Affiliation:
1. Ronin Institute Montclair New Jersey USA
2. Department of Pathology College of Medicine, University of South Alabama Mobile Alabama USA
3. Mitchell Cancer Institute, University of South Alabama Mobile Alabama USA
4. Mobile Infirmary Medical Center Mobile Alabama USA
5. Department of Mathematics and Statistics University of South Alabama Mobile Alabama USA
6. Department of Biochemistry and Molecular Biology University of South Alabama Mobile Alabama USA
Abstract
AbstractEarly detection, accurate monitoring, and therapeutics are major problems in non‐small‐cell lung cancer (NSCLC) patients. We identified genomic copy number variation of a unique panel of 40 mitochondria‐targeted genes in NSCLCs (GEOGSE #29365). Validation of mRNA expression of these molecules revealed an altered panel of 34 genes in lung adenocarcinomas (LUAD) and 36 genes in lung squamous cell carcinomas (LUSC). In the LUAD subtype (n = 533), we identified 29 upregulated and 5 downregulated genes, while in the LUSC subtype (n = 502), a panel of 30 upregulated and 6 downregulated genes were discovered. The majority of these genes are associated with mitochondrial protein transport, ferroptosis, calcium signaling, metabolism, OXPHOS function, TCA cycle, apoptosis, and MARylation. Altered mRNA expression of SLC25A4, ACSF2, MACROD1, and GCAT was associated with poor survival of the NSCLC patients. Progressive loss of SLC25A4 protein expression was confirmed in NSCLC tissues (n = 59), predicting poor survival of the patients. Forced overexpression of SLC25A4 in two LUAD cell lines inhibited their growth, viability, and migration. A significant association of the altered mitochondrial pathway genes with LC subtype‐specific classical molecular signatures was observed, implicating the existence of nuclear‐mitochondrial cross‐talks. Key alteration signatures shared between LUAD and LUSC subtypes including SLC25A4, ACSF2, MACROD1, MDH2, LONP1, MTHFD2, and CA5A could be helpful in developing new biomarkers and therapeutics.
Funder
University of South Alabama
Elsa U. Pardee Foundation
Subject
Genetics,Molecular Biology,Biochemistry,Biotechnology
Cited by
1 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献