Integration of Gene Profile to Explore the Hub Genes of Lung Adenocarcinoma: A Quasi-experimental Study

Overview

Journal Medicine (Baltimore)

Specialty General Medicine

Date 2020 Oct 30

PMID 33120770

Citations 5

Authors

Peiyan Hua

Yan Zhang

Chengyan Jin

Guangxin Zhang

Bin Wang

Affiliations

Soon will be listed here.

Abstract

Background: Lung cancer is a leading cause of morbidity diseases worldwide, but the key mechanisms of lung cancer remain elusive. This study aims to integrate of GSE 118370 and GSE 32863 profile and identify the key genes and pathway involved in human lung adenocarcinoma.

Methods: R software (RStudio, Version info: R 3.2.3, Forrester, USA) were utilized to find the differentially expressed genes. All the differentially expressed genes were analyzed by gene ontology, kyoto encyclopedia of genes and genomes. Protein-protein interaction networks were constructed by STRING database and analyzed by Cytohubber and Module. The cancer genome atlas database was used to verification the expression of hub genes. Quantitative reverse transcription-PCR was used to verify the bio-information results.

Results: Sixty-four lung adenocarcinoma and 64 adjacent normal tissues were used for integration analysis. Five hundred ninety-nine co-expression genes were locked. Biological processes mainly enriched in angiogenesis. Cellular component focused on extracellular exosome and molecular function aimed on protein disulfide isomerase activity. Cytohubber analysis showed that GNG11, FPR2, P4HB, PIK3R1, CDC20, ADCY4, TIMP1, IL6, CXC chemokine ligand (CXCL)12, and GAS6 acted as the hub genes during lung adenocarcinoma. Module analysis presented Chemokine signaling pathway was a key pathway. Quantitative reverse transcription-PCR showed that the expression level of GNG11, FPR2, PIK3R1, ADCY4, IL6, CXCL12, and GAS6 were significantly decreased and P4HB, CDC20 and TIMP1 were increased in human adenocarcinoma tissues (P < .05). The cancer genome atlas online analysis showed GNG11 was not associated with survival.

Conclusions: This study firstly reported GNG11 acting as a hub gene in adenocarcinoma. GNG11 could be used as a biomarker for human adenocarcinoma. Chemokine signaling pathway might play important roles in lung adenocarcinoma.

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References

Selvaraj G, Kaliamurthi S, Kaushik A, Khan A, Wei Y, Cho W . Identification of target gene and prognostic evaluation for lung adenocarcinoma using gene expression meta-analysis, network analysis and neural network algorithms. J Biomed Inform. 2018; 86:120-134. DOI: 10.1016/j.jbi.2018.09.004. View

Song Y, Tan J, Gao X, Wang L . Integrated analysis reveals key genes with prognostic value in lung adenocarcinoma. Cancer Manag Res. 2018; 10:6097-6108. PMC: 6252781. DOI: 10.2147/CMAR.S168636. View

Wang Z, Wei Y, Zhang R, Su L, Gogarten S, Liu G . Multi-Omics Analysis Reveals a HIF Network and Hub Gene EPAS1 Associated with Lung Adenocarcinoma. EBioMedicine. 2018; 32:93-101. PMC: 6021270. DOI: 10.1016/j.ebiom.2018.05.024. View

Galligan J, Petersen D . The human protein disulfide isomerase gene family. Hum Genomics. 2012; 6:6. PMC: 3500226. DOI: 10.1186/1479-7364-6-6. View

Siegel R, Miller K, Jemal A . Cancer statistics, 2019. CA Cancer J Clin. 2019; 69(1):7-34. DOI: 10.3322/caac.21551. View

Raposo G, Stoorvogel W . Extracellular vesicles: exosomes, microvesicles, and friends. J Cell Biol. 2013; 200(4):373-83. PMC: 3575529. DOI: 10.1083/jcb.201211138. View

Hossain M, Sakemura R, Fujii M, Ayusawa D . G-protein gamma subunit GNG11 strongly regulates cellular senescence. Biochem Biophys Res Commun. 2006; 351(3):645-50. DOI: 10.1016/j.bbrc.2006.10.112. View

