RNA binding proteins (RBPs) have been implicated in oncogenesis and progression in various cancers. However, the potential value of RBPs as prognostic indicators and therapeutic targets in colorectal cancer (CRC) requires further investigation. Four thousand eighty two RBPs were collected from literature. The weighted gene co-expression network analysis (WGCNA) was performed to identify prognosis-related RBP gene modules based on the data attained from the TCGA cohorts. LASSO algorithm was conducted to establish a prognostic risk model, and the validity of the proposed model was confirmed by an independent GEO dataset. Functional enrichment analysis was performed to reveal the potential biological functions and pathways of the signature and to estimate tumor immune infiltration. Potential therapeutic compounds were inferred utilizing CMap database. Expressions of hub genes were further verified through the Human Protein Atlas (HPA) database and RT-qPCR. One thousand seven hundred thirty four RBPs were differently expressed in CRC samples and 4 gene modules remarkably linked to the prognosis were identified, based on which a 12-gene signature was established for prognosis prediction. Multivariate Cox analysis suggested this signature was an independent predicting factor of overall survival (P < 0.001; HR:3.682; CI:2.377–5.705) and ROC curves indicated it has an effective predictive performance (1-year AUC: 0.653; 3-year AUC:0.673; 5-year AUC: 0.777). GSEA indicated that high risk score was correlated with several cancer-related pathways, including cytokine-cytokine receptor cross talk, ECM receptor cross talk, HEDGEHOG signaling cascade and JAK/STAT signaling cascade. ssGSEA analysis exhibited a significant correlation between immune status and the risk signature. Noscapine and clofazimine were screened as potential drugs for CRC patients with high-risk scores. TDRD5 and GPC1 were identified as hub genes and their expression were validated in 15 pairs of surgically resected CRC tissues. Our research provides a depth insight of RBPs’ role in CRC and the proposed signature are helpful to the personalized treatment and prognostic judgement.

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基于 WGCNA 的结直肠癌预后预测 RBP 基因特征的开发和验证

RNA 结合蛋白 (RBP) 与各种癌症的发生和发展有关。然而，RBP 作为结直肠癌 (CRC) 的预后指标和治疗靶点的潜在价值需要进一步研究。从文献中收集了四千八十二个 RBP。基于从 TCGA 队列获得的数据，进行加权基因共表达网络分析 (WGCNA) 以识别与预后相关的 RBP 基因模块。采用 LASSO 算法建立了预后风险模型，并通过独立的 GEO 数据集证实了所提出模型的有效性。进行功能富集分析以揭示特征的潜在生物学功能和途径并估计肿瘤免疫浸润。利用 CMap 数据库推断出潜在的治疗化合物。通过人类蛋白质图谱 (HPA) 数据库和 RT-qPCR 进一步验证了 hub 基因的表达。1734 个 RBP 在 CRC 样本中表达不同，并鉴定出 4 个与预后显着相关的基因模块，基于这些模块建立了用于预后预测的 12 个基因标签。多变量 Cox 分析表明该特征是总生存期的独立预测因素（P < 0.001；HR：3.682；CI：2.377–5.705），ROC 曲线表明它具有有效的预测性能（1 年 AUC：0.653；3 年AUC：0.673；5 年 AUC：0.777）。GSEA 表明高风险评分与多种癌症相关通路相关，包括细胞因子-细胞因子受体串扰、ECM 受体串扰、HEDGEHOG 信号级联和 JAK/STAT 信号级联。ssGSEA 分析显示免疫状态与风险特征之间存在显着相关性。Noscapine 和氯法齐明被筛选为具有高风险评分的 CRC 患者的潜在药物。TDRD5 和 GPC1 被确定为中枢基因，并在 15 对手术切除的 CRC 组织中验证了它们的表达。我们的研究深入了解了 RBP 在 CRC 中的作用，所提出的特征有助于个性化治疗和预后判断。