Bioinformatics analysis identifies key genes of prognostic value in lung cancer
1Department of Medical Oncology, Xuzhou Central Hospital, 221009 Xuzhou, Jiangsu, China
DOI: 10.22514/jomh.2023.064 Vol.19,Issue 7,July 2023 pp.119-130
Submitted: 23 April 2023 Accepted: 18 May 2023
Published: 30 July 2023
Lung cancer is the most common human malignancy worldwide and can be divided into different types of carcinomas depending on their pathological features. Advances in medical science and technology have led to the identification of some lung cancer-related marker genes, including EGFR (epidermal growth factor receptor), BRAF (B-Raf proto-oncogene), RAS (RAS proto-oncogene, GTPase) and HER2 (human epidermal growth factor receptor 2). However, the underlying biomarker and key genes associated with different types of lung cancer are still poorly understood. In this study, we analyzed a GEO (Gene Expression Omnibus) dataset and identified 28 upregulated intersection DEGs (different expression genes) and 125 downregulated intersection DEGs among AC (adenocarcinoma), PTC (primary typical carcinoid), PLCC (primary large cell carcinoma), PLCNC (primary large cell lung carcinoma) and PSCLC (primary small cell lung carcinoma). Through PPI (protein-protein interaction) network analysis, we identified 14 genes among the DEGs, namely MFAP4 (microfibril-associated protein 4), PDZD2 (PDZ domain containing 2), FBLN1 (fibulin 1), FBLN5 (fibulin 5), EFEMP1 (EGF containing fibulin extracellular matrix protein 1), KDR (kinase insert domain receptor), S1PR1 (sphingosine-1-phosphate receptor 1), CAV1 (caveolin 1), GRK5 (G protein-coupled receptor kinase 5), EDNRA (endothelin receptor type A), EDNRB (endothelin receptor type B), CALCRL (calcitonin receptor-like receptor), PTGER4 (prostaglandin E receptor 4), and ADRB1 (adrenoceptor beta 1), which were found to be downregulated in different subtypes of lung cancer and associated with poor survival outcomes. In addition, most of the screened DEGs demonstrated good predictive ability in LUAD (lung adenocarcinoma) and LUSC (lung squamous cell carcinoma). Among them, MFAP4 was found to promote cell proliferation while also suppressing cell migration and angiogenesis. In summary, we propose MFAP4, PDZD2, FBLN1, FBLN5, EFEMP1, KDR, S1PR1, CAV1, GRK5, EDNRA, EDNRB, CALCRL, PTGER4 and ADRB1 as potential prognostic markers in lung cancer patients.
Lung cancer; PPI analysis; GEO; TCGA; Key gene
Dan Song,Li Sun. Bioinformatics analysis identifies key genes of prognostic value in lung cancer. Journal of Men's Health. 2023. 19(7);119-130.
 Nicholson AG, Tsao MS, Beasley MB, Borczuk AC, Brambilla E, Cooper WA, et al. The 2021 WHO classification of lung tumors: impact of advances since 2015. Journal of Thoracic Oncology. 2022; 17: 362–387.
 Chaft JE, Shyr Y, Sepesi B, Forde PM. Preoperative and postoperative systemic therapy for operable non-small-cell lung cancer. Journal of Clinical Oncology. 2022; 40: 546–555.
 Wang L, Qu J, Liang Y, Zhao D, Rehman FU, Qin K, et al. Identification and validation of key genes with prognostic value in non‐small‐cell lung cancer via integrated bioinformatics analysis. Thoracic Cancer. 2020; 11: 851–866.
 Agapito G, Arbitrio M. Microarray data analysis protocol. Methods in Molecular Biology. 2022; 171: 263–271.
 Dong Y, Cao H, Liang Z. A curated target gene pool assisting early disease prediction and patient-specific treatment for small cell lung cancer. Journal of Computational Biology. 2018; 25: 576–585.
 Su C, Liu W, Wu L, Dong T, Liu J. Screening of hub gene targets for lung cancer via microarray data. Combinatorial Chemistry & High Throughput Screening. 2021; 24: 269–285.
 Zhang L, Chen J, Yang H, Pan C, Li H, Luo Y, et al. Multiple microarray analyses identify key genes associated with the development of non-small cell lung cancer from chronic obstructive pulmonary disease. Journal of Cancer. 2021; 12: 996–1010.
 Dong L, Yu L, Bai C, Liu L, Long H, Shi L, et al. USP27-mediated Cyclin E stabilization drives cell cycle progression and hepatocellular tumorigenesis. Oncogene. 2018; 37: 2702–2713.
