RSRC1是宫颈癌中一种与疾病进展相关的候选生物标志物，其与p53/CDK2相关的细胞周期信号通路存在关联。

Abstract

RSRC1 rises progressively from normal cervix through CIN1–CIN3 to invasive cancer. • High RSRC1 expression predicts shorter overall survival in the TCGA-CESC cohort. • Two independent siRNAs cut proliferation and migration in SiHa and CaSki cells. • RSRC1 loss causes G2/M arrest with higher p53 and lower CDK2 in both cell lines. • Stable RSRC1 knockdown suppresses xenograft growth; CDK2 rescue reverses arrest. Cervical cancer (CC) remains a leading cause of cancer-related death among women, and the outlook for patients with advanced, recurrent or persistent disease is poor. Molecular markers that track disease progression and expose pharmacologically tractable vulnerabilities are therefore needed. GSE63514 and GSE138080 were used for exploratory candidate generation and cohort-specific disease-stage and discrimination analyses; random forest analysis was restricted to candidate prioritization. Prognostic relevance was assessed in TCGA-CESC (n = 304). Two independent siRNAs silenced RSRC1 in SiHa and CaSki cells, followed by viability, DNA synthesis, migration, cell-cycle and p53/CDK2 analyses. CDK2 overexpression, treatment with the p53 inhibitor pifithrin-α and a stable shRNA xenograft model evaluated pathway involvement and in vivo effects. RSRC1 expression increased across cervical disease stages. In GSE138080, RSRC1 discriminated cervical squamous cell carcinoma from non-carcinoma samples (area under the curve = 0.972, 95% confidence interval 0.925–1.000). High RSRC1 expression was associated with shorter overall survival (hazard ratio = 2.45, 95% confidence interval 1.55–3.87; P < 0.001) and remained independently associated after multivariable adjustment. In both cell lines, either siRNA reduced viability, DNA synthesis and migration, induced G2/M accumulation, increased p53 and decreased CDK2. CDK2 overexpression or pifithrin-α partially reversed these phenotypes. Stable RSRC1 depletion slowed xenograft growth, reduced Ki-67 and CDK2, and increased p53. RSR