Laboratory of Cancer Genetics, Faculty of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil.
Department of Anesthesiology, Oncology and Radiology, Faculty of Medical Sciences, University of Campinas, Rua Alexander Fleming, 181, Cidade Universitária "Zeferino Vaz", Barão Geraldo, Campinas, São Paulo, CEP: 13083-970, Brazil.
Sci Rep. 2023 Oct 5;13(1):16762. doi: 10.1038/s41598-023-44040-7.
Advanced head and neck squamous cell carcinoma (HNSCC) patients have been treated with cisplatin (CDDP) chemoradiation, and the variability of treatment effects has been attributed to single nucleotide variants (SNVs) in genes of metabolic pathways. This study investigated the roles of GSTM1, GSTT1, GSTP1 c.313A>G, XPC c.2815A>C, XPD c.934G>A and c.2251A>C, XPF c.2505T>C, ERCC1 c.354C>T, MLH1 c.93G>A, MSH2 c.211+9C>G, MSH3 c.3133G>A, EXO1 c.1765G>A, TP53 c.215G>C, CASP3 c.-1191A>G and c.-182-247G>T, FAS c.-1378G>A and c.-671A>G and FASL c.-844C>T SNVs in outcome of 109 patients treated with CDDP chemoradiation. Genotypes were identified in genomic DNA by PCR-based methods. Conventional criteria and tests analyzed response and survival. Patients with XPC c.2815AC or CC had 3.43 times more chances of presenting partial response or stable disease. Patients with FAS c.-671GG, GSTM1 present plus XPC c.2815AA, or plus XPD c.934GG, or plus XPD c.2251AA, or plus TP53 c.215GC or CC, and XPD c.2251AA plus XPF c.2505TT had up to 2.70 and 2.37 times more chances of presenting tumor progression and evolving to death, respectively. Our data indicate, for the first time, preliminary evidence that combined SNVs of CDDP metabolism act as independent prognostic factors and can be used to select patients for distinct treatments.
晚期头颈部鳞状细胞癌（HNSCC）患者已接受顺铂（CDDP）放化疗治疗，治疗效果的差异归因于代谢途径基因中的单核苷酸变异（SNVs）。本研究调查了 GSTM1、GSTT1、GSTP1 c.313A>G、XPC c.2815A>C、XPD c.934G>A 和 c.2251A>C、XPF c.2505T>C、ERCC1 c.354C>T、MLH1 c.93G>A、MSH2 c.211+9C>G、MSH3 c.3133G>A、EXO1 c.1765G>A、TP53 c.215G>C、CASP3 c.-1191A>G 和 c.-182-247G>T、FAS c.-1378G>A 和 c.-671A>G 和 FASL c.-844C>T 在 109 例接受 CDDP 放化疗治疗的患者的治疗结果中的作用。通过基于 PCR 的方法在基因组 DNA 中鉴定基因型。常规标准和测试分析了反应和生存。XPC c.2815AC 或 CC 的患者有 3.43 倍的机会出现部分缓解或稳定疾病。FAS c.-671GG、GSTM1 存在加 XPC c.2815AA，或加 XPD c.934GG，或加 XPD c.2251AA，或加 TP53 c.215GC 或 CC，以及 XPD c.2251AA 加 XPF c.2505TT 的患者，分别有高达 2.70 和 2.37 倍的机会出现肿瘤进展并死亡。我们的数据首次提供了初步证据，表明 CDDP 代谢的联合 SNVs 作为独立的预后因素，可以用于选择不同治疗方法的患者。
