Hu Meng, Dong Haotian, Chen Chujia, Ye Chengyuan, Yan Jianing, Yu Xuan, Ye Guoliang, Shao Yongfu
Department of Gastroenterology, The First Affiliated Hospital of Ningbo University, Ningbo, 315020, China.
Health Science Center, Ningbo University, Ningbo, 315211, China.
Sci Rep. 2025 Jul 11;15(1):25039. doi: 10.1038/s41598-025-10354-x.
The prognosis of advanced CRC is poor, and identifying key genes related to CRC is vital for improving CRC prognosis. Our research used univariate Cox analysis and Mendelian randomization (MR) analysis to identify key prognostic genes in CRC. Multiple datasets such as the nomogram model and single-cell sequencing (scRNA-seq) were used to investigate the potential molecular mechanisms of the key genes. The expression levels were confirmed by using quantitative real-time polymerase chain reaction (qRT-PCR). The biological functions and effect on prognosis of the identified prognostic genes were also explored. MMRN1 and SLC6A19 were identified as key prognostic genes for CRC. Subsequently, the nomogram model demonstrated that MMRN1 and SLC6A19 can strongly predict survival. Further examination with multiple datasets elucidated the potential molecular mechanisms of the key prognostic genes, revealing a close association with immune cell infiltration. MMRN1 is enriched in classic CRC signaling pathways, whereas SLC6A19 is enriched in metabolism-related pathways. They are closely linked to immune cell infiltration levels and significantly influence the immune microenvironment in CRC. These key prognostic genes are significantly correlated with chemotherapeutic drug sensitivity and present promising opportunities for CRC therapy. The expression of both key genes was also observed in the scRNA-seq data of CRC. Finally, qRT-PCR validation revealed that MMRN1 is markedly downregulated and SLC6A19 is significantly upregulated in CRC. Lower expression of MMRN1 and higher expression of SLC6A19 significantly promoted the proliferation and metastasis of colorectal cancer cells. Our study identified MMRN1 and SLC6A19 as potential key prognostic genes for CRC, as they can reliably predict the prognosis of CRC. Furthermore, the potential molecular mechanisms of MMRN1 and SLC6A19 were revealed, suggesting new drug targets and therapeutic directions for managing prognosis.
晚期结直肠癌的预后较差，识别与结直肠癌相关的关键基因对于改善结直肠癌的预后至关重要。我们的研究使用单变量Cox分析和孟德尔随机化（MR）分析来识别结直肠癌中的关键预后基因。使用了多种数据集，如列线图模型和单细胞测序（scRNA-seq）来研究关键基因的潜在分子机制。通过定量实时聚合酶链反应（qRT-PCR）来确认表达水平。还探讨了所识别的预后基因的生物学功能及其对预后的影响。MMRN1和SLC6A19被确定为结直肠癌的关键预后基因。随后，列线图模型表明MMRN1和SLC6A19能够强烈预测生存率。使用多个数据集进行的进一步研究阐明了关键预后基因的潜在分子机制，揭示了其与免疫细胞浸润的密切关联。MMRN1在经典的结直肠癌信号通路中富集，而SLC6A19在代谢相关通路中富集。它们与免疫细胞浸润水平密切相关，并显著影响结直肠癌中的免疫微环境。这些关键预后基因与化疗药物敏感性显著相关，为结直肠癌治疗提供了有前景的机会。在结直肠癌的scRNA-seq数据中也观察到了这两个关键基因的表达。最后，qRT-PCR验证显示，在结直肠癌中MMRN1明显下调，SLC6A19明显上调。MMRN1低表达和SLC6A19高表达显著促进了结肠癌细胞的增殖和转移。我们的研究确定MMRN1和SLC6A19为结直肠癌潜在的关键预后基因，因为它们能够可靠地预测结直肠癌的预后。此外，揭示了MMRN1和SLC6A19的潜在分子机制，为管理预后提供了新的药物靶点和治疗方向。
