文献类型：期刊文献

英文题名：A Novel Mitochondria-Associated Programmed Cell Death-Related Prognostic Model and Validation of Oncogene INHBB in Colorectal Cancer

作者：Sun, Yanqing[1];Gao, Chun[2];Jia, Dong[2];Ma, Qiang[2];Wang, Wei[2]

第一作者：孙永强

通信作者：Ma, Q[1];Wang, W[1]

机构：[1]Gansu Univ Chinese Med, Clin Med Coll 1, Lanzhou, Gansu, Peoples R China;[2]940th Hosp Joint Support Force, Dept Gastroenterol, Lanzhou, Gansu, Peoples R China

第一机构：甘肃中医药大学

通信机构：[1]corresponding author), 940th Hosp Joint Support Force, Dept Gastroenterol, Lanzhou, Gansu, Peoples R China.

年份：2025

卷号：2025

期号：1

外文期刊名：INTERNATIONAL JOURNAL OF GENOMICS

收录：;Scopus(收录号：2-s2.0-105023499614);WOS:【SCI-EXPANDED(收录号:WOS:001623253300001)】；

基金：This study was funded by the Key Research and Development Program of Gansu Province, No. 24YFFA069.

语种：英文

外文关键词：colorectal cancer; immune infiltration; mitochondrial; programmed cell death

摘要：ObjectiveThe objective of this study is to explore mitochondria-associated programmed cell death (mtPCD)-related key biomarkers for patients with colorectal cancer (CRC).MethodsCRC-related datasets were obtained from the GEO and TCGA databases, and mitochondria-related genes (MitoRGs) and PCD-related genes (PCDRGs) were acquired from the MitoCarta database or pertinent literature. After differentially expressed gene (DEG) screening, the DEmtPCD coexpressed genes were identified. Then, consensus clustering analysis was conducted, followed by GSEA and immune infiltration analysis. In addition, a prognostic model was constructed, and then, immune infiltration analysis, GSEA, and drug sensitivity analysis were carried out. The qRT-PCR and western blot were employed to determine the expression of key genes. Finally, a loss-of-function experiment was applied to investigate the influence of INHBB on CRC in vitro.ResultsA total of 2118 DEGs were screened, and then, 64 DEmtPCD coexpressed genes were obtained. Subsequently, two clusters, including C1 and C2, were identified, and patients in the C1 group had better survival outcomes. In addition, a prognostic model was constructed based on four key genes, namely, ACSL6, INHBB, GPR15, and SRPX. Also, the area under the curves (AUCs) for overall survival (OS) at 1, 3, and 5 years were 0.667, 0.665, and 0.603 in the TCGA set, separately, and 0.759, 0.766, and 0.662, separately, in the GSE17537 dataset. The total fraction of nine immune cells showed a significant difference between the low- (L) and high (H)-risk groups, such as neutrophils, activated NK cells, and activated dendritic cells. Also, there was a significant difference in TIDE scores between the H- and L-risk groups, and APC was the most significantly mutated gene in both the H- and L-risk groups. IC50 value of some chemotherapeutic agents showed a significant difference between the L- and H-risk groups, containing AZD1332-1463, IGF1R-3801-1738, and XAV939-1268. The expression levels of ACSL6, GPR15, and INHBB were significantly elevated in CRC cells compared to those in NCM460 cells, while SRPX significantly decreased. Notably, downregulation of INHBB effectively alleviated the tumorigenesis of SW620 cells.ConclusionA prognostic model was constructed based on four key mtPCD-associated genes, namely, ACSL6, INHBB, GPR15, and SRPX. INHBB was upregulated in CRC, and the alleviation of INHBB suppressed the proliferation and migration of CRC cells.