Xu Chao, Li ShuYuan, Chen HongYuan, Chi LiangJie, Wang XiangYu, He Muzhen, Wang Qingshui, Zhang Xiuli, Lin Yao, Xue FangQin
Department of Gastrointestinal Surgery, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, No. 134 Dongjie, Fuzhou, China.
Department of Radiology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, No. 134 Dongjie, Fuzhou, China.
J Cancer. 2024 Oct 28;15(20):6724-6739. doi: 10.7150/jca.102605. eCollection 2024.
Colorectal cancer remains a formidable global health challenge, characterized by high recurrence rates and poor prognosis. This study introduces a novel Recurrence Related Gene Signature (RRGS), designed to predict therapy response and enhance prognostic accuracy in colorectal cancer. Through analysis of the GSE17536 cohort, we identified 79 differentially expressed genes (DEGs) between recurrent and non-recurrent cases, comprising 54 upregulated and 25 downregulated genes. Pathway analysis revealed that upregulated genes were enriched in cancer progression-related pathways, while downregulated genes were associated with immune-related processes. Leveraging these findings, we developed the RRGS using LASSO regression, resulting in an innovative 11-gene model with robust diagnostic and prognostic capabilities. Notably, the RRGS demonstrated significant predictive value for both overall survival and disease-free survival across multiple datasets, with higher RRGS scores correlating with advanced tumor stages and poorer outcomes, particularly in post-chemotherapy patients. This predictive power highlights the RRGS's potential in guiding personalized treatment strategies. Furthermore, we identified STC1 as a critical component of the RRGS, playing a significant role in tumor progression and immune evasion. Through rigorous and experiments we confirmed that STC1 knockdown substantially reduced cell proliferation and metastasis, emphasizing its potential as a therapeutic target. This comprehensive study not only elucidates the molecular mechanisms driving colorectal cancer recurrence but also introduces a powerful tool for enhancing prognostic accuracy and personalizing therapeutic interventions.
结直肠癌仍然是一项严峻的全球健康挑战,其特征是复发率高且预后较差。本研究引入了一种新型的复发相关基因特征(RRGS),旨在预测结直肠癌的治疗反应并提高预后准确性。通过对GSE17536队列的分析,我们在复发和未复发病例之间鉴定出79个差异表达基因(DEG),其中包括54个上调基因和25个下调基因。通路分析表明,上调基因在癌症进展相关通路中富集,而下调基因与免疫相关过程有关。利用这些发现,我们使用LASSO回归开发了RRGS,从而产生了一个具有强大诊断和预后能力的创新型11基因模型。值得注意的是,RRGS在多个数据集中对总生存期和无病生存期均显示出显著的预测价值,RRGS得分越高,与肿瘤晚期和较差的预后相关,尤其是在化疗后患者中。这种预测能力突出了RRGS在指导个性化治疗策略方面的潜力。此外,我们确定STC1是RRGS的关键组成部分,在肿瘤进展和免疫逃逸中发挥重要作用。通过严格的实验,我们证实敲低STC1可显著降低细胞增殖和转移,强调了其作为治疗靶点的潜力。这项全面的研究不仅阐明了驱动结直肠癌复发的分子机制,还引入了一种强大的工具,用于提高预后准确性和使治疗干预个性化。