Identification of MMP1 As a Potential Gene Conferring Erlotinib Resistance in Non-small Cell Lung Cancer Based on Bioinformatics Analyses

Overview

Journal Hereditas

Specialty Genetics

Date 2020 Jul 25

PMID 32703314

Citations 7

Authors

Huyue Zhou

Qiumei Xiang

Changpeng Hu

Jing Zhang

Qian Zhang

Rong Zhang

Affiliations

Soon will be listed here.

Abstract

Background: Non-small cell lung cancer (NSCLC) is the major type of lung cancer with high morbidity and poor prognosis. Erlotinib, an inhibitor of epidermal growth factor receptor (EGFR), has been clinically applied for NSCLC treatment. Nevertheless, the erlotinib acquired resistance of NSCLC occurs inevitably in recent years.

Methods: Through analyzing two microarray datasets, erlotinib resistant NSCLC cells microarray (GSE80344) and NSCLC tissue microarray (GSE19188), the differentially expressed genes (DEGs) were screened via R language. DEGs were then functionally annotated by Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, which up-regulated more than 2-folds in both datasets were further functionally analyzed by Oncomine, GeneMANIA, R2, Coremine, and FunRich.

Results: We found that matrix metalloproteinase 1 (MMP1) may confer the erlotinib therapeutic resistance in NSCLC. MMP1 highly expressed in erlotinib-resistant cells and NSCLC tissues, and it associated with poor overall survival. In addition, MMP1 may be associated with COPS5 and be involve in an increasing transcription factors HOXA9 and PBX1 in erlotinib resistance.

Conclusions: Generally, these results demonstrated that MMP1 may play a crucial role in erlotinib resistance in NSCLC, and MMP1 could be a prognostic biomarker for erlotinib treatment.

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References

Meza R, Meernik C, Jeon J, Cote M . Lung cancer incidence trends by gender, race and histology in the United States, 1973-2010. PLoS One. 2015; 10(3):e0121323. PMC: 4379166. DOI: 10.1371/journal.pone.0121323. View

Kosaka T, Yatabe Y, Endoh H, Yoshida K, Hida T, Tsuboi M . Analysis of epidermal growth factor receptor gene mutation in patients with non-small cell lung cancer and acquired resistance to gefitinib. Clin Cancer Res. 2006; 12(19):5764-9. DOI: 10.1158/1078-0432.CCR-06-0714. View

Cevenini A, Orru S, Mancini A, Alfieri A, Buono P, Imperlini E . Molecular Signatures of the Insulin-like Growth Factor 1-mediated Epithelial-Mesenchymal Transition in Breast, Lung and Gastric Cancers. Int J Mol Sci. 2018; 19(8). PMC: 6122069. DOI: 10.3390/ijms19082411. View

Lu Y, Lemon W, Liu P, Yi Y, Morrison C, Yang P . A gene expression signature predicts survival of patients with stage I non-small cell lung cancer. PLoS Med. 2006; 3(12):e467. PMC: 1716187. DOI: 10.1371/journal.pmed.0030467. View

Paez J, Janne P, Lee J, Tracy S, Greulich H, Gabriel S . EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science. 2004; 304(5676):1497-500. DOI: 10.1126/science.1099314. View

Mazor R, Alsaigh T, Shaked H, Altshuler A, Pocock E, Kistler E . Matrix metalloproteinase-1-mediated up-regulation of vascular endothelial growth factor-2 in endothelial cells. J Biol Chem. 2012; 288(1):598-607. PMC: 3537058. DOI: 10.1074/jbc.M112.417451. View

Goldstein D, Gray N, Zarrinkar P . High-throughput kinase profiling as a platform for drug discovery. Nat Rev Drug Discov. 2008; 7(5):391-7. DOI: 10.1038/nrd2541. View

Shepherd F, Pereira J, Ciuleanu T, Tan E, Hirsh V, Thongprasert S . Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med. 2005; 353(2):123-32. DOI: 10.1056/NEJMoa050753. View

Gammelgaard K, Vad-Nielsen J, Clement M, Weiss S, Daugaard T, Dagnaes-Hansen F . Up-Regulated FGFR1 Expression as a Mediator of Intrinsic TKI Resistance in EGFR-Mutated NSCLC. Transl Oncol. 2018; 12(3):432-440. PMC: 6297127. DOI: 10.1016/j.tranon.2018.11.017. View

10.

Shintani T, Higashisaka K, Maeda M, Hamada M, Tsuji R, Kurihara K . Eukaryotic translation initiation factor 3 subunit C is associated with acquired resistance to erlotinib in non-small cell lung cancer. Oncotarget. 2019; 9(101):37520-37533. PMC: 6331022. DOI: 10.18632/oncotarget.26494. View

11.

Ramalingam S, Owonikoko T, Khuri F . Lung cancer: New biological insights and recent therapeutic advances. CA Cancer J Clin. 2011; 61(2):91-112. DOI: 10.3322/caac.20102. View

12.

Levinson H, Sil A, Conwell J, Hopper J, Ehrlich H . Alpha V integrin prolongs collagenase production through Jun activation binding protein 1. Ann Plast Surg. 2004; 53(2):155-61. DOI: 10.1097/01.sap.0000112281.97409.a6. View

13.

Jakobsen K, Demuth C, Sorensen B, Nielsen A . The role of epithelial to mesenchymal transition in resistance to epidermal growth factor receptor tyrosine kinase inhibitors in non-small cell lung cancer. Transl Lung Cancer Res. 2016; 5(2):172-82. PMC: 4858579. DOI: 10.21037/tlcr.2016.04.07. View

14.

Zou W, Ma X, Yang H, Hua W, Chen B, Cai G . Hepatitis B X-interacting protein promotes cisplatin resistance and regulates CD147 via Sp1 in ovarian cancer. Exp Biol Med (Maywood). 2017; 242(5):497-504. PMC: 5367657. DOI: 10.1177/1535370216685007. View

15.

Longley D, Johnston P . Molecular mechanisms of drug resistance. J Pathol. 2005; 205(2):275-92. DOI: 10.1002/path.1706. View

16.

Witta S, Gemmill R, Hirsch F, Coldren C, Hedman K, Ravdel L . Restoring E-cadherin expression increases sensitivity to epidermal growth factor receptor inhibitors in lung cancer cell lines. Cancer Res. 2006; 66(2):944-50. DOI: 10.1158/0008-5472.CAN-05-1988. View

17.

Yang Z, Hackshaw A, Feng Q, Fu X, Zhang Y, Mao C . Comparison of gefitinib, erlotinib and afatinib in non-small cell lung cancer: A meta-analysis. Int J Cancer. 2017; 140(12):2805-2819. DOI: 10.1002/ijc.30691. View

18.

Pathan M, Keerthikumar S, Ang C, Gangoda L, Quek C, Williamson N . FunRich: An open access standalone functional enrichment and interaction network analysis tool. Proteomics. 2015; 15(15):2597-601. DOI: 10.1002/pmic.201400515. View

19.

Zhu C, da Cunha Santos G, Ding K, Sakurada A, Cutz J, Liu N . Role of KRAS and EGFR as biomarkers of response to erlotinib in National Cancer Institute of Canada Clinical Trials Group Study BR.21. J Clin Oncol. 2008; 26(26):4268-75. DOI: 10.1200/JCO.2007.14.8924. View

20.

Kapoor C, Vaidya S, Wadhwan V, Kaur G, Pathak A . Seesaw of matrix metalloproteinases (MMPs). J Cancer Res Ther. 2016; 12(1):28-35. DOI: 10.4103/0973-1482.157337. View