This study aimed to elucidate the impact of PTEN single nucleotide polymorphism (SNP) on clinical outcomes for advanced lung adenocarcinoma (LAC) patients treated with platinum-based chemotherapy. Three functional SNPs (rs11202607 G>A, rs701848 A>G, and rs11202592 G>C) of PTEN gene were genotyped by using DNA from blood samples of 618 advanced LAC patients, and their relationships with clinical outcomes were analyzed. The carriers of homozygous mutant of rs701848 and rs11202592 polymorphisms revealed significantly worse overall survival (OS) than those with heterozygote or wild-type homozygote (18.83 vs. 21.47 vs. 24.37 months, P = 0.034 and 13.40 vs. 19.03 vs. 21.90 months, P = 0.025, respectively). Subgroup analysis revealed that this association was particularly significant in tumor-lymph-node metastasis (TNM) stage III patients. The objective response rates (ORR) and disease control rates (DCR) of patients with genotype AA, AG, and GG in PTEN rs701848 polymorphism were statistically different (24.1 vs 16.6 vs 12.2 %, P = 0.017 and 82.7 vs 76.0 vs 70.2 %, P = 0.029, respectively). Haplotype analysis revealed a protective effect of the haplotype G-A-A (in the order of rs11202592, rs701848, and rs11202607) on chemotherapy efficacy and survival. Taken together, PTEN polymorphisms may contribute to survival and chemotherapy efficacy of advanced LAC patients treated with platinum-based agents.
Chemotherapy Lung adenocarcinoma PTENPlatinum Single nucleotide polymorphisms
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This study was supported by the National Natural Science Foundation of China (No. 81572269) and the Science and Technology Commission of Shanghai Municipality (No. 14411950800 and No. 134119a3400).
Compliance with ethical standards
All the subjects signed a consent form, and the study was approved by the ethics committee of Shanghai Pulmonary Hospital.
Pilkington G, Boland A, Brown T, Oyee J, Bagust A, Dickson R. A systematic review of the clinical effectiveness of first-line chemotherapy for adult patients with locally advanced or metastatic non-small cell lung cancer. Thorax. 2015;70:359–67.CrossRefPubMedGoogle Scholar
Lee Y, Yoon KA, Joo J, Lee D, Bae K, Han JY, et al. Prognostic implications of genetic variants in advanced non-small cell lung cancer: a genome-wide association study. Carcinogenesis. 2013;34:307–13.CrossRefPubMedGoogle Scholar
Giovannetti E, Toffalorio F, De Pas T, Peters GJ. Pharmacogenetics of conventional chemotherapy in non-small-cell lung cancer: a changing landscape? Pharmacogenomics. 2012;13:1073–86.CrossRefPubMedGoogle Scholar
Cao Q, Ju X, Li P, Meng X, Shao P, Cai H, et al. A functional variant in the MTOR promoter modulates its expression and is associated with renal cell cancer risk. PLoS One. 2012;7:e50302.CrossRefPubMedPubMedCentralGoogle Scholar
Xu X, Chen G, Wu L, Liu L. Association of genetic polymorphisms in PTEN and additional gene-gene interaction with risk of esophageal squamous cell carcinoma in Chinese Han population. Dis Esophagus. 2015. doi:10.1111/dote.12428.Google Scholar
Wang X, Lin Y, Lan F, Yu Y, Ouyang X, Wang X, et al. A GG allele of 3′-side AKT1 SNP is associated with decreased AKT1 activation and better prognosis of gastric cancer. J Cancer Res Clin Oncol. 2014;140:1399–411.CrossRefPubMedGoogle Scholar
Zhang X, Chen X, Zhai Y, Cui Y, Cao P, Zhang H, et al. Combined effects of genetic variants of the PTEN, AKT1, MDM2 and p53 genes on the risk of nasopharyngeal carcinoma. PLoS One. 2014;9:e92135.CrossRefPubMedPubMedCentralGoogle Scholar
Jing F, Mao Y, Zhang Z, Li Y, Cai S, Li Q, et al. The association of phosphatase and tensin homolog deleted on chromosome 10 polymorphisms and lifestyle habits with colorectal cancer risk in a Chinese population. Tumor Biol. 2014;35:9233–40.CrossRefGoogle Scholar
Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982;5:649–55.CrossRefPubMedGoogle Scholar
Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45:228–47.CrossRefPubMedGoogle Scholar
Barrett JC, Fry B, Maller J, Daly MJ. Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics. 2005;21:263–65.CrossRefPubMedGoogle Scholar
Milella M, Falcone I, Conciatori F, Cesta Incani U, Del Curatolo A, Inzerilli N, et al. PTEN: multiple functions in human malignant tumors. Fron Oncol. 2015;5:24.Google Scholar
Li J, Yen C, Liaw D, Podsypanina K, Bose S, Wang SI, et al. PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science. 1997;275:1943–7.CrossRefPubMedGoogle Scholar
Soria JC, Lee HY, Lee JI, Wang L, Issa JP, Kemp BL, et al. Lack of PTEN expression in non-small cell lung cancer could be related to promoter methylation. Clin Cancer Res. 2002;8:1178–84.PubMedGoogle Scholar
Lee S, Choi EJ, Jin C, Kim DH. Activation of PI3K/Akt pathway by PTEN reduction and PIK3CA mRNA amplification contributes to cisplatin resistance in an ovarian cancer cell line. Gynecol Oncol. 2005;97:26–34.CrossRefPubMedGoogle Scholar
Forgacs E, Biesterveld EJ, Sekido Y, Fong K, Muneer S, Wistuba II, et al. Mutation analysis of the PTEN/MMAC1 gene in lung cancer. Oncogene. 1998;17:1557–65.CrossRefPubMedGoogle Scholar
Marsit CJ, Zheng S, Aldape K, Hinds PW, Nelson HH, Wiencke JK, et al. PTEN expression in non-small-cell lung cancer: evaluating its relation to tumor characteristics, allelic loss, and epigenetic alteration. Hum Pathol. 2005;36:768–76.CrossRefPubMedGoogle Scholar