基因编码共抑制分子BTLA的变异与肾透明细胞癌患者治疗后的生存相关——前瞻性队列研究结果。
Variation in the gene encoding the co-inhibitory molecule BTLA is associated with survival in patients treated for clear cell renal carcinoma - results of a prospective cohort study.
发表日期：2023
作者：
Krzysztof Tupikowski, Anna Partyka, Edyta A Pawlak, Kuba Ptaszkowski, Romuald Zdrojowy, Irena Frydecka, Agnieszka Hałoń, Lidia Karabon
来源：
Cell Death & Disease
摘要：
免疫检查点阻断策略成功地应用于肾细胞癌（RCC）治疗，表明调节T细胞对RCC风险和进展的分子的重要性。在本研究中，我们评估了CTLA-4、BTLA和CD28基因的变异与RCC患者以及特别是透明细胞RCC（ccRCC）患者的总生存（OS）之间的关联。分析了以下单核苷酸多态性（SNP），先前使用RFLP方法或TaqMan SNP基因分型分析得到的结果：CTLA-4基因：c.49A>G（rs231775），g.319C>T（rs5742909），g.*6230G>A（CT60; rs3087243），g.*10223G>T（Jo31; rs11571302）；CD28基因：c.17+3T>C（rs3116496），c.-1042G>A（rs3181098）；BTLA基因：rs2705511，rs1982809，rs9288952，rs9288953，rs2705535和rs1844089。在长时间观察（6.5年）中，我们发现携带BTLA rs1844089 SNP的A等位基因，以及晚期疾病（分期 ≥ 3，肿瘤分级 > 3，肿瘤直径 ≥ 70 mm），是死亡的独立危险因子，可使死亡风险增加两倍以上（HR = 2.21，95% CI：1.28-3.83）。此外，携带此等位基因的患者的总生存期比纯合子（GG）患者短6个月（42.5 vs. 48.2个月）。我们的结果首次表明编码BTLA的基因内部的遗传变异与透明细胞肾细胞癌患者的总生存显著相关。
版权：©2021 Termedia & Banach。
The successful introduction of immune checkpoint blockade approaches to renal-cell carcinoma (RCC) treatment indicates the importance of molecules regulating the T cell response to RCC risk and progression.In this study, we evaluate the association of variations in the CTLA-4, BTLA and CD28 genes with overall survival (OS) of RCC patients and specifically clear cell RCC (ccRCC) patients. The following single nucleotide polymorphisms (SNPs) previously genotyped using the RFLP method or TaqMan SNP Genotyping Assays were analyzed: CTLA-4 gene: c.49A>G (rs231775), g.319C>T (rs5742909), g.*6230G>A (CT60; rs3087243), g.*10223G>T (Jo31; rs11571302); CD28 gene: c.17+3T>C (rs3116496), c.-1042G>A (rs3181098); BTLA gene: rs2705511, rs1982809, rs9288952, rs9288953, rs2705535 and rs1844089.During long term observation (6.5 years) we discovered that possessing the A allele at BTLA rs1844089 SNP, together with advanced disease (stage ≥ 3, tumor grade > 3, tumor diameter ≥ 70 mm), is an independent risk factor of death which increases the hazard ratio (HR) of death by more than two-fold (HR = 2.21, 95% CI: 1.28-3.83). Furthermore, the OS of patients bearing this allele is 6 months shorter than for homozygous (GG) patients (42.5 vs. 48.2 months).Our results indicate for the first time that genetic variation within the gene encoding BTLA is significantly associated with overall survival in clear cell renal cell carcinoma patients.Copyright: © 2021 Termedia & Banach.