Race-Specific Molecular Alterations Correlate With Differential Outcomes for Black and White Endometrioid Endometrial Cancer Patients
Race-Specific Molecular Alterations Correlate With Differential Outcomes for Black and White Endometrioid Endometrial Cancer Patients
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DOI：
10.1002/cncr.30813
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发表时间：
2017-10-15
期刊：
影响因子：
6.2
通讯作者：
Maxwell, G. Larry
中科院分区：
文献类型：
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作者：
Bateman, Nicholas W.;Dubil, Elizabeth A.;Maxwell, G. Larry
背景：本研究的目的是确定与白人和黑人子宫内膜样子宫内膜癌（EEC）患者疾病结局相关的分子改变。方法：采用蛋白质组学（液相色谱-串联质谱）和转录组学（RNA-seq）对黑人（17例）和白人（13例）的脑电图样本进行分析。用来自黑人（n = 49）和白人（n = 216）患者的RNA-seq数据验证坐标改变。通过单变量和多变量Cox回归模型和log-rank检验，进一步测试了黑人（n = 64）或白人（n = 267）患者中一致性改变的候选人与种族特异性无进展生存期（PFS）的关联。结果：发现分析显示，黑人和白人患者之间的候选蛋白和转录本显著改变，表明黑人患者的肿瘤细胞活力和黑人和白人患者的细胞死亡信号的调节。89名候选患者在这些患者队列之间被验证为改变，其中一个子集与差异PFS显着相关。白色特异性PFS候选者包括serpin家族A成员4 （SERPINA4；风险比[HR]， 0.89； Wald P值= 0.02）、整合素亚单位α 3 （ITGA3；风险比，0.76;P = 0.03）和Bet1高尔基囊泡膜运输蛋白样（BET1L；风险比，0.48;P = 0.04）。黑人特异性PFS候选者包括序列相似性为228成员B的家族（FAM228B； HR, 0.13; P = .001）和包含6个成员的HEAT重复序列（heat6； HR, 4.94; P = .047）。一些候选药物也与总生存期（SERPINA4和ITGA3）以及独立于疾病分期、分级和子宫内膜浸润（SERPINA4、BET1L和FAM228B）的PFS相关。结论：这项研究已经确定并验证了黑人和白人脑电图患者肿瘤中的分子改变，包括这些患者队列中与疾病结局改变显著相关的候选患者。12. (C) 2017美国癌症协会。
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 alpha 3 (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. 12. (C) 2017 American Cancer Society.