Abstract
Lung squamous cell carcinoma (LUSC) is a disease with high morbidity and mortality. Many studies have shown that aberrant alternative splicing (AS) can lead to tumorigenesis, and splicing factors (SFs) serve as an important function during AS. In this research, we propose an analysis method based on synergy to screen key factors that regulate the initiation and progression of LUSC. We first screened alternative splicing events (ASEs) associated with survival in LUSC patients by bivariate Cox regression analysis. Then an association network consisting of OS-ASEs, SFs, and their targeting relationship was constructed to identify key SFs. Finally, 10 key SFs were selected in terms of degree centrality. The validation on TCGA and cross-platform GEO datasets showed that some SFs were significantly differentially expressed in cancer and paracancer tissues, and some of them were associated with prognosis, indicating that our method is valid and accurate. It is expected that our method would be applied to a wide range of research fields and provide new insights in the future.
Highlights
Lung cancer is one of the most common malignant tumors, and about 85% of cases are non-small cell lung cancer (NSCLC) (Wang et al, 2019)
In order to identify potential mechanisms of OS-alternative splicing events (ASEs) in lung squamous cell carcinoma (LUSC), the survival-related genes were analyzed by Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, which were both done by DAVID (Huang et al, 2009)
LSM7 is a prognosis-related key gene and mediates autophagy in LUSC, with significant expression differences between tumor and normal tissues (Gatica et al, 2019; Li et al, 2020); C1QBP is involved in various cellular processes, including mRNA splicing, ribosome biosynthesis, protein synthesis in mitochondria, apoptosis, transcriptional regulation, and viral infection, and its expression correlated with the prognosis of patients with lung, breast, and colon tumors (Saha et al, 2019); THOC1 is down-regulated in lung cancer cell lines SPC-A1 and NCI-H1975, and its overexpression inhibits cell proliferation, induces G2/M cell cycle arrest, and promotes cell apoptosis (Wan et al, 2014)
Summary
Lung cancer is one of the most common malignant tumors, and about 85% of cases are non-small cell lung cancer (NSCLC) (Wang et al, 2019). NSCLC can be divided into lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD) (Cheng et al, 2019). In recent years, targeted therapies for specific genes have greatly improved the living conditions of patients with advanced LUAD. LUSC patients respond poorly to targeted therapies due to the lack of driver mutations, and the specific molecular mechanisms of LUSC pathogenesis and progression have not been systematically assessed. Further exploration of the molecular mechanisms underlying the development of LUSC is essential for the development of more effective therapeutic regimens
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