Jurisic Vladimir, Vukovic Vladimir, Obradovic Jasmina, Gulyaeva Lyudmila F, Kushlinskii Nikolay E, Djordjević Nataša
Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia.
Institute for Biomedicine, Eurac Research, Affiliated Institute of the University of Lübeck, Bolzano, Italy.
J Oncol. 2020 Mar 18;2020:1973241. doi: 10.1155/2020/1973241. eCollection 2020.
Tyrosine kinase inhibitor- (TKI-) based therapy revolutionized the overall survival and the quality of life in non-small-cell lung cancer (NSCLC) patients that have epidermal growth factor receptor () mutations. However, is a highly polymorphic and mutation-prone gene, with over 1200 single nucleotide polymorphisms (SNPs). Since the role of polymorphism on the treatment outcome is still a matter of debate, this research analyzed the available literature data, according to the PRISMA guidelines for meta-analyses. Research includes PubMed, Scopus, ISI Web of Science, and 14 of genome-wide association studies (GWAS) electronic databases in order to provide quantitative assessment of the association between ten investigated SNPs and the survival of NSCLC patients. The pooled HR and their 95% CI for OS and PFS for different polymorphisms using a random or fixed effect model based on the calculated heterogeneity between the studies was applied. The longest and the shortest median OSs were reported for the homozygous wild genotype and a variant allele carriers for rs712829 (-216G>T), respectively. Quantitative synthesis in our study shows that out of ten investigated SNPs (rs11543848, rs11568315, rs11977388, rs2075102, rs2227983, rs2293347, rs4947492, rs712829, rs712830, and rs7809028), only four, namely, rs712829 (-216G>T), rs11568315 (CA repeat), rs2293347 (D994D), and rs4947492, have been reported to affect the outcome of TKI-based NSCLC treatment. Of these, only -216G>T and variable CA repeat polymorphisms have been confirmed by meta-analysis of available data to significantly affect OS and PFS in gefitinib- or erlotinib-treated NSCLC patients.
基于酪氨酸激酶抑制剂（TKI）的疗法彻底改变了具有表皮生长因子受体（EGFR）突变的非小细胞肺癌（NSCLC）患者的总生存期和生活质量。然而，EGFR是一个高度多态且易于突变的基因，有超过1200个单核苷酸多态性（SNP）。由于EGFR多态性对治疗结果的作用仍存在争议，本研究根据PRISMA荟萃分析指南分析了现有文献数据。研究包括PubMed、Scopus、ISI科学网以及14个全基因组关联研究（GWAS）电子数据库，以便对十个研究的EGFR SNP与NSCLC患者生存率之间的关联进行定量评估。根据研究间计算出的异质性，使用随机或固定效应模型应用不同EGFR多态性的总生存风险比（HR）及其95%置信区间（CI）来评估总生存期（OS）和无进展生存期（PFS）。对于rs712829（-216G>T），纯合野生基因型和变异等位基因携带者分别报告了最长和最短的中位OS。我们研究中的定量综合分析表明，在十个研究的EGFR SNP（rs11543848、rs11568315、rs11977388、rs2075102、rs2227983、rs2293347、rs4947492、rs712829、rs712830和rs7809028）中，只有四个，即rs712829（-216G>T）、rs11568315（CA重复）、rs2293347（D994D）和rs4947492，据报道会影响基于TKI的NSCLC治疗结果。其中，只有-216G>T和可变CA重复多态性通过对现有数据的荟萃分析被证实会显著影响吉非替尼或厄洛替尼治疗的NSCLC患者的OS和PFS。