Srivastava A, Filant J, Moxley K, Sood A, McMeekin S, Ramesh R . Exosomes: a role for naturally occurring nanovesicles in cancer growth, diagnosis and treatment. Curr Gene Ther. 2014; 15(2):182-92. DOI: 10.2174/1566523214666141224100612. View

Lovat P, Corazzari M, Armstrong J, Martin S, Pagliarini V, Hill D . Increasing melanoma cell death using inhibitors of protein disulfide isomerases to abrogate survival responses to endoplasmic reticulum stress. Cancer Res. 2008; 68(13):5363-9. PMC: 2917766. DOI: 10.1158/0008-5472.CAN-08-0035. View

10.

Piperdi B, Merla A, Perez-Soler R . Targeting angiogenesis in squamous non-small cell lung cancer. Drugs. 2014; 74(4):403-13. PMC: 4014113. DOI: 10.1007/s40265-014-0182-z. View

11.

Travis W, Brambilla E, Nicholson A, Yatabe Y, Austin J, Beasley M . The 2015 World Health Organization Classification of Lung Tumors: Impact of Genetic, Clinical and Radiologic Advances Since the 2004 Classification. J Thorac Oncol. 2015; 10(9):1243-1260. DOI: 10.1097/JTO.0000000000000630. View

12.

Nichols L, Saunders R, Knollmann F . Causes of death of patients with lung cancer. Arch Pathol Lab Med. 2012; 136(12):1552-7. DOI: 10.5858/arpa.2011-0521-OA. View

13.

Liang K, Liu Y, Eer D, Liu J, Yang F, Hu K . High CXC Chemokine Ligand 16 (CXCL16) Expression Promotes Proliferation and Metastasis of Lung Cancer via Regulating the NF-κB Pathway. Med Sci Monit. 2018; 24:405-411. PMC: 5788242. DOI: 10.12659/msm.906230. View

14.

Zhang X, Hu Z, Meng A, Duan G, Zhao Q, Yang J . Role of CCL20/CCR6 and the ERK signaling pathway in lung adenocarcinoma. Oncol Lett. 2017; 14(6):8183-8189. PMC: 5727607. DOI: 10.3892/ol.2017.7253. View

15.

Shi K, Li N, Yang M, Li W . Identification of Key Genes and Pathways in Female Lung Cancer Patients Who Never Smoked by a Bioinformatics Analysis. J Cancer. 2019; 10(1):51-60. PMC: 6329865. DOI: 10.7150/jca.26908. View

16.

Santana-Codina N, Carretero R, Sanz-Pamplona R, Cabrera T, Guney E, Oliva B . A transcriptome-proteome integrated network identifies endoplasmic reticulum thiol oxidoreductase (ERp57) as a hub that mediates bone metastasis. Mol Cell Proteomics. 2013; 12(8):2111-25. PMC: 3734573. DOI: 10.1074/mcp.M112.022772. View

17.

Gniadek T, Li Q, Tully E, Chatterjee S, Nimmagadda S, Gabrielson E . Heterogeneous expression of PD-L1 in pulmonary squamous cell carcinoma and adenocarcinoma: implications for assessment by small biopsy. Mod Pathol. 2017; 30(4):530-538. DOI: 10.1038/modpathol.2016.213. View

18.

Lastwika K, Wilson 3rd W, Li Q, Norris J, Xu H, Ghazarian S . Control of PD-L1 Expression by Oncogenic Activation of the AKT-mTOR Pathway in Non-Small Cell Lung Cancer. Cancer Res. 2015; 76(2):227-38. DOI: 10.1158/0008-5472.CAN-14-3362. View

19.

Shi L, Zhang B, Sun X, Zhang X, Lv S, Li H . CC chemokine ligand 18(CCL18) promotes migration and invasion of lung cancer cells by binding to Nir1 through Nir1-ELMO1/DOC180 signaling pathway. Mol Carcinog. 2016; 55(12):2051-2062. DOI: 10.1002/mc.22450. View

20.

Gautier L, Cope L, Bolstad B, Irizarry R . affy--analysis of Affymetrix GeneChip data at the probe level. Bioinformatics. 2004; 20(3):307-15. DOI: 10.1093/bioinformatics/btg405. View