Zhang Bomiao, Xia Mingyu, Zhao Shihui, Li Yien, Yu Chenfeng, Song Liqiang, Wang Shaoke, Cui Binbin
Department of Colorectal Surgery, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, China.
Curr Med Chem. 2024 Oct 7. doi: 10.2174/0109298673335900240920070746.
Explore the role of mitochondrial membrane permeability transition (MPT) in colon adenocarcinoma (COAD).
Further exploration of risk stratification for COAD prognostic assessment has important clinical value. MPT-related pathways play a key role in the pathogenesis of many human diseases, including tumorigenesis. Its impact on COAD is still unknown.
Bioinformatics analysis was conducted by analyzing the GEO database and TCGA database, and the bioinformatics results were verified by in vitro experiments.
Through the analysis of the transcriptome data of 1008 COAD samples in the GEO database and TCGA database, the differential expressions of MPT-related genes in COAD were explored, followed by molecular subtype analysis based on MPT characteristics by univariate Cox algorithm analysis and the consensus clustering algorithm. The gene signature associated with MPT molecular subtypes was further identified and the MPT scoring system was established by the LASSO-univariate Cox analysis algorithm. After evaluating the prognostic value of the MPT scoring system in COAD patients via nomogram establishment, the clinical value of the MPT scoring system was comprehensively analyzed through somatic mutation characteristics analysis, immunotherapy response analysis, immunoinfiltration analysis, and drug sensitivity analysis. CCK-8, WB, PCR, colony formation method, and Transwell method were used to verify the effect of the screened target on the proliferation and invasion of COAD cells.
We successfully established a scoring system related to MPT and validated the prognostic value of COAD patients. The potential clinical value of the MPT scoring system was also analyzed. VSIG4 was selected for further in vitro experiments to verify the effect of the screened targets on the proliferation and invasion ability of COAD cells.
We established an MPT scoring system for effective risk stratification of COAD patients, demonstrating the impact of MPT on the development of COAD and its potential value as an intervention factor.
探讨线粒体膜通透性转换（MPT）在结肠腺癌（COAD）中的作用。
进一步探索COAD预后评估的风险分层具有重要的临床价值。MPT相关通路在包括肿瘤发生在内的许多人类疾病的发病机制中起关键作用。其对COAD的影响尚不清楚。
通过分析GEO数据库和TCGA数据库进行生物信息学分析，并通过体外实验验证生物信息学结果。
通过分析GEO数据库和TCGA数据库中1008例COAD样本的转录组数据，探索COAD中MPT相关基因的差异表达，随后通过单变量Cox算法分析和一致性聚类算法基于MPT特征进行分子亚型分析。通过LASSO-单变量Cox分析算法进一步鉴定与MPT分子亚型相关的基因特征并建立MPT评分系统。通过建立列线图评估MPT评分系统在COAD患者中的预后价值后，通过体细胞突变特征分析、免疫治疗反应分析、免疫浸润分析和药物敏感性分析全面分析MPT评分系统的临床价值。采用CCK-8、WB、PCR、集落形成法和Transwell法验证筛选出的靶点对COAD细胞增殖和侵袭的影响。
我们成功建立了与MPT相关的评分系统，并验证了其对COAD患者的预后价值。还分析了MPT评分系统的潜在临床价值。选择VSIG4进行进一步的体外实验，以验证筛选出的靶点对COAD细胞增殖和侵袭能力的影响。
我们建立了一个MPT评分系统，用于对COAD患者进行有效的风险分层，证明了MPT对COAD发展的影响及其作为干预因素的潜在价值。
