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

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 G...

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Main Authors: Rana A. Alghamdi, Maryam H. Al-Zahrani
Format: Article
Language:English
Published: Elsevier 2023-04-01
Series:Saudi Journal of Biological Sciences
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S1319562X23000414
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author Rana A. Alghamdi
Maryam H. Al-Zahrani
author_facet Rana A. Alghamdi
Maryam H. Al-Zahrani
author_sort Rana A. Alghamdi
collection DOAJ
description 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.
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spelling doaj.art-d7626397a0ce472199cf2398d7e93b0e2023-04-06T06:10:24ZengElsevierSaudi Journal of Biological Sciences1319-562X2023-04-01304103596Integrated bioinformatics analyses identifying key transcriptomes correlated with prognosis and immune infiltrations in lung squamous cell carcinomaRana A. Alghamdi0Maryam H. Al-Zahrani1Department of Chemistry, Science and Arts College, King Abdulaziz University, Rabigh, Saudi Arabia; Corresponding author at: Department of Chemistry, Science and Arts College, King Abdulaziz University, Rabigh, Saudi Arabia.Biochemistry Department, Faculty of Science, King Abdulaziz University, Jeddah, Saudi ArabiaBackground: 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.http://www.sciencedirect.com/science/article/pii/S1319562X23000414Lung malignanciesBioinformatics methodsHub genesTumor immunityDiagnostic efficiencyLung Squamous Cell Carcinoma
spellingShingle Rana A. Alghamdi
Maryam H. Al-Zahrani
Integrated bioinformatics analyses identifying key transcriptomes correlated with prognosis and immune infiltrations in lung squamous cell carcinoma
Saudi Journal of Biological Sciences
Lung malignancies
Bioinformatics methods
Hub genes
Tumor immunity
Diagnostic efficiency
Lung Squamous Cell Carcinoma
title Integrated bioinformatics analyses identifying key transcriptomes correlated with prognosis and immune infiltrations in lung squamous cell carcinoma
title_full Integrated bioinformatics analyses identifying key transcriptomes correlated with prognosis and immune infiltrations in lung squamous cell carcinoma
title_fullStr Integrated bioinformatics analyses identifying key transcriptomes correlated with prognosis and immune infiltrations in lung squamous cell carcinoma
title_full_unstemmed Integrated bioinformatics analyses identifying key transcriptomes correlated with prognosis and immune infiltrations in lung squamous cell carcinoma
title_short Integrated bioinformatics analyses identifying key transcriptomes correlated with prognosis and immune infiltrations in lung squamous cell carcinoma
title_sort integrated bioinformatics analyses identifying key transcriptomes correlated with prognosis and immune infiltrations in lung squamous cell carcinoma
topic Lung malignancies
Bioinformatics methods
Hub genes
Tumor immunity
Diagnostic efficiency
Lung Squamous Cell Carcinoma
url http://www.sciencedirect.com/science/article/pii/S1319562X23000414
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