我们试图通过整合基因表达和蛋白质组学数据来鉴定高级别浆液性卵巢癌(HGSC)的新分子亚型,并寻找卵巢癌的潜在生物学特征以改善临床结果。
iCluster方法用于分析TCGA和临床蛋白质组学肿瘤分析联盟数据库之间的131个常见HGSC样品。Kaplan-Meier存活曲线用于估计患者的总生存期,并使用对数秩检验评估存活曲线的差异。
确定了两种具有不同总生存期(P=.00114)和不同铂状态(P=.0061)的新型卵巢癌亚型。选择18种信使RNA和38种蛋白质作为亚型之间的差异分子。通路分析显示致心律失常性右心室心肌病通路在这两种亚型和桥粒钙粘蛋白DSG2、DSP、JUP,与II亚型相比,该途径中的PKP2在I亚型中过表达。
我们的研究扩展了高级别浆液性卵巢癌的潜在预后相关生物学特征。在铂敏感患者中,桥粒钙粘蛋白的富集增加了HGSC预后的风险,该结果指导了铂类敏感性卵巢癌患者治疗方案的修订,以改善结局.
We sought to identify novel molecular subtypes of high-grade serous ovarian cancer (HGSC) by the integration of gene expression and proteomics data and to find the underlying biological characteristics of ovarian cancer to improve the clinical outcome.
The iCluster method was utilized to analysis 131 common HGSC samples between TCGA and Clinical Proteomic Tumor Analysis Consortium databases. Kaplan-Meier survival curves were used to estimate the overall survival of patients, and the differences in survival curves were assessed using the log-rank test.
Two novel ovarian cancer subtypes with different overall survival (P = .00114) and different platinum status (P = .0061) were identified. Eighteen messenger RNAs and 38 proteins were selected as differential molecules between subtypes. Pathway analysis demonstrated arrhythmogenic right ventricular cardiomyopathy pathway played a critical role in the discrimination of these two subtypes and desmosomal cadherin DSG2, DSP, JUP, and PKP2 in this pathway were overexpression in subtype I compared with subtype II.
Our study extended the underlying prognosis-related biological characteristics of high-grade serous ovarian cancer. Enrichment of desmosomal cadherin increased the risk for HGSC prognosis among platinum-sensitive patients, the results guided the revision of the treatment options for platinum-sensitive ovarian cancer patients to improve outcomes.