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Lung cancer has high incidence and mortality rates, and lung squamous cell carcinoma (LUSC) is a common form of non-small-cell lung carcinoma (NSCLC). The aim of our study was to discover long non-coding RNAs (lncRNAs) associated with LUSC prognosis. RNA-sequencing data obtained from LUSC samples were extracted from The Cancer Genome Atlas database. Using the limma package, differentially expressed genes (DEGs; including differentially expressed lncRNA genes (DELs), coding genes (DECs), and other genes (DEOs)) between LUSC and control samples were analyzed. Using Kaplan-Meier survival analysis, prognosis-associated lncRNAs were further selected. Following the calculation of Pearson's correlation coefficients between DELs and other DEGs, the DEL-DEG co-expression network was visualized using Cytoscape software. Using the clusterProfiler package, potential functions for DECs co-expressed with DELs were predicted. There were 1,305 DEGs in LUSC samples, including 153 DELs, 1,109 DECs, and 43 DEOs. Based on survival analysis, 22 prognosis-associated lncRNAs (including surfactant associated 1, pseudogene (SFTA1P), long intergenic non-protein coding RNA 968 (LINC00968), GATA6 antisense RNA 1, (GATA6-AS1) TBX5 antisense RNA 1 (TBX5-AS1) and FEZF1 antisense RNA 1 (FEZF1-AS1)) in LUSC were selected from these DELs, and the associated abnormal expression levels were also verified in LUSC clinical samples. A DEL-DEG co-expression network was constructed, which involved 93 DELs. Co-expressed DECs were enriched for only 8 prognosis-associated DELs, including LINC00968, SFTA1P, and TBX5-AS1. Specifically, mitogen-activated protein kinase (MAPK) signaling pathway-associated genes were enriched in DECs co-expressed with LINC00968, SFTA1P, GATA6-AS1, TBX5-AS1 and FEZF1-AS1, which may be prognosis-associated lncRNAs in LUSC. In addition, LINC00968 may affect the outcome of patients with LUSC via the MAPK signaling pathway.

SFTA1P, LINC00968, GATA6‑AS1, TBX5‑AS1, and FEZF1‑AS1 are crucial long non‑coding RNAs associated with the prognosis of lung squamous cell carcinoma