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Open AccessFeature PaperArticle

Comprehensive Profiling of Genomic and Transcriptomic Differences between Risk Groups of Lung Adenocarcinoma and Lung Squamous Cell Carcinoma

1
Department of Molecular Biology and Genetics, Muğla Sıtkı Koçman University, 48000 Muğla, Turkey
2
Department of Bioinformatics, Muğla Sıtkı Koçman University, 48000 Muğla, Turkey
3
Department of Computer Engineering, Muğla Sıtkı Koçman University, 48000 Muğla, Turkey
*
Author to whom correspondence should be addressed.
Academic Editor: Raghu Sinha
J. Pers. Med. 2021, 11(2), 154; https://doi.org/10.3390/jpm11020154
Received: 30 December 2020 / Revised: 11 February 2021 / Accepted: 19 February 2021 / Published: 23 February 2021
(This article belongs to the Special Issue Recent Developments in Cancer Systems Biology)
Lung cancer is the second most frequently diagnosed cancer type and responsible for the highest number of cancer deaths worldwide. Lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) are subtypes of non-small-cell lung cancer which has the highest frequency of lung cancer cases. We aimed to analyze genomic and transcriptomic variations including simple nucleotide variations (SNVs), copy number variations (CNVs) and differential expressed genes (DEGs) in order to find key genes and pathways for diagnostic and prognostic prediction for lung adenocarcinoma and lung squamous cell carcinoma. We performed a univariate Cox model and then lasso-regularized Cox model with leave-one-out cross-validation using The Cancer Genome Atlas (TCGA) gene expression data in tumor samples. We generated 35- and 33-gene signatures for prognostic risk prediction based on the overall survival time of the patients with LUAD and LUSC, respectively. When we clustered patients into high- and low-risk groups, the survival analysis showed highly significant results with high prediction power for both training and test datasets. Then, we characterized the differences including significant SNVs, CNVs, DEGs, active subnetworks, and the pathways. We described the results for the risk groups and cancer subtypes separately to identify specific genomic alterations between both high-risk groups and cancer subtypes. Both LUAD and LUSC high-risk groups have more downregulated immune pathways and upregulated metabolic pathways. On the other hand, low-risk groups have both up- and downregulated genes on cancer-related pathways. Both LUAD and LUSC have important gene alterations such as CDKN2A and CDKN2B deletions with different frequencies. SOX2 amplification occurs in LUSC and PSMD4 amplification in LUAD. EGFR and KRAS mutations are mutually exclusive in LUAD samples. EGFR, MGA, SMARCA4, ATM, RBM10, and KDM5C genes are mutated only in LUAD but not in LUSC. CDKN2A, PTEN, and HRAS genes are mutated only in LUSC samples. The low-risk groups of both LUAD and LUSC tend to have a higher number of SNVs, CNVs, and DEGs. The signature genes and altered genes have the potential to be used as diagnostic and prognostic biomarkers for personalized oncology. View Full-Text
Keywords: TCGA; non-small-cell lung cancer; lung adenocarcinoma (LUAD); lung squamous cell carcinoma (LUSC); differential expression; SNV; CNV; risk group; signature; survival TCGA; non-small-cell lung cancer; lung adenocarcinoma (LUAD); lung squamous cell carcinoma (LUSC); differential expression; SNV; CNV; risk group; signature; survival
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MDPI and ACS Style

Zengin, T.; Önal-Süzek, T. Comprehensive Profiling of Genomic and Transcriptomic Differences between Risk Groups of Lung Adenocarcinoma and Lung Squamous Cell Carcinoma. J. Pers. Med. 2021, 11, 154. https://doi.org/10.3390/jpm11020154

AMA Style

Zengin T, Önal-Süzek T. Comprehensive Profiling of Genomic and Transcriptomic Differences between Risk Groups of Lung Adenocarcinoma and Lung Squamous Cell Carcinoma. Journal of Personalized Medicine. 2021; 11(2):154. https://doi.org/10.3390/jpm11020154

Chicago/Turabian Style

Zengin, Talip; Önal-Süzek, Tuğba. 2021. "Comprehensive Profiling of Genomic and Transcriptomic Differences between Risk Groups of Lung Adenocarcinoma and Lung Squamous Cell Carcinoma" J. Pers. Med. 11, no. 2: 154. https://doi.org/10.3390/jpm11020154

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