outcome
Colorectal neoplasm
Immunity
Inflammation
Molecular pathological epidemiology
PTGS
Precision medicine
Prostaglandin
RAF

ASJC Scopus subject areas

Oncology
Cancer Research

Access to Document

10.1016/j.ejca.2019.01.022

Fingerprint Dive into the research topics of 'Prognostic association of PTGS2 (COX-2) over-expression according to BRAF mutation status in colorectal cancer: Results from two prospective cohorts and CALGB 89803 (Alliance) trial'. Together they form a unique fingerprint.

Cite this

Kosumi, K., Hamada, T., Zhang, S., Liu, L., da Silva, A., Koh, H., Twombly, T. S., Mima, K., Morikawa, T., Song, M., Nowak, J. A., Nishihara, R., Saltz, L. B., Niedzwiecki, D., Ou, F. S., Zemla, T., Mayer, R. J., Baba, H., Ng, K., ... Ogino, S. (2019). Prognostic association of PTGS2 (COX-2) over-expression according to BRAF mutation status in colorectal cancer: Results from two prospective cohorts and CALGB 89803 (Alliance) trial. European Journal of Cancer, 111, 82-93. https://doi.org/10.1016/j.ejca.2019.01.022

Prognostic association of PTGS2 (COX-2) over-expression according to BRAF mutation status in colorectal cancer : Results from two prospective cohorts and CALGB 89803 (Alliance) trial. / Kosumi, Keisuke; Hamada, Tsuyoshi; Zhang, Sui; Liu, Li; da Silva, Annacarolina; Koh, Hideo; Twombly, Tyler S.; Mima, Kosuke; Morikawa, Teppei; Song, Mingyang; Nowak, Jonathan A.; Nishihara, Reiko; Saltz, Leonard B.; Niedzwiecki, Donna; Ou, Fang Shu; Zemla, Tyler; Mayer, Robert J.; Baba, Hideo; Ng, Kimmie; Giannakis, Marios; Zhang, Xuehong; Wu, Kana; Giovannucci, Edward L.; Chan, Andrew T.; Fuchs, Charles S.; Meyerhardt, Jeffrey A.; Ogino, Shuji.

In: European Journal of Cancer, Vol. 111, 04.2019, p. 82-93.

Research output: Contribution to journal › Article

Kosumi, K, Hamada, T, Zhang, S, Liu, L, da Silva, A, Koh, H, Twombly, TS, Mima, K, Morikawa, T, Song, M, Nowak, JA, Nishihara, R, Saltz, LB, Niedzwiecki, D, Ou, FS, Zemla, T, Mayer, RJ, Baba, H, Ng, K, Giannakis, M, Zhang, X, Wu, K, Giovannucci, EL, Chan, AT, Fuchs, CS, Meyerhardt, JA & Ogino, S 2019, 'Prognostic association of PTGS2 (COX-2) over-expression according to BRAF mutation status in colorectal cancer: Results from two prospective cohorts and CALGB 89803 (Alliance) trial', European Journal of Cancer, vol. 111, pp. 82-93. https://doi.org/10.1016/j.ejca.2019.01.022

Kosumi, Keisuke ; Hamada, Tsuyoshi ; Zhang, Sui ; Liu, Li ; da Silva, Annacarolina ; Koh, Hideo ; Twombly, Tyler S. ; Mima, Kosuke ; Morikawa, Teppei ; Song, Mingyang ; Nowak, Jonathan A. ; Nishihara, Reiko ; Saltz, Leonard B. ; Niedzwiecki, Donna ; Ou, Fang Shu ; Zemla, Tyler ; Mayer, Robert J. ; Baba, Hideo ; Ng, Kimmie ; Giannakis, Marios ; Zhang, Xuehong ; Wu, Kana ; Giovannucci, Edward L. ; Chan, Andrew T. ; Fuchs, Charles S. ; Meyerhardt, Jeffrey A. ; Ogino, Shuji. / Prognostic association of PTGS2 (COX-2) over-expression according to BRAF mutation status in colorectal cancer : Results from two prospective cohorts and CALGB 89803 (Alliance) trial. In: European Journal of Cancer. 2019 ; Vol. 111. pp. 82-93.

