PAXIP1-AS1 is associated with immune infiltration and predicts poor prognosis in ovarian cancer

Abstract

The long non-coding RNA (LncRNA) PAXIP1 antisense RNA 1 (PAXIP1-AS1) was found to promote proliferation, migration, EMT, and apoptosis of ovarian cancer (OC) cells in OC cell lines, but the relationship between PAXIP1-AS1 expression and clinical characteristics, prognosis, and immune infiltration of OC patients and its regulatory network are unclear. 379 OC tissues were collected from The Cancer Genome Atlas (TCGA) database. 427 OC tissues and 88 normal ovarian tissues were collected from GTEx combined TCGA database. 130 OC samples were collected from GSE138866. Kruskal-Wallis test, Wilcoxon sign-rank test, logistic regression, Kaplan-Meier method, Cox regression analysis, Gene set enrichment analysis (GSEA), and immuno-infiltration analysis were used to evaluate the relationship between clinical characteristics and PAXIP1-AS1 expression, prognostic factors, and determine the significant involvement of PAXIP1-AS1 in function. QRT-PCR was used to validate the expression of PAXIP1-AS1 in OC cell lines. Low PAXIP1-AS1 expression in OC was associated with age (P = 0.045), histological grade (P = 0.011), and lymphatic invasion (P = 0.004). Low PAXIP1-AS1 expression predicted a poorer overall survival (OS) (HR: 0.71; 95% CI: 0.55–0.92; P = 0.009), progression free interval (PFS) (HR: 1.776; 95% CI: 1.067–2.955; P = 0.001) and disease specific survival (DSS) (HR: 0.67; 95% CI: 0.51–0.89; P = 0.006). PAXIP1-AS1 expression (HR: 0.711; 95% CI: 0.542–0.934; P = 0.014) was independently correlated with PFS in OC patients. GSEA demonstrated that neutrophil degranulation, signaling by Interleukins, GPCR-ligand binding, G alpha I signaling events, VEGFAVEGFR-2 signaling pathway, naba secreted factors, Class A 1 Rhodopsin-Like Receptors, PI3K-Akt signaling pathway, and Focal Adhesion-PI3K-Akt-mTOR-signaling pathway were differentially enriched in PAXIP1-AS1 high expression phenotype. PAXIP1-AS1 was significantly downregulated in OC cell lines compared with IOSE29 cell line. The expression of PAXIP1-AS1 was associated with immune infiltration. low expression of PAXIP1-AS1 was correlated with poor OS (HR: 0.52; 95% CI: 0.34–0.80; P = 0.003) from GSE138866. There were some genomic variations between the PAXIP1-AS1 high and low expression groups. Low expression of PAXIP1-AS1 was significantly associated with poor survival and immune infiltration in OC. PAXIP1-AS1 could be a promising prognosis biomarker and response to immunotherapy for OC.