 Sun M, Shao X, Wang Y. Microarray data analysis for transcriptome profiling. Methods in Molecular Biology. 2018; 270: 17–33.
 Larriba Y, Rueda C, Fernández MA, Peddada SD. Microarray data normalization and robust detection of rhythmic features. Methods in Molecular Biology. 2019; 99: 207–225.
 Dong L, Yu L, Li H, Shi L, Luo Z, Zhao H, et al. An NAD+-Dependent Deacetylase SIRT7 Promotes HCC development through deacetylation of USP39. IScience. 2020; 23: 101351.
 Yu L, Dong L, Wang Y, Liu L, Long H, Li H, et al. Reversible regulation of SATB1 ubiquitination by USP47 and SMURF2 mediates colon cancer cell proliferation and tumor progression. Cancer Letters. 2019; 448: 40–51.
 Kelley M, Fierstein S, Purkey L, DeCicco-Skinner K. Endothelial cell tube formation assay: an in vitro model for angiogenesis. Methods in Molecular Biology. 2022; 127: 187–196.
 Feng Y, Liu C, Xue Y, Chen Y, Wang Y, Wu X. MicroRNA-147b promotes lung adenocarcinoma cell aggressiveness through negatively regulating microfibril-associated glycoprotein 4 (MFAP4) and affects prognosis of lung adenocarcinoma patients. Gene. 2020; 730: 144316.
 Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians. 2021; 71: 209–249.
 Liu S, Zhang J, Zeng K, Wu Y. Perioperative targeted therapy for oncogene-driven NSCLC. Lung Cancer. 2022; 172: 160–169.
 Thai AA, Solomon BJ, Sequist LV, Gainor JF, Heist RS. Lung cancer. The Lancet. 2021; 398: 535–554.
 Cecchini MJ, Tarmey T, Ferreira A, Mangaonkar AA, Ferrer A, Patnaik MM, et al. Pathology, radiology, and genetics of interstitial lung disease in patients with shortened telomeres. American Journal of Surgical Pathology. 2021; 45: 871–884.
 Bu J, Zhang P, Zhu K, Yan Y, Shi B, Wang J, et al. Constructing a global transcriptional regulatory landscape for early non-small cell lung cancer to identify hub genes and key pathways. Aging. 2020; 12: 17948–17957.
 Zhang L, Chen J, Cheng T, Yang H, Li H, Pan C. Identification of the key genes and characterizations of tumor immune microenvironment in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). Journal of Cancer. 2020; 11: 4965–4979.
 Chen M, Liu X, Du J, Wang X, Xia L. Differentiated regulation of immune-response related genes between LUAD and LUSC subtypes of lung cancers. Oncotarget. 2017; 8: 133–144.
 Moin AT, Sarkar B, Ullah MA, Araf Y, Ahmed N, Rudra B. In silico assessment of EpCAM transcriptional expression and determination of the prognostic biomarker for human lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). Biochemistry and Biophysics Reports. 2021; 27: 101074.
 Fu L, Wang H, Wei D, Wang B, Zhang C, Zhu T, et al. The value of CEP55 gene as a diagnostic biomarker and independent prognostic factor in LUAD and LUSC. PLOS ONE. 2020; 15: e0233283.
 Chen S, Lu H, Chen G, Yang J, Huang W, Wang X, et al. Downregulation of miRNA-126-3p is associated with progression of and poor prognosis for lung squamous cell carcinoma. FEBS Open Bio. 2020; 10: 1624–1641.
 Wang Y, Shi M, Yang N, Zhou X, Xu L. GPR115 contributes to lung adenocarcinoma metastasis associated with LAMC2 and predicts a poor prognosis. Frontiers in Oncology. 2020; 10: 577530.
 Gao J, Qiu X, Xi G, Liu H, Zhang F, Lv T, et al. Downregulation of GSDMD attenuates tumor proliferation via the intrinsic mitochondrial apoptotic pathway and inhibition of EGFR/Akt signaling and predicts a good prognosis in nonsmall cell lung cancer. Oncology Reports. 2018; 40: 1971–84.
 Yang J, Song H, Chen L, Cao K, Zhang Y, Li Y, et al. Integrated analysis of microfibrillar-associated proteins reveals MFAP4 as a novel biomarker in human cancers. Epigenomics. 2019; 11: 1635–51.
 Han P, Yang H, Li X, Wu J, Wang P, Liu D, et al. Identification of a novel cancer stemness-associated ceRNA Axis in lung adenocarcinoma via stemness indices analysis. Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics. 2021; 28: 715–729.
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