School of Basic Medical Sciences, Anhui Medical University, 230032 Hefei, Anhui, China.
Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, 230022 Hefei, Anhui, China.
Int J Med Sci. 2021 Jan 1;18(3):672-684. doi: 10.7150/ijms.53243. eCollection 2021.
The cell division cycle-associated (CDCA) protein family plays a pivotal role in the regulation of the cell cycle during tumorigenesis and predicts the prognosis of tumors, but an analysis of these proteins in pancreatic adenocarcinoma (PAAD) is still lacking. Oncomine and GEPIA were used to observe the expression and prognostic value of eight CDCAs in pan-cancer. Univariate Cox analysis of single CDCAs and multivariate Cox analysis of all eight CDCAs were performed to evaluate the integrated prognostic value of CDCAs, and the results are displayed as hazard ratios (HRs) and 95% confidence intervals (95% CIs). K-M plots and receiver operating characteristics curves were used to display the predicted function and accuracy of CDCAs to determine the risk score. Annotation of CDCA-related genes, gene sets enrichment analysis (GSEA) and gene sets variation analysis (GSVA) were performed to reveal the CDCAs that impact biological processes. CDCAs expression in most tumors is higher than that in normal tissues and is associated with a poor prognosis. Regarding PAAD, increased CDCA expression along with advanced PAAD tumor stage, NUF2, CDCA2, CDCA3, CDCA4 and CDCA5 expression are risk factors for poor prognosis, while CBX2 expression is a protective factor (P < 0.05). The integrated prognostic value of CDCAs in PAAD patients was validated by SurvExpress in the TCGA-PAAD cohort (P < 0.001, HR = 2.16, 95% CI = 1.41-3.3) and the ICGC-PACA cohort (P < 0.001, HR = 2.56, 95% CI = 1.73-3.79). Genetic alteration and DNA methylation of CDCAs might not affect the prognosis of PAAD patients. After comparing high- and low-risk groups separated by CDCA risk scores, the activated pathways were revealed and included the cell cycle, DNA repair, P53, MYC-targets, E2F-targets and PI3K pathways. CDCAs can predict the OS prognosis of PAAD patients. The cell cycle, DNA repair, E2F, P53 and PI3K signaling pathways, in which CDCAs are involved, impact the tumorigenesis of PAAD.
细胞分裂周期相关(CDCA)蛋白家族在肿瘤发生过程中对细胞周期的调节起着关键作用,并预测肿瘤的预后,但对胰腺导管腺癌(PAAD)中这些蛋白的分析仍存在空白。Oncomine 和 GEPIA 用于观察泛癌中 8 个 CDCA 的表达和预后价值。对单个 CDCA 进行单因素 Cox 分析,对所有 8 个 CDCA 进行多因素 Cox 分析,评估 CDCA 的综合预后价值,结果以风险比(HR)和 95%置信区间(95%CI)表示。K-M 图和受试者工作特征曲线用于显示 CDCA 预测功能和准确性,以确定风险评分。注释 CDCA 相关基因,进行基因集富集分析(GSEA)和基因集变异分析(GSVA),以揭示影响生物学过程的 CDCA。大多数肿瘤中 CDCA 的表达高于正常组织,且与预后不良相关。在 PAAD 中,CDCA 表达增加以及 PAAD 肿瘤分期进展、NUF2、CDCA2、CDCA3、CDCA4 和 CDCA5 表达是预后不良的危险因素,而 CBX2 表达是保护因素(P<0.05)。TCGA-PAAD 队列中的 SurvExpress 验证了 CDCA 在 PAAD 患者中的综合预后价值(P<0.001,HR=2.16,95%CI=1.41-3.3)和 ICGC-PACA 队列(P<0.001,HR=2.56,95%CI=1.73-3.79)。CDCA 的遗传改变和 DNA 甲基化可能不会影响 PAAD 患者的预后。比较 CDCA 风险评分分离的高低风险组后,揭示了激活的途径,包括细胞周期、DNA 修复、P53、MYC 靶点、E2F 靶点和 PI3K 途径。CDCA 可预测 PAAD 患者的 OS 预后。CDCA 参与的细胞周期、DNA 修复、E2F、P53 和 PI3K 信号通路影响 PAAD 的肿瘤发生。