Abstract Body (Do not enter title and authors here): Background: Acute Type A Aortic Dissection (ATAAD) is a lethal disease with limited predictability globally. Cancer, a severe public health issue worldwide, has now become the second leading cause of death in America. In this study, we aimed to explore potential common mechanisms and therapeutic targets between ATAAD and cancer.
Aims: Identify mitochondrial-related diagnostic biomarkers of ATAAD and their roles in various cancers.
Methods: ATAAD-related datasets GSE52093, GSE98770, GSE190635 were downloaded from GEO and merged after removing batch effects. We verified 119 mitochondrial-related differentially expressed genes (DEGs), followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Using five machine learning methods (LASSO, SVM, Decision Tree, Random Forest, and Boruta algorithm), we identified two mitochondrial-related diagnostic biomarkers of ATAAD: PPIF and CASQ1. The diagnostic accuracy was performed using receiver operating characteristic (ROC) curves. RT-qPCR was used to detect PPIF and CASQ1 expression. Immune infiltration analysis suggested that PPIF may play a key role in tumor immune microenvironment. We utilized TCGA and GTEx databases, Kaplan-Meier analyses and Cox regression analyses to assess PPIF expression and survival analysis in 33 cancer types. qPCR and Western Blot (WB) assays verified PPIF overexpression in lung adenocarcinoma (LUAD) and uterine corpus endometrial carcinoma (UCEC). CCK-8, wound-healing and transwell assays further verified PPIF’s proliferative, migratory and invasive abilities in LUAD and UCEC.
Results: Our study identified PPIF and CASQ1 as hub mitochondrial-related diagnostic biomarkers of ATAAD. Besides its close association with tumor immune infiltration, PPIF also overexpressed in multiple cancer types. Survival analysis suggested the prognostic value of PPIF in most cancers. Experimental results further verified that PPIF promotes the proliferation, migration, and invasion of LUAD and UCEC.
Conclusions: PPIF and CASQ1 are potential mitochondrial-related diagnostic biomarkers of ATAAD, not previously reported. Pan-cancer analysis implies that PPIF may serve as a key prognostic and therapeutic target in multiple cancers. PPIF may act as a hub gene linking ATAAD and cancer, offering new insights to reduce ATAAD incidence in cancer patients.