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Race‐specific molecular alterations correlate with differential outcomes for black and white endometrioid endometrial cancer patients
Author(s) -
Bateman Nicholas W.,
Dubil Elizabeth A.,
Wang Guisong,
Hood Brian L.,
Oliver Julie M.,
Litzi Tracy A.,
Gist Glenn D.,
Mitchell David A.,
Blanton Brian,
Phippen Neil T.,
Tian Chunqiao,
Zahn Christopher M.,
Cohn David E.,
Havrilesky Laura J.,
Berchuck Andrew,
Shriver Craig D.,
Darcy Kathleen M.,
Hamilton Chad A.,
Conrads Thomas P.,
Maxwell G. Larry
Publication year - 2017
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.30813
Subject(s) - hazard ratio , proportional hazards model , endometrial cancer , medicine , oncology , ovarian cancer , univariate analysis , cancer , multivariate analysis , andrology , biology , confidence interval
BACKGROUND The objective of this study was to identify molecular alterations associated with disease outcomes for white and black patients with endometrioid endometrial cancer (EEC). METHODS EEC samples from black (n = 17) and white patients (n = 13) were analyzed by proteomics (liquid chromatography–tandem mass spectrometry) and transcriptomics (RNA‐seq). Coordinate alterations were validated with RNA‐seq data from black (n = 49) and white patients (n = 216). Concordantly altered candidates were further tested for associations with race‐specific progression‐free survival (PFS) in black (n = 64) or white patients (n = 267) via univariate and multivariate Cox regression modeling and log‐rank testing. RESULTS Discovery analyses revealed significantly altered candidate proteins and transcripts between black and white patients, suggesting modulation of tumor cell viability in black patients and cell death signaling in black and white patients. Eighty‐nine candidates were validated as altered between these patient cohorts, and a subset significantly correlated with differential PFS. White‐specific PFS candidates included serpin family A member 4 (SERPINA4; hazard ratio [HR], 0.89; Wald P value = .02), integrin subunit α3 (ITGA3; HR, 0.76; P = .03), and Bet1 Golgi vesicular membrane trafficking protein like (BET1L; HR, 0.48; P = .04). Black‐specific PFS candidates included family with sequence similarity 228 member B (FAM228B; HR, 0.13; P = .001) and HEAT repeat containing 6 (HEATR6; HR, 4.94; P = .047). Several candidates were also associated with overall survival (SERPINA4 and ITGA3) as well as PFS independent of disease stage, grade and myometrial invasion (SERPINA4, BET1L and FAM228B). CONCLUSIONS This study has identified and validated molecular alterations in tumors from black and white EEC patients, including candidates significantly associated with altered disease outcomes within these patient cohorts. Cancer 2017;123:4004‐12 . © 2017 American Cancer Society .