子宫内膜癌分子亚型的种族差异。
Racial disparities in molecular subtypes of endometrial cancer.
机构信息
Gynecologic Cancer Center of Excellence, Department of Obstetrics & Gynecology, Walter Reed National Military Medical Center, Uniformed Services University of the Health Sciences, 8901 Wisconsin Avenue, Bethesda, MD 20889, United States; Gynecologic Oncology Division, Department of Obstetrics and Gynecology, Naval Medical Center Portsmouth, 620 John Paul Jones Cir, Portsmouth, VA 23708, United States.
Gynecologic Cancer Center of Excellence, Department of Obstetrics & Gynecology, Walter Reed National Military Medical Center, Uniformed Services University of the Health Sciences, 8901 Wisconsin Avenue, Bethesda, MD 20889, United States.
出版信息
Gynecol Oncol. 2018 Apr;149(1):106-116. doi: 10.1016/j.ygyno.2017.12.009.
OBJECTIVES
Racial differences in the molecular subtypes of endometrial cancer and associations with progression-free survival (PFS) were evaluated.
METHODS
Molecular, clinical and PFS data were acquired from the Cancer Genome Atlas (TCGA) including classification into the integrative, somatic copy number alteration and transcript-based subtypes. The prevalence and prognostic value of the aggressive molecular subtypes (copy number variant [CNV]-high, cluster 4 or mitotic) were evaluated in Black and White patients.
RESULTS
There were 337 patients including 14% self-designated as Black, 27% with advanced stage, and 82% with endometrioid histology. The CNV-high subtype was more common in Black than White patients (61.9% vs. 23.5%, P=0.0005) and suggested worse PFS in Black patients (hazard ratio [HR]=3.4, P=0.189). The cluster 4 subtype was more prevalent in Black patients (56.8% vs. 20.9%, P<0.0001) and associated with worse PFS in Black patients (HR=3.4, P=0.049). The mitotic subtype was more abundant in Black patients (64.1% vs. 33.7%, P=0.002), indicated worse PFS in Black patients (HR=4.1, P=0.044) including the endometrioid histology (HR=6.1, P=0.024) and exhibited race-associated enrichment in cell cycle signaling and pathways in cancer including PLK1 and BIRC7. All of these aggressive molecular subtypes also indicated worse PFS in White patients, with unique enrichments in mitotic signaling different from Black patients.
CONCLUSIONS
The aggressive molecular subtypes from TCGA were more common in Black endometrial cancer patients and indicated worse PFS in both Black and White patients. The mitotic subtypes also indicated worse PFS in Black patients with endometrioid histology. Enrichment patterns in mitotic signaling may represent therapeutic opportunities.
目的
评估子宫内膜癌分子亚型的种族差异及其与无进展生存期（PFS）的关系。
方法
从癌症基因组图谱（TCGA）中获取分子、临床和 PFS 数据，包括整合、体细胞拷贝数改变和基于转录的亚型分类。评估黑人与白人患者中侵袭性分子亚型（拷贝数变异[CNV]-高、簇 4 或有丝分裂）的流行率和预后价值。
结果
共纳入 337 例患者，其中 14%自我认定为黑人，27%为晚期，82%为子宫内膜样组织学。CNV-高亚型在黑人患者中比白人患者更常见（61.9%比 23.5%，P=0.0005），并提示黑人患者的 PFS 较差（风险比[HR]=3.4，P=0.189）。簇 4 亚型在黑人患者中更为普遍（56.8%比 20.9%，P<0.0001），并与黑人患者的 PFS 较差相关（HR=3.4，P=0.049）。有丝分裂亚型在黑人患者中更为丰富（64.1%比 33.7%，P=0.002），提示黑人患者的 PFS 较差（HR=4.1，P=0.044），包括子宫内膜样组织学（HR=6.1，P=0.024），并在细胞周期信号和癌症途径中表现出与种族相关的富集，包括 PLK1 和 BIRC7。所有这些侵袭性分子亚型在白人患者中也提示 PFS 较差，与黑人患者不同，有丝分裂信号的独特富集。
结论
TCGA 的侵袭性分子亚型在黑人子宫内膜癌患者中更为常见，并提示黑人与白人患者的 PFS 均较差。有丝分裂亚型也提示黑人患者的子宫内膜样组织学 PFS 较差。有丝分裂信号的富集模式可能代表治疗机会。
Zotero 插件