开发和验证稳健的胃癌免疫相关预后标志物。

BACKGROUND: An increasing number of reports have found that immune-related genes (IRGs) have a significant impact on the prognosis of a variety of cancers, but the prognostic value of IRGs in gastric cancer (GC) has not been fully elucidated. METHODS: Univariate Cox regression analysis was adopted for the identification of prognostic IRGs in three independent cohorts (GSE62254, = 300; GSE15459, = 191; and GSE26901, = 109). After obtaining the intersecting prognostic genes, the three independent cohorts were merged into a training cohort ( = 600) to establish a prognostic model. The risk score was determined using multivariate Cox and LASSO regression analyses. Patients were classified into low-risk and high-risk groups according to the median risk score. The risk score performance was validated externally in the three independent cohorts (GSE26253, = 432; GSE84437, = 431; and TCGA, = 336). Immune cell infiltration (ICI) was quantified by the CIBERSORT method. RESULTS: A risk score comprising nine genes showed high accuracy for the prediction of the overall survival (OS) of patients with GC in the training cohort (AUC > 0.7). The risk of death was found to have a positive correlation with the risk score. The univariate and multivariate Cox regression analyses revealed that the risk score was an independent indicator of the prognosis of patients with GC ( < 0.001). External validation confirmed the universal applicability of the risk score. The low-risk group presented a lower infiltration level of M2 macrophages than the high-risk group ( < 0.001), and the prognosis of patients with GC with a higher infiltration level of M2 macrophages was poor ( = 0.011). According to clinical correlation analysis, compared with patients with the diffuse and mixed type of GC, those with the Lauren classification intestinal GC type had a significantly lower risk score ( = 0.00085). The patients' risk score increased with the progression of the clinicopathological stage. CONCLUSION: In this study, we constructed and validated a robust prognostic signature for GC, which may help improve the prognostic assessment system and treatment strategy for GC.

背景：越来越多的报告发现，免疫相关基因（IRGs）对多种癌症的预后有显著影响，但 IRGs 在胃癌（GC）中的预后价值尚未完全阐明。

方法：采用单因素 Cox 回归分析鉴定了三个独立队列（GSE62254，n=300；GSE15459，n=191；GSE26901，n=109）中的预后 IRGs。获得交集预后基因后，将三个独立队列合并为训练队列（n=600），建立预后模型。使用多因素 Cox 和 LASSO 回归分析确定风险评分。根据中位数风险评分将患者分为低风险组和高风险组。在三个独立队列（GSE26253，n=432；GSE84437，n=431；TCGA，n=336）中对风险评分进行外部验证。采用 CIBERSORT 方法量化免疫细胞浸润（ICI）。

结果：一个包含 9 个基因的风险评分在训练队列中对 GC 患者的总生存期（OS）预测具有较高的准确性（AUC>0.7）。死亡风险与风险评分呈正相关。单因素和多因素 Cox 回归分析表明，风险评分是 GC 患者预后的独立指标（<0.001）。外部验证证实了风险评分的普遍适用性。低风险组的 M2 巨噬细胞浸润水平低于高风险组（<0.001），M2 巨噬细胞浸润水平较高的 GC 患者预后较差（=0.011）。根据临床相关性分析，与弥漫型和混合型 GC 患者相比，Lauren 分类肠型 GC 患者的风险评分明显较低（=0.00085）。患者的风险评分随临床病理分期的进展而增加。

结论：本研究构建并验证了 GC 的稳健预后标志物，可能有助于改善 GC 的预后评估系统和治疗策略。