@article{c617b7fed72742f59bb9367c80e00e02,

title = "Prognostic association of PTGS2 (COX-2) over-expression according to BRAF mutation status in colorectal cancer: Results from two prospective cohorts and CALGB 89803 (Alliance) trial",

abstract = " Background: Prostaglandin-endoperoxide synthase 2 (PTGS2, cyclooxygenase-2, COX-2)-prostaglandin E 2 (PGE 2 ) pathway promotes tumour progression. Considering evidence suggesting increased PGE 2 synthesis by BRAF mutation in tumour cells, we hypothesised that the association of tumour PTGS2 (COX-2) expression with colorectal cancer mortality might be stronger in BRAF-mutated tumours than in BRAF-wild-type tumours. Methods: Using 1708 patients, including 1200 stage I-IV colorectal carcinoma cases in the Nurses{\textquoteright} Health Study (NHS) and the Health Professionals Follow-up Study (HPFS) and 508 stage III colon cancer cases in a National Cancer Institute–sponsored randomised controlled trial of adjuvant therapy (CALGB/Alliance 89803), we evaluated tumour PTGS2 (COX-2) expression status using immunohistochemistry. We examined the prognostic association of PTGS2 (COX-2) expression in strata of BRAF mutation status by multivariable Cox proportional hazards regression models to adjust for potential confounders, including disease stage, tumour differentiation, microsatellite instability status and KRAS and PIK3CA mutations. Results: In NHS and HPFS, the association of PTGS2 (COX-2) expression with colorectal cancer-specific survival differed by BRAF mutation status (P interaction = 0.0005); compared with PTGS2 (COX-2)-negative/low carcinomas, the multivariable-adjusted hazard ratios for PTGS2 (COX-2)-high carcinomas were 2.44 (95% confidence interval, 1.39–4.28) in BRAF-mutated cases and 0.82 (95% confidence interval, 0.65–1.04) in BRAF-wild-type cases. Differential prognostic associations of PTGS2 (COX-2) expression in strata of BRAF mutation status were similarly observed in CALGB/Alliance 89803 trial (P interaction = 0.03). Conclusions: The association of tumour PTGS2 (COX-2) expression with colorectal cancer mortality is stronger in BRAF-mutated tumours than in BRAF-wild-type tumours, supporting interactive roles of PTGS2 (COX-2) expression and BRAF mutation statuses in prognostication of patients with colorectal cancer; ClinicalTrials.gov Identifier, NCT00003835. ",

keywords = "Adenocarcinoma, Clinical outcome, Colorectal neoplasm, Immunity, Inflammation, Molecular pathological epidemiology, PTGS, Precision medicine, Prostaglandin, RAF",

author = "Keisuke Kosumi and Tsuyoshi Hamada and Sui Zhang and Li Liu and {da Silva}, Annacarolina and Hideo Koh and Twombly, {Tyler S.} and Kosuke Mima and Teppei Morikawa and Mingyang Song and Nowak, {Jonathan A.} and Reiko Nishihara and Saltz, {Leonard B.} and Donna Niedzwiecki and Ou, {Fang Shu} and Tyler Zemla and Mayer, {Robert J.} and Hideo Baba and Kimmie Ng and Marios Giannakis and Xuehong Zhang and Kana Wu and Giovannucci, {Edward L.} and Chan, {Andrew T.} and Fuchs, {Charles S.} and Meyerhardt, {Jeffrey A.} and Shuji Ogino",

year = "2019",

month = apr,

doi = "10.1016/j.ejca.2019.01.022",

language = "English (US)",

volume = "111",

pages = "82--93",

journal = "European Journal of Cancer",

issn = "0959-8049",

publisher = "Elsevier Limited",

}

TY - JOUR

T1 - Prognostic association of PTGS2 (COX-2) over-expression according to BRAF mutation status in colorectal cancer

T2 - Results from two prospective cohorts and CALGB 89803 (Alliance) trial

AU - Kosumi, Keisuke

AU - Hamada, Tsuyoshi

AU - Zhang, Sui

AU - Liu, Li

AU - da Silva, Annacarolina

AU - Koh, Hideo

AU - Twombly, Tyler S.

AU - Mima, Kosuke

AU - Morikawa, Teppei

AU - Song, Mingyang

AU - Nowak, Jonathan A.

AU - Nishihara, Reiko

AU - Saltz, Leonard B.

AU - Niedzwiecki, Donna

AU - Ou, Fang Shu

AU - Zemla, Tyler

AU - Mayer, Robert J.

AU - Baba, Hideo

AU - Ng, Kimmie

AU - Giannakis, Marios

AU - Zhang, Xuehong

AU - Wu, Kana

AU - Giovannucci, Edward L.

AU - Chan, Andrew T.

AU - Fuchs, Charles S.

AU - Meyerhardt, Jeffrey A.

