Department of Gynecology, Nanjing First Hospital, Nanjing Medical University, Nanjing 210000, Jiangsu Province, China.
Aging (Albany NY). 2022 Jul 9;14(13):5554-5570. doi: 10.18632/aging.204168.
Endometrial cancer (EC) is one of the most common type of female genital malignancies. The purpose of the present study was to reveal the underlying oncogene and mechanism that played a pivotal role in postmenopausal EC patients.
Weighted gene co-expression network analysis (WGCNA) was conducted using the microarray dataset and clinical data of EC patients from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases to identify significant gene modules and hub genes associated with postmenopausal status in EC patients. LASSO regression was conducted to build and validate the risk model. Finally, expression of hub gene was validated in pre- and post-menopausal EC patients in our center.
1240 common genes were used to construct the WGCNA model. According to the WGCNA results, we identified a brown module with 471 genes which was significantly associated with postmenopausal status in EC patients. Furthermore, we constructed an 11-gene risk signature to predict the overall survival of EC patients. The Kaplan-Meier curve and area under the ROC curve (AUC) of this model showed high accuracy in prediction. We also validate the risk model in patients in our center and it also has a high accuracy. Among the 11 genes, PKD1 was recognized as a potential biomarker in the progression of EC patients with postmenopausal status.
Taken together, we uncovered a common PKD1-mediated mechanism underlying postmenopausal EC patients' progression by integrated analyses. This finding may improve targeted therapy for EC patients.
子宫内膜癌(EC)是女性生殖系统最常见的恶性肿瘤之一。本研究旨在揭示绝经后 EC 患者中发挥关键作用的潜在致癌基因和机制。
使用来自癌症基因组图谱(TCGA)和基因表达综合数据库(GEO)的 EC 患者的微阵列数据集和临床数据,进行加权基因共表达网络分析(WGCNA),以鉴定与 EC 患者绝经后状态相关的显著基因模块和枢纽基因。通过 LASSO 回归构建和验证风险模型。最后,在我们中心的绝经前和绝经后 EC 患者中验证了枢纽基因的表达。
共使用 1240 个共同基因构建 WGCNA 模型。根据 WGCNA 结果,我们确定了一个与 EC 患者绝经后状态显著相关的棕色模块,包含 471 个基因。此外,我们构建了一个 11 基因风险特征来预测 EC 患者的总生存率。该模型的 Kaplan-Meier 曲线和 ROC 曲线下面积(AUC)显示出较高的预测准确性。我们还在我们中心的患者中验证了该风险模型,它也具有较高的准确性。在这 11 个基因中,PKD1 被认为是绝经后 EC 患者进展的潜在生物标志物。
综上所述,我们通过综合分析揭示了绝经后 EC 患者进展的共同 PKD1 介导机制。这一发现可能为 EC 患者的靶向治疗提供改善。