Associations of TIMP-3 Genetic Polymorphisms with EGFR Statuses and Cancer Clinicopathologic Development in Lung Adenocarcinoma Patients

doi:10.3390/ijms21218023

中山醫學大學機構典藏 CSMUIR > 中山醫學大學研究成果 > 期刊論文 > Item 310902500/24827

Please use this identifier to cite or link to this item: https://ir.csmu.edu.tw:8080/ir/handle/310902500/24827

Title:	Associations of TIMP-3 Genetic Polymorphisms with EGFR Statuses and Cancer Clinicopathologic Development in Lung Adenocarcinoma Patients
Authors:	Chang, JH;Lai, TC;Yang, PJ;Shih, PC;Yang, YC;Lee, KL;Liu, TC;Tsao, TCY;Yang, SF;Chien, MH
Keywords:	tissue inhibitor of metalloproteinases-3;polymorphism;epidermal growth factor receptor;mutation;lung adenocarcinoma
Date:	2020
Issue Date:	2022-08-09T08:08:38Z (UTC)
Publisher:	MDPI
Abstract:	Lung adenocarcinoma (LADC) is a major subtype of lung cancer, particularly among populations of East Asia. The epidermal growth factor receptor (EGFR) is the most frequently mutated oncogene promoting LADC progression and can serve as a therapeutic target in LADC. The tissue inhibitor of metalloproteinases (TIMP)-3 is a major regulator of extracellular matrix turnover via targeting of matrix metalloproteinases (MMPs), and thus, plays a critical role in tumor development and progression. The purpose of this study was to investigate potential associations among TIMP-3 genetic polymorphisms, EGFR statuses, and cancer clinicopathologic development in patients with LADC. In this study, 277 LADC patients with different EGFR statuses were recruited to dissect the allelic discrimination of TIMP-3 -1296 T>C (rs9619311), TIMP3 249T>C (rs9862), and TIMP3 261C>T (rs11547635) polymorphisms using a TaqMan allelic discrimination assay. Our data showed that compared to those LADC patients with wild-type CC homozygotes of TIMP-3 rs9862, patients harboring TT homozygotes of rs9862 were at a higher risk of developing mutant EGFR (adjusted odds ratio (AOR) = 2.530; 95% confidence interval (CI): 1.230-5.205; p = 0.012), particularly the EGFR L858R point mutation (AOR = 2.975; 95% CI: 1.182-7.488; p = 0.021). Moreover, we observed that TIMP-3 TT homozygotes of rs9862 were correlated with the incidence of EGFR mutations in patients with a smoking habit (p = 0.045). Within male patients harboring a mutant EGFR, TIMP-3 rs9862 T (CT+TT) allele carriers were at higher risk of developing an advanced stage (p = 0.025) and lymph node metastasis (p = 0.043). Further analyses of clinical datasets revealed correlations of TIMP-3 expression with a favorable prognosis in patients with LADC. In conclusion, the data suggest that TIMP-3 rs9862 polymorphisms may contribute to identify subgroups of lung cancer patients at high risk for tumor progression, among carriers of LADC-bearing mutant EGFR.
URI:	http://dx.doi.org/10.3390/ijms21218023 https://www.webofscience.com/wos/woscc/full-record/WOS:000588939800001 https://ir.csmu.edu.tw:8080/handle/310902500/24827
Relation:	INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES ,2020 ,v21 ,issue 21
Appears in Collections:	[中山醫學大學研究成果] 期刊論文

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