AU - Ogino, Shuji

PY - 2019/4

Y1 - 2019/4

N2 - Background: Prostaglandin-endoperoxide synthase 2 (PTGS2, cyclooxygenase-2, COX-2)-prostaglandin E 2 (PGE 2 ) pathway promotes tumour progression. Considering evidence suggesting increased PGE 2 synthesis by BRAF mutation in tumour cells, we hypothesised that the association of tumour PTGS2 (COX-2) expression with colorectal cancer mortality might be stronger in BRAF-mutated tumours than in BRAF-wild-type tumours. Methods: Using 1708 patients, including 1200 stage I-IV colorectal carcinoma cases in the Nurses’ Health Study (NHS) and the Health Professionals Follow-up Study (HPFS) and 508 stage III colon cancer cases in a National Cancer Institute–sponsored randomised controlled trial of adjuvant therapy (CALGB/Alliance 89803), we evaluated tumour PTGS2 (COX-2) expression status using immunohistochemistry. We examined the prognostic association of PTGS2 (COX-2) expression in strata of BRAF mutation status by multivariable Cox proportional hazards regression models to adjust for potential confounders, including disease stage, tumour differentiation, microsatellite instability status and KRAS and PIK3CA mutations. Results: In NHS and HPFS, the association of PTGS2 (COX-2) expression with colorectal cancer-specific survival differed by BRAF mutation status (P interaction = 0.0005); compared with PTGS2 (COX-2)-negative/low carcinomas, the multivariable-adjusted hazard ratios for PTGS2 (COX-2)-high carcinomas were 2.44 (95% confidence interval, 1.39–4.28) in BRAF-mutated cases and 0.82 (95% confidence interval, 0.65–1.04) in BRAF-wild-type cases. Differential prognostic associations of PTGS2 (COX-2) expression in strata of BRAF mutation status were similarly observed in CALGB/Alliance 89803 trial (P interaction = 0.03). Conclusions: The association of tumour PTGS2 (COX-2) expression with colorectal cancer mortality is stronger in BRAF-mutated tumours than in BRAF-wild-type tumours, supporting interactive roles of PTGS2 (COX-2) expression and BRAF mutation statuses in prognostication of patients with colorectal cancer; ClinicalTrials.gov Identifier, NCT00003835.

AB - Background: Prostaglandin-endoperoxide synthase 2 (PTGS2, cyclooxygenase-2, COX-2)-prostaglandin E 2 (PGE 2 ) pathway promotes tumour progression. Considering evidence suggesting increased PGE 2 synthesis by BRAF mutation in tumour cells, we hypothesised that the association of tumour PTGS2 (COX-2) expression with colorectal cancer mortality might be stronger in BRAF-mutated tumours than in BRAF-wild-type tumours. Methods: Using 1708 patients, including 1200 stage I-IV colorectal carcinoma cases in the Nurses’ Health Study (NHS) and the Health Professionals Follow-up Study (HPFS) and 508 stage III colon cancer cases in a National Cancer Institute–sponsored randomised controlled trial of adjuvant therapy (CALGB/Alliance 89803), we evaluated tumour PTGS2 (COX-2) expression status using immunohistochemistry. We examined the prognostic association of PTGS2 (COX-2) expression in strata of BRAF mutation status by multivariable Cox proportional hazards regression models to adjust for potential confounders, including disease stage, tumour differentiation, microsatellite instability status and KRAS and PIK3CA mutations. Results: In NHS and HPFS, the association of PTGS2 (COX-2) expression with colorectal cancer-specific survival differed by BRAF mutation status (P interaction = 0.0005); compared with PTGS2 (COX-2)-negative/low carcinomas, the multivariable-adjusted hazard ratios for PTGS2 (COX-2)-high carcinomas were 2.44 (95% confidence interval, 1.39–4.28) in BRAF-mutated cases and 0.82 (95% confidence interval, 0.65–1.04) in BRAF-wild-type cases. Differential prognostic associations of PTGS2 (COX-2) expression in strata of BRAF mutation status were similarly observed in CALGB/Alliance 89803 trial (P interaction = 0.03). Conclusions: The association of tumour PTGS2 (COX-2) expression with colorectal cancer mortality is stronger in BRAF-mutated tumours than in BRAF-wild-type tumours, supporting interactive roles of PTGS2 (COX-2) expression and BRAF mutation statuses in prognostication of patients with colorectal cancer; ClinicalTrials.gov Identifier, NCT00003835.

KW - Adenocarcinoma

KW - Clinical outcome

KW - Colorectal neoplasm

KW - Immunity

KW - Inflammation

KW - Molecular pathological epidemiology

KW - PTGS

KW - Precision medicine

KW - Prostaglandin

KW - RAF

UR - http://www.scopus.com/inward/record.url?scp=85062156576&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85062156576&partnerID=8YFLogxK

U2 - 10.1016/j.ejca.2019.01.022

DO - 10.1016/j.ejca.2019.01.022

M3 - Article

C2 - 30826660

AN - SCOPUS:85062156576

VL - 111

SP - 82

EP - 93

JO - European Journal of Cancer

JF - European Journal of Cancer

SN - 0959-8049

ER -