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Lung squamous cell carcinoma (LUSC) has a poor clinical prognosis and a lack of available targeted therapies. Therefore, there is an urgent need to identify novel prognostic markers and therapeutic targets to assist in the diagnosis and treatment of LUSC. With the development of high-throughput sequencing technology, integrated analysis of multi-omics data will provide annotation of pathogenic non-coding variants and the role of non-coding sequence variants in cancers. Here, we integrated RNA-seq profiles and copy number variation (CNV) data to study the effects of non-coding variations on gene regulatory network. Furthermore, the 372 long non-coding RNAs (lncRNA) regulated by CNV were used as candidate genes, which could be used as biomarkers for clinical application. Nine lncRNAs including  LINC00896 ,  MCM8-AS1 ,  LINC01251 ,  LNX1-AS1 ,  GPRC5D-AS1 ,  CTD-2350J17.1 ,  LINC01133 ,  LINC01121 , and  AC073130.1  were recognized as prognostic markers for LUSC. By exploring the association of the prognosis-related lncRNAs (pr-lncRNAs) with immune cell infiltration,  GPRC5D-AS1  and  LINC01133  were highlighted as markers of the immunosuppressive microenvironment. Additionally, the cascade response of pr-lncRNA-CNV-mRNA-physiological functions was revealed. Taken together, the identification of prognostic markers and carcinogenic regulatory mechanisms will contribute to the individualized treatment for LUSC and promote the development of precision medicine.

Characterizing the Copy Number Variation of Non-Coding RNAs Reveals Potential Therapeutic Targets and Prognostic Markers of LUSC