Boldrin Elisa, Malacrida Sandro, Rumiato Enrica, Battaglia Giorgio, Ruol Alberto, Amadori Alberto, Saggioro Daniela
Immunology and Molecular Oncology, Veneto Institute of Oncology IOV-IRCCS, Padova, Italy.
Eurac Research, Institute of Mountain Emergency Medicine, Bolzano, Italy.
Front Oncol. 2019 Feb 21;9:85. doi: 10.3389/fonc.2019.00085. eCollection 2019.
Esophageal cancer (EC) is a very aggressive tumor, and no reliable prognostic markers exist especially for resectable advanced neoplasia. The principal aim of this study was to investigate the association of germline polymorphisms in nucleotide excision repair (NER) pathway genes with the overall survival (OS) of patients with advanced EC. As a second aim, we also studied the association of NER gene variants with response to cisplatin-based chemotherapy. Among the EC patients referred to our Institution between 2004 and 2012, we selected a cohort of 180 patients diagnosed with a clinical tumor stage ranging from IIB and IVA. Patients were genotyped for four NER variants, two in the (rs11615 and rs3212986) and two in the (rs1799793 and rs13181) genes. Kaplan-Meier analyses and Cox proportional hazards model were used to evaluate the associations of the selected variants with OS; association with response to neoadjuvant therapy was investigated using logistic regression. Results showed that the rs3212986 and the rs1799793 were significantly associated with shorter OS. On the contrary, response association analysis displayed that, while rs11615 and rs3212986 in were associated with response, both variants were not. By creating survival prediction models, we showed that the rs3212986 and the rs1799793 have a better predictability of the tumor stage alone. Furthermore, they were able to improve the power of the clinical model (AUC = 0.660 vs. AUC = 0.548, = 0.004). In conclusion, our results indicate that the rs3212986 and the rs1799793 could be used as surrogate markers for a better stratification of EC patients with advanced resectable tumor.
食管癌（EC）是一种侵袭性很强的肿瘤，尤其对于可切除的进展期肿瘤，不存在可靠的预后标志物。本研究的主要目的是调查核苷酸切除修复（NER）途径基因中的种系多态性与晚期EC患者总生存期（OS）之间的关联。作为第二个目的，我们还研究了NER基因变异与基于顺铂化疗反应之间的关联。在2004年至2012年间转诊至我院的EC患者中，我们选取了180例临床肿瘤分期为IIB至IVA期的患者组成队列。对患者进行了4种NER变异的基因分型，其中2种在 （rs11615和rs3212986）基因中，2种在 （rs1799793和rs13181）基因中。采用Kaplan-Meier分析和Cox比例风险模型评估所选变异与OS的关联；使用逻辑回归研究与新辅助治疗反应的关联。结果显示， 基因的rs3212986和 基因的rs1799793与较短的OS显著相关。相反，反应关联分析显示，虽然 基因中的rs11615和rs3212986与反应相关，但两个 基因的变异均不相关。通过创建生存预测模型，我们表明rs3212986和rs1799793单独对肿瘤分期具有更好的预测性。此外，它们能够提高临床模型的效能（AUC = 0.660对AUC = 0.548， = 0.004）。总之,我们的结果表明， 基因的rs3212986和 基因的rs1799793可作为更好地对晚期可切除肿瘤的EC患者进行分层的替代标志物。
