HSD17B4, ACAA1, and PXMP4 in Peroxisome Pathway Are Down-Regulated and Have Clinical Significance in Non-small Cell Lung Cancer

Abstract

To explore the potential functions and clinical significances of peroxisomes during lung cancer development and progression, we investigated the expressional profiles of peroxisome pathway genes and their correlations with clinical features in nonsmall cell lung cancer (NSCLC). The RNA-seq data of NSCLC including lung squamous carcinoma (LUSC) and lung adenocarcinoma (LUAD) patients with their clinical information were downloaded from The Cancer Genome Atlas (TCGA). Gene expression comparisons between tumor and normal samples were performed with edgeR package in R software and the results of the 83 peroxisome pathway genes were extracted. Through Venn diagram analysis, 38 common differentially expressed peroxisome pathway genes (C-DEPGs) in NSCLC were identified. Principal components analysis (PCA) was performed and the 38 C-DEPGs could discriminate NSCLC tumors from the non-tumor controls well. Through Kaplan-Meier survival and Cox regression analyses, 11 of the C-DEPGs were shown to have prognostic effects on NSCLC overall survival (OS) and were considered as key C-DEPGs (K-DEPGs). Through Oncomine, Human Protein Atlas (HPA) and the Clinical Proteomic Tumor Analysis Consortium (CPTAC), three K-DEPGs (HSD17B4, ACAA1, and PXMP4) were confirmed to be down-regulated in NSCLC at both mRNA and protein level. Their dyregulation mechanisms were revealed through their correlations with their copy number variations and methylation status. Their potential functions in NSCLC were explored through their NSCLC-specific co-expression network analysis, their correlations with immune infiltrations, immunomodulator gene expressions, MKI67 expression and their associations with anti-cancer drug sensitivity. Our findings suggested that HSD17B4, ACAA1, and PXMP4 might be new markers for NSCLC diagnosis and prognosis and might provide new clues for NSCLC treatment.

25-hydroxycholesterol Regulates Migration, Invasion and EMT of Colorectal Cancer through miR-92a-3p/ACAA1/NF-κB Pathway

“…Higher ACAA1 expression level correlates with the higher survival (41). The mechanisms of ACAA1 in cancers are involved in several immune-related process including phagocytosis, regulation of adaptive immune response, regulation of lymphocyte mediated immunity and ECM a liated (42). Consistently, in our study, RT-qPCR and Western blotting analysis results supported that ACAA1 was down-regulated in CRC tissues.…”

Development of a prognostic model for hepatocellular carcinoma using genes involved in aerobic respiration

“…Most of the genes included in our prognostic model have been reported to be associated with survival in many different malignancies. ACAA1 may be a marker for non-small cell lung cancer (NSCLC) diagnosis and prognosis, and may provide new insights for NSCLC treatment [ 14 ]. Up-regulation of ACAT1 expression is involved in the progression of colorectal cancer (CRC) [ 15 , 16 ].…”

ACAA1 Is a Predictive Factor of Survival and Is Correlated With T Cell Infiltration in Non-Small Cell Lung Cancer

“…Interestingly, Patsoukis and colleagues showed that PD-1 preserves effector T-cell function by inhibiting glycolysis and promoting fatty acid oxidation in CD4 + T cells through carnitine palmitoyltransferase I (CPT1A) (35). Besides predicting the efficacy of PD-1/PD-L1 inhibition, Zhang et al reported that the ACAA1 expression level was negatively correlated to several inhibitors, including Scr inhibitor (AZD0530), MEK1/2 inhibitor (AZD6244), EGFR inhibitor (Erlotinib), HER inhibitor (Lapatinib), and VEGFR2/3 inhibitor (ZD-6474) (36). Their findings reaffirmed the important role of ACAA1in predicting therapeutic efficacy.…”