Li Ning, Gao Li-Juan, Guo Ke-Xin, Wang Jie, Wang De-Ping, Hou Jia-Yi, Cao Ji-Min
Department of Gastrointestinal and Pancreatic Surgery & Hernia and Abdominal Surgery, Shanxi Provincial People's Hospital, Taiyuan, China.
MOE Key Laboratory of Cellular Physiology, Department of Physiology, Shanxi Medical University, Taiyuan, China.
BMC Cancer. 2025 Jul 1;25(1):1088. doi: 10.1186/s12885-025-14431-2.
BACKGROUND: There is an urgent need to identify more accurate and practical prognostic markers for improving the diagnosis and treatment outcomes of colorectal cancer (CRC). This study aimed to identify hub genes of CRC and to evaluate their clinical significance. METHODS: Proteomics analysis was performed on human CRC tissues and adjacent normal tissues, with bioinformatic screening applied to identify hub genes. Differential mRNA/protein expression of the hub genes between CRC tissues and adjacent tissues was validated using public databases combined with RT-qPCR. Potential upstream regulators of hub genes were predicted through integrated analysis of the TF-target database, Starbase, and Comparative Toxicogenomics Database (CTD). Protein expression levels of the hub genes were assessed in 100 tissues by immunohistochemistry (IHC)with semi-quantitative scoring. Prognostic utility of the screened hub genes was evaluated through receiver operating characteristic (ROC) curve analysis and overall survival (OS) stratification. RESULTS: NHP2 (a small nucleolar ribonucleoprotein) and PRPF4 (pre-mRNA processing factor 4) were identified as two hub genes/proteins in CRC. Both genes exhibited significant upregulation in CRC tissues at transcriptional and translational levels compared with adjacent tissues. ROC analysis demonstrated strong diagnostic potential: NHP2 AUC (area under curve) = 0.819 (95% CI: 0.639-0.958; P < 0.001) and PRPF4 AUC = 0.917 (95% CI: 0.785-1.000; P < 0.001). NHP2 and PRPF4 shared common regulators and exhibited a positive correlation in their expression levels.Clinically, patients with dual high expression of NHP2 and PRPF4 showed markedly reduced prognosis versus single-high or dual-low groups. CONCLUSIONS: Concurrent overexpression of NHP2 and PRPF4 is significantly associated with worse prognosis in CRC. Combined detection of NHP2 and PRPF4 is potentially a valuable prognostic marker of CRC compared to individual assessments. Our findings contribute to the growing body of evidence supporting multi-marker strategies for prognostic evaluation in CRC.
背景：迫切需要确定更准确、实用的预后标志物，以改善结直肠癌（CRC）的诊断和治疗效果。本研究旨在确定CRC的核心基因并评估其临床意义。 方法：对人CRC组织和相邻正常组织进行蛋白质组学分析，并应用生物信息学筛选来鉴定核心基因。使用公共数据库结合RT-qPCR验证CRC组织和相邻组织之间核心基因的差异mRNA/蛋白质表达。通过对转录因子-靶标数据库、Starbase和比较毒理基因组学数据库（CTD）的综合分析，预测核心基因的潜在上游调节因子。通过免疫组织化学（IHC）和半定量评分评估100个组织中核心基因的蛋白质表达水平。通过受试者工作特征（ROC）曲线分析和总生存期（OS）分层评估筛选出的核心基因的预后效用。 结果：NHP2（一种小核仁核糖核蛋白）和PRPF4（前体mRNA加工因子4）被鉴定为CRC中的两个核心基因/蛋白质。与相邻组织相比，这两个基因在CRC组织中的转录和翻译水平均显著上调。ROC分析显示出强大的诊断潜力：NHP2的曲线下面积（AUC）=0.819（95%CI：0.639-0.958；P<0.001），PRPF4的AUC=0.917（95%CI：0.785-1.000；P<0.001）。NHP2和PRPF4共享共同的调节因子，并且其表达水平呈正相关。临床上，NHP2和PRPF4双高表达的患者与单高或双低组相比，预后明显较差。 结论：NHP2和PRPF4的同时过表达与CRC的较差预后显著相关。与单独评估相比，联合检测NHP2和PRPF4可能是CRC的一种有价值的预后标志物。我们的研究结果为支持CRC预后评估多标志物策略的越来越多的证据做出了贡献。
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