Identification of a 5-lncRNA-Based Signature for Immune Characteristics and Prognosis of Lung Squamous Cell Carcinoma and Verification of the Function of lncRNA SPATA41.

Abstract

Lung squamous cell carcinoma (LUSC) is one of the most lethal cancers worldwide. Traditional tumor-node-metastasis (TNM) staging system has many insufficiencies in predicting immune characteristics, overall survival (OS), and prognosis of LUSC. LncRNA is currently found involved in tumor development and effectively predicts tumor prognosis. We screened potential tumor-related lncRNAs for immune characteristics and constructed a nomogram combining lncRNA and traditional clinical indicators for prognosis prediction. We obtained the large-scale gene expression profiles of samples from 492 LUSC patients in The Cancer Genome Atlas database. SPATA41, AL034550.2, AP003721.2, AC106786.1, and AC078889.1 were finally screened to construct a 5-lncRNA-based signature. The risk score of the signature divided patients into subgroups of high-risk and low-risk with significant differences in OS. Their area under the curve (AUC) reached more than 0.70 in 1, 3, and 5 years. In addition, compared with the high-risk subgroup, the low-risk subgroup exhibited a remarkably favorable prognosis and TME score, along with a higher immune infiltration score and lower TIDE score. The signature also significantly related to chemotherapy response, especially in cisplatin, vinorelbine, and paclitaxel. Importantly, the nomogram we constructed had good reliability with the assessment of the calibration chart and consistency index (c-index). GO and KEGG enrichment analysis indicated that co-expression mRNAs of the 5 lncRNAs were mainly focused on RNA splicing, DNA replication, and protein serine/threonine kinase activity. Functional assays demonstrated that SPATA41, one of the five OS-related lncRNAs, regulated invasion, migration, proliferation, and programmed death in vitro. In summary, our 5-lncRNA-based signature has a good performance in predicting immune characteristics and prognosis of LUSC patients.