B细胞是肿瘤微环境中的适应性免疫细胞，在肿瘤的发生发展和转移中发挥着重要作用。然而，免疫 B 细胞相关基因的遗传变异在非小细胞肺癌 (NSCLC) 患者生存中的作用仍不清楚。在本研究中，我们首先评估了来自前列腺癌、肺癌、结直肠癌和卵巢癌 (PLCO) 癌症筛查的 1,185 名患者的发现数据集中的 220 个免疫 B 细胞相关基因中的 10,776 个单核苷酸多态性 (SNP) 与 NSCLC 生存之间的关联审判。我们在多变量 Cox 比例风险回归分析中发现 369 个 SNP 与 NSCLC 的总生存率 (OS) 显着相关（P ≤ 0.05，贝叶斯错误发现概率 ≤ 0.80），其中 18 个 SNP 在另一个包含 984 名患者的独立基因分型数据集中得到了验证来自哈佛肺癌易感性 (HLCS) 研究。然后，我们进行连锁不平衡 (LD) 分析，然后使用多变量 Cox 回归模型进行逐步分析。最后，两个独立的 SNP，肌醇多磷酸 5-磷酸酶 D (INPP5D) rs13385922 C>T 和外泌体成分 3 (EXOSC3) rs3208406 A>G，仍然与 NSCLC OS 显着相关，组合风险比 (HR) 为 1.14 (95%)置信区间 = 1.06-1.23，P = 2.41×10-4) 和 1.20 (95% 置信区间 = 1.14-1.28，P = 3.41×10-9)。此外，PLCO 数据集中，具有这两个 SNP 不利基因型组合的 NSCLC 患者与较差的 OS（P 趋势 = 0.0002）和疾病特异性生存（DSS，P 趋势 < 0.0001）相关。表达数量性状位点（eQTL）分析表明，INPP5D rs6782875 T等位基因与正常肺组织和全血样本中INPP5D mRNA表达水平升高显着相关，而EXOSC3 rs3208406 G等位基因与正常肺组织和全血样本中EXOSC3 mRNA表达水平升高显着相关。肺组织。我们的数据表明，这些免疫 B 细胞相关基因的遗传变异可能通过影响基因表达来预测 NSCLC 的生存。版权所有 © 2024 Lu、Liu、Wang、Tang、Luo、Du、Christiani 和 Wei。

B cells are adaptive immune cells in the tumor microenvironment and play an important role in tumor development and metastasis. However, the roles of genetic variants of the immunity B cell-related genes in the survival of patients with non-small cell lung cancer (NSCLC) remain unknown. In the present study, we first evaluated associations between 10,776 single nucleotide polymorphisms (SNPs) in 220 immunity B cell-related genes and survival of NSCLC in a discovery dataset of 1,185 patients from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. We found that 369 SNPs were significantly associated with overall survival (OS) of NSCLC in multivariable Cox proportional hazards regression analysis (P ≤ 0.05, Bayesian false discovery probability ≤ 0.80), of which 18 SNPs were validated in another independent genotyping dataset of 984 patients from the Harvard Lung Cancer Susceptibility (HLCS) Study. We then performed linkage disequilibrium (LD) analysis, followed by stepwise analysis with a multivariable Cox regression model. Finally, two independent SNPs, inositol polyphosphate-5-phosphatase D (INPP5D) rs13385922 C>T and exosome component 3 (EXOSC3) rs3208406 A>G, remained significantly associated withNSCLC OS with a combined hazards ratio (HR) of 1.14 (95% confidence interval = 1.06-1.23, P = 2.41×10-4) and 1.20 (95% confidence interval = 1.14-1.28, P = 3.41×10-9), respectively. Furthermore, NSCLC patients with the combination of unfavorable genotypes for these two SNPs were associated with a poor OS (P trend = 0.0002) and disease-specific survival (DSS, P trend < 0.0001) in the PLCO dataset. Expression quantitative trait loci (eQTL) analysis suggested that the INPP5D rs6782875 T allele was significantly correlated with elevated INPP5D mRNA expression levels in normal lung tissues and whole blood samples, while the EXOSC3 rs3208406 G allele was significantly correlated with increased EXOSC3 mRNA expression levels in normal lung tissues. Our data indicated that genetic variants in these immunity B cell-related genes may predict NSCLC survival possibly by influencing the gene expression.Copyright © 2024 Lu, Liu, Wang, Tang, Luo, Du, Christiani and Wei.