Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, Tex.
Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Tex.
J Thorac Cardiovasc Surg. 2018 Jun;155(6):2635-2645.e15. doi: 10.1016/j.jtcvs.2018.02.015. Epub 2018 Feb 15.
The purpose of this study was to explore the role of single nucleotide polymorphisms (SNPs) in cytokine signaling genes and to compare them with clinical outcomes in surgical patients with non-small cell lung cancer (NSCLC).
SNPs of the cytokine signaling pathway were analyzed using peripheral blood of 722 patients who underwent resection of stage I to III NSCLC between 1995 and 2009. Cox proportional hazard analyses were performed to identify SNPs associated with overall survival (OS) and risk of recurrence. Internal validation using bootstrap analysis selected SNPs for unfavorable genotype and survival tree analysis.
Seventeen and 9 SNPs were independently associated with OS and recurrence, respectively. Patients with ≥9 unfavorable genotypes experienced worse OS (median, 41 months) than patients with 7 to 8 (89 months) and ≤6 (153 months) after median follow-up of 71 months (P = 2.86 × 10). Patients with ≤3 unfavorable genotypes had greater time to recurrence (median not reached) than those with 4 to 6 (114 months) and ≥7 (44 months; P = 1.3 × 10). Survival tree analysis classified patients into 3 risk groups. Patients in the intermediate- (median OS, 82 months) and high-risk groups (43 months) had worse survival than the low-risk group (176 months; P = 5.51 × 10). Median time to recurrence was worse in the intermediate- (114 months) and high-risk groups (58 months) than the low-risk group (median not reached; P = 2.52 × 10).
Genetic variants in cytokine signaling pathways were associated with clinical outcomes in NSCLC patients treated with surgery individually and cumulatively. Further studies are necessary to elucidate our findings and translate them into the clinical setting.
本研究旨在探讨细胞因子信号通路中单核苷酸多态性（SNPs）的作用，并将其与接受手术治疗的非小细胞肺癌（NSCLC）患者的临床结局进行比较。
分析了 1995 年至 2009 年间接受 I 期至 III 期 NSCLC 切除术的 722 例患者外周血中的 SNPs。采用 Cox 比例风险分析鉴定与总生存期（OS）和复发风险相关的 SNPs。采用 bootstrap 分析进行内部验证，选择不良基因型和生存树分析的 SNPs。
17 个和 9 个 SNPs 分别与 OS 和复发独立相关。在中位随访 71 个月后，≥9 个不良基因型的患者 OS 更差（中位，41 个月），而 7-8 个（89 个月）和≤6 个（153 个月）的患者 OS 更差（P=2.86×10）。≤3 个不良基因型的患者复发时间更长（中位未达到），而 4-6 个（114 个月）和≥7 个（44 个月）的患者复发时间更短（P=1.3×10）。生存树分析将患者分为 3 个风险组。中危组（中位 OS，82 个月）和高危组（43 个月）的患者 OS 比低危组（176 个月）差（P=5.51×10）。中危组（114 个月）和高危组（58 个月）的患者复发时间比低危组（中位未达到）差（P=2.52×10）。
细胞因子信号通路中的遗传变异与接受手术治疗的 NSCLC 患者的临床结局具有相关性。需要进一步的研究来阐明我们的发现，并将其转化为临床实践。
