Geredeli Caglayan, Artac Mehmet, Yildirim Selman, Inal Ali, Dede Isa, Guler Tunc, Boruban Melih Cem, Koral Lokman, Karaagac Mustafa, Zamani Ayse Gul, Altinok Tamer, Aribas Olgun, Bozcuk Hakan, Demirkazik Ahmet
Department of Medical Oncology, Meram Medical Faculty, Necmettin Erbakan University, Meram, 42100, Konya, Turkey,
Tumour Biol. 2015 Jun;36(6):4279-85. doi: 10.1007/s13277-015-3066-2. Epub 2015 Jan 18.
Identification of biomarkers used for the prognostic evaluation of non-small cell lung cancer (NSCLC) patients is important. The aim of this study was to evaluate the potential prognostic value of XRCC1, ERCC1, ERCC2, and TP53 single nucleotide polymorphisms (SNPs) in completely resected NSCLC patients. In total, 130 patients, surgically treated for NSCLC between 2000 and 2012, were included. An analysis of SNPs from peripheral blood cells was performed by polymerase chain reaction. XRCC1 Arg399Gln, ERCC1 Asn118Asn, ERCC2 Lys751Gln, and TP53 Arg72Pro polymorphisms were evaluated in conjunction with clinical and pathological parameters and survival. Kaplan-Meier method and Cox regression analysis were used. Median age rate was 59.3, ranging between 36 and 78 years. Median relapse-free survival duration (RFS) was found as 46.2 months. In those with ERCC2 CC allele, median RFS was detected as 28.3 months (95 % confidence interval (CI), 20.8-35.8), 46.9 months in those with CT heterozygous (95 % CI, 18.6-75.2), and 80.1 months for those with TT mutant allel (95 % CI, 33.0-127.2). Median RFS was seen to be longer in mutant group and also statistically significant (P = 0.018). Additionally, upon evaluating CC normal group with CT + TT alleles including mutant alleles, median RFS was found as 56.5 months (95 % CI, 24.6-88.4) in CT + TT group, and this was statistically significant (P = 0.005) Also, median RFS was 15.1 months in those including ERCC2 CC allele and 56.5 months in CT + TT allele in the group with no adjuvant treatment (P = 0.001). In conclusion, our study showed that ERCC2/XPD polymorphism is an independent prognostic factor in operated NSCLC patients, and these findings should be supported with prospective studies.
鉴定用于非小细胞肺癌（NSCLC）患者预后评估的生物标志物很重要。本研究的目的是评估XRCC1、ERCC1、ERCC2和TP53单核苷酸多态性（SNP）在完全切除的NSCLC患者中的潜在预后价值。总共纳入了2000年至2012年间接受手术治疗的130例NSCLC患者。通过聚合酶链反应对外周血细胞的SNP进行分析。结合临床和病理参数及生存情况，评估XRCC1 Arg399Gln、ERCC1 Asn118Asn、ERCC2 Lys751Gln和TP53 Arg72Pro多态性。采用Kaplan-Meier法和Cox回归分析。中位年龄为59.3岁，范围在36至78岁之间。中位无复发生存期（RFS）为46.2个月。在携带ERCC2 CC等位基因的患者中，中位RFS为28.3个月（95%置信区间（CI），20.8 - 35.8）；在携带CT杂合子的患者中为46.9个月（95% CI，18.6 - 75.2）；在携带TT突变等位基因的患者中为80.1个月（95% CI，33.0 - 127.2）。突变组的中位RFS更长，且具有统计学意义（P = 0.018）。此外，在评估包含突变等位基因的CT + TT等位基因的CC正常组时，CT + TT组的中位RFS为56.5个月（95% CI，24.6 - 88.4），具有统计学意义（P = 0.005）。同样，在未接受辅助治疗的组中，携带ERCC2 CC等位基因的患者中位RFS为15.1个月，携带CT + TT等位基因的患者为56.5个月（P = 0.001）。总之，我们的研究表明，ERCC2/XPD多态性是接受手术的NSCLC患者的独立预后因素，这些发现应通过前瞻性研究加以证实。
