Pearce Janina, Durr Caitlin, Qu Xufeng, Liu Jinze, Randall Leslie, Miller Devin, Sayeed Sadia, Bae-Jump Victoria, Sullivan Stephanie
Department of Obstetrics & Gynecology, Division of Gynecologic Oncology, Virginia Commonwealth University Health System, United States.
Department of Biostatistics, Virginia Commonwealth University Health System, United States.
Gynecol Oncol Rep. 2024 Mar 6;52:101360. doi: 10.1016/j.gore.2024.101360. eCollection 2024 Apr.
Endometrial cancer (EC) incidence and mortality are increasing with striking racial disparities. Race and obesity are known risk factors for EC, however, their relationship and impact on tumor biology in higher grade endometrioid EC are unclear. The objective of this pilot study was to identify gene- and pathway-level changes in tumors from Black patients compared to White, both in general and in the context of dichotomized BMI.
A single institution retrospective convenience sample was obtained for grade 2 or 3 endometrioid EC, equally distributed amongst Black and White patients. Tumor samples were analyzed with the Tempus Laboratories xT NGS-based genome profiling test. DESeq2 was applied to identify differentially expressed genes, and then subjected to ingenuity pathway analysis (IPA). Continuous variables were analyzed using unpaired t-tests, and categorical using Chi-squared and Fisher exact tests.
39 representative cases were identified and analyzed from 2006 to 2021. Baseline clinicopathologic characteristics were similar. 157 genes were differentially expressed in tumors from Black patients compared to White regardless of BMI. IPA identified 81 significantly different pathways between Black and White patients with a BMI < 40 kg/m, and 117 with a BMI ≥ 40 kg/m. Of these, eleven pathways were consistently and significantly activated or deactivated regardless of BMI.
Differences in gene expression and pathway activation in EC exist between race and BMI, which highlights the need for further research to better understand the implications of these differences on endometrioid EC progression, outcomes, and treatment in this historically underserved patient population.
子宫内膜癌（EC）的发病率和死亡率呈上升趋势，且存在显著的种族差异。种族和肥胖是已知的EC危险因素，然而，它们在高级别子宫内膜样EC中与肿瘤生物学的关系及影响尚不清楚。本试点研究的目的是确定黑人患者与白人患者肿瘤中基因和通路水平的变化，包括总体情况以及在二分BMI背景下的变化。
获取了一个单一机构的回顾性便利样本，样本为2级或3级子宫内膜样EC患者，在黑人和白人患者中平均分配。肿瘤样本采用Tempus Laboratories基于xT NGS的基因组分析测试进行分析。应用DESeq2来识别差异表达基因，然后进行 Ingenuity 通路分析（IPA）。连续变量使用不成对t检验进行分析，分类变量使用卡方检验和Fisher精确检验进行分析。
从2006年至2021年共识别并分析了39例代表性病例。基线临床病理特征相似。无论BMI如何，与白人患者相比，黑人患者肿瘤中有157个基因差异表达。IPA识别出BMI < 40 kg/m的黑人和白人患者之间有81条显著不同的通路，BMI≥40 kg/m的有117条。其中，有十一条通路无论BMI如何均持续且显著激活或失活。
EC中基因表达和通路激活在种族和BMI之间存在差异，这凸显了进一步研究的必要性，以便更好地理解这些差异对这一历史上未得到充分服务的患者群体中子宫内膜样EC进展、结局和治疗的影响。
