Identification of plasminogen activator urokinase receptor-related non-coding RNA and immune prognostic signature for non-small cell lung cancer

Abstract

Objective  To explore the relevant regulation of Plasminogen Activator Urokinase Receptor (PLAUR) by non-coding RNAs (ncRNAs) and the relationship between PLAUR and immune cell infiltration and biomarkers.

Methods  This is a cross-sectional study. A total of 10 paired primary NSCLC tissues and adjacent noncancerous tissues were collected from Tianjin Medical University General Hospital for RT-qPCR. Clinical data were extracted for RNA sequencing expression data of the PLAUR gene. The authors performed PLAUR’s prognostic value analysis in NSCLC using The Cancer Genome Atlas (TCGA). The authors then identified ncRNAs contributing to PLAUR overexpression by combining analyses of expression, correlation, and survival. Kaplan-Meier curves and log-rank tests were used to evaluate Overall Survival (OS) and Disease-Free Survival (DFS) differences based on PLAUR expression levels. Finally, the relationship between PLAUR and immune cell infiltration, as well as immune cell biomarkers, was analyzed by immune cell infiltration analysis.

Results  Both the quantitative real-time polymerase chain reaction and the TCGA database results showed significant differences in the expression of PLAUR in NSCLC types. The results showed that patients with a high expression of PLAUR had poorer prognoses, and PLAUR can serve as a prognostic biomarker for patients with NSCLC. The results of studying the regulatory microRNAs (miRNAs) upstream of PLAUR indicated that hsa-miR-340-5p may be the most important regulatory miRNA of PLAUR in NSCLC. Further predictions for upstream long ncRNAs (lncRNAs) in hsa-miR-340-5p indicated that AC008555.6, AC026356.1, TRHDE-AS1, and SNHG14 were the upstream lncRNAs of the has-miR-340-5p/PLAUR axis with the most potential in NSCLC. The expression of PLAUR was significantly correlated with the expression of all immune cells in NSCLC.

Conclusion  Plasminogen activator urokinase receptor was differently expressed and positively correlated with an unfavorable prognosis in NSCLC. The MIRLET7BHG/hsa-miR-127-3p axis was identified as the most likely upstream ncRNA-related pathway for PLAUR in NSCLC. This study provides insights into the molecular mechanism of action of PLAUR in NSCLC, which may help to develop new drugs to regulate PLAUR expression or its function in tumor development and provide new targets for the treatment of NSCLC.