Zhou Zhengwei, Gao Fei, Lei Han, Wen Haixuan, Tang Jiaxi, Peng Yulong, Fan Lili, Xu Lu, Shu Guang
Department of Pathology, School of Basic Medicine, Central South University, Changsha, Hunan, China.
Department of Pathology, First Affiliated Hospital of Jinan University, Guangzhou 510630, China.
J Cancer. 2025 Jun 23;16(9):2959-2969. doi: 10.7150/jca.110271. eCollection 2025.
Emerging evidence suggests that aberrant alternative splicing plays a vital role in the development of tumors. However, the expression of splicing factors (SF) in colorectal cancer and its relationship with prognosis is still unclear. Here, we divided patients into high-risk and low-risk groups through univariate COX analysis and LASSO regression analysis, and selected 13 alternative splicing factors that are highly correlated with prognosis for subsequent analysis. We systematically analyzed the prognostic value of transcription levels of SFs in colorectal cancer (CRC) and found that RAB3A interacting protein (RAB3IP), programmed cell death 4 (PDCD4), golgin B1 (GOLGB1), and neuregulin 4 (NRG4) as the most predictive markers for the prognosis of CRC. After comparing the expression of four splicing factors in cancer tissues with normal tissues as well as OS analysis, it is strongly indicated that only RAB3IP demonstrates a significant positive correlation with favorable prognosis. Accordingly, we established a risk signature of transcription levels of RAB3IP as an independent prognostic marker for CRC. Moreover, by the Gene Set Enrichment Analysis (GSEA), we demonstrated that the RAB3IP was correlated to Cell Cycle, WNT pathway and Spliceosome in cancer. In conclusion, our findings demonstrate that SFs play a critical role in CRC pathogenesis, and identify RAB3IP as a novel prognostic biomarker for CRC.
新出现的证据表明，异常可变剪接在肿瘤发生发展中起着至关重要的作用。然而，剪接因子（SF）在结直肠癌中的表达及其与预后的关系仍不清楚。在此，我们通过单变量COX分析和LASSO回归分析将患者分为高风险和低风险组，并选择了13个与预后高度相关的可变剪接因子进行后续分析。我们系统地分析了SF转录水平在结直肠癌（CRC）中的预后价值，发现RAB3A相互作用蛋白（RAB3IP）、程序性细胞死亡4（PDCD4）、高尔基体蛋白B1（GOLGB1）和神经调节蛋白4（NRG4）是CRC预后最具预测性的标志物。在比较癌组织和正常组织中四种剪接因子的表达以及进行总生存期（OS）分析后，强烈表明只有RAB3IP与良好预后呈显著正相关。因此，我们建立了RAB3IP转录水平的风险特征作为CRC的独立预后标志物。此外，通过基因集富集分析（GSEA），我们证明RAB3IP在癌症中与细胞周期、WNT通路和剪接体相关。总之，我们的研究结果表明SF在CRC发病机制中起关键作用，并将RAB3IP鉴定为CRC一种新的预后生物标志物。
