Integrated bioinformatics analyses identifying key transcriptomes correlated with prognosis and immune infiltrations in lung squamous cell carcinoma

Rana A Alghamdi; Maryam H Al-Zahrani

doi:10.1016/j.sjbs.2023.103596

Integrated bioinformatics analyses identifying key transcriptomes correlated with prognosis and immune infiltrations in lung squamous cell carcinoma

Saudi J Biol Sci. 2023 Apr;30(4):103596. doi: 10.1016/j.sjbs.2023.103596. Epub 2023 Feb 11.

Authors

Rana A Alghamdi¹, Maryam H Al-Zahrani²

Affiliations

¹ Department of Chemistry, Science and Arts College, King Abdulaziz University, Rabigh, Saudi Arabia.
² Biochemistry Department, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.

Abstract

Background: Lung Squamous Cell Carcinoma (LUSC) is a major subtype of lung malignancies and is associated with the cause of cancer-mediated mortality worldwide. However, identification of transcriptomic signatures associated with survival-prognosis and immunity of tumor remains lacking.

Method: The GSE2088, GSE6044, GSE19188, GSE21933, GSE33479, GSE33532, and GSE74706 were integrated for identifying differentially expressed genes (DEGs) with combined effect sizes. Also, the TCGA LUSC cohort was used for further analysis. A series of bioinformatics methods were utilized for conducting the whole study.

Results: The 831 genes (such as DSG3, PKP1, DSC3, TPX2, and UBE2C) were found upregulated and the 731 genes (such as ABCA8, SELENBP1, FAM107A, and CACNA2D2) were downregulated in the LUSC. The functional enrichment analysis identifies the upregulated KEGG pathways, including cell cycle, DNA replication, base excision repair, proteasome, mismatch repair, and cellular senescence. Also, the key hub genes (such as EGFR, HRAS, JUN, CDH1, BRCA1, CASP3, RHOA, HDAC1, HIF1A, and CCNA2) were identified along with the eight gene modules that were significantly related to the protein-protein interaction (PPI). The clinical analyses identified that the overexpression group of CDH3, PLAU, PKP3, STIL, CALU, LOXL2, POSTN, DPP3, GALNT2, LOX, and ITPA are substantially associated with a poor survival prognosis and the downregulated group of IL18R1 showed a similar trend. Moreover, our investigation demonstrated that the survival-associated genes were correlated with the stromal and immune scores in LUSC, indicating that the survival-associated genes regulate tumor immunity. The survival-associated genes were genetically altered in 27% of LUSC patients and showed excellent diagnostic efficiency. Finally, the consistent expression level of CDH3, PLAU, PKP3, STIL, CALU, LOXL2, POSTN, DPP3, GALNT2, and ITPA were found in the TCGA LUSC cohort.

Conclusions: The identification of key transcriptomic signatures can be elucidated by the crucial mechanism of LUSC carcinogenesis.

Keywords: Bioinformatics methods; Diagnostic efficiency; Hub genes; Lung Squamous Cell Carcinoma; Lung malignancies; Tumor immunity.