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Background: Mitochondrial permeability transition-driven necrosis (MPTDN) hasbeen implicated in a variety of diseases, but its relationship with colorectal cancer(CRC) prognosis is unclear.Methods: In this study, TCGA-COAD and TCGA-READ datasets were analyzed toidentify differentially expressed genes (DEGs) in CRCs. Differentially expressedMPTDNGRs (DE-MPTDNRGs) were identified by comparing DEGs to MPTDNrelatedgenes (MPTDNRGs). Univariate Cox, Minimum Absolute Contraction andSelection Operator (LASSO) regression and risk scoring analysis divided TCGACRCpatients into high- and low-risk cohorts.Results: The prognostic genes LMNB2, CASP7, PRKCB, GZMB and ENDOG wereidentified, and the survival rate of high-risk patients was poor. Independentprognostic factors, including risk score, age, and N stage, are effectivepredictors of survival. Immunoassays revealed that high-risk patients had 9elevated immune checkpoints, while low-risk patients were more susceptible topazopanib and temsirolimus. In addition, single-cell analysis showed that PRKCBand GZMB were highly expressed in stem cells, while LMNB2 was moreabundantly expressed in mast cells. Real-time PCR (RT-qPCR) confirmed lowlevels of CASP7, PRKCB, and ENDOG mRNA in CRC tissues, with no significantdifference between LMNB2 and GZMB.Conclusion: These findings highlight 5 MPTDN-associated prognostic genes inCRC, providing insights for individualized treatment and prognosis.
背景:线粒体通透性转换孔介导的坏死(Mitochondrial permeability transition-driven necrosis, MPTDN)已被证实与多种疾病相关,但其与结直肠癌(colorectal cancer, CRC)预后的关联尚未明确。 方法:本研究对TCGA-COAD与TCGA-READ数据集进行分析,以鉴定结直肠癌组织中的差异表达基因(differentially expressed genes, DEGs)。通过将差异表达基因与线粒体通透性转换孔介导坏死相关基因(MPTDN-related genes, MPTDNRGs)进行比对,筛选得到差异表达的MPTDN相关基因(DE-MPTDNRGs)。采用单因素Cox回归、最小绝对收缩和选择算子(Least Absolute Shrinkage and Selection Operator, LASSO)回归及风险评分分析,将TCGA结直肠癌患者划分为高风险队列与低风险队列。 结果:本研究鉴定得到5个与预后相关的基因,分别为LMNB2、CASP7、PRKCB、GZMB及ENDOG;高风险队列患者的生存率显著更低。风险评分、年龄及N分期等独立预后因素可有效预测患者生存情况。免疫检测结果显示,高风险队列患者存在9个上调的免疫检查点(immune checkpoints),而低风险队列患者对帕唑帕尼(pazopanib)与替西罗莫司(temsirolimus)的敏感性更高。此外,单细胞分析结果表明,PRKCB与GZMB在干细胞中呈高表达,而LMNB2在肥大细胞中的表达更为丰富。实时荧光定量聚合酶链反应(Real-time PCR, RT-qPCR)验证显示,结直肠癌组织中CASP7、PRKCB及ENDOG的信使RNA(messenger RNA, mRNA)水平较低,而LMNB2与GZMB的表达无显著差异。 结论:本研究揭示了5个与结直肠癌相关的线粒体通透性转换孔介导坏死预后基因,可为结直肠癌的个体化治疗与预后评估提供新思路。



