Background: Recent studies have shown that low-density lipoprotein receptor-related protein 1b (LRP1B), as a potential tumor suppressor, is implicated in the response to immunotherapy. The frequency of LRP1B mutation gene is high in many cancers, but its role in gastric cancer (GC) has not been determined. Methods: The prognostic value of LRP1B mutation in a cohort containing 100 patients having received radical gastrectomy for stage II–III GC was explored. By analyzing the data of LRP1B mRNA, the risk score of differentially expressed genes (DEGs) between LRP1B mutation-type and wild-type was constructed based on the TCGA-STAD cohort. The infiltration of tumor immune cells was evaluated by the CYBERSORT algorithm and verified by immunohistochemistry. Results: LRP1B gene mutation was an independent risk factor for disease-free survival (DFS) in GC patients (HR = 2.57, 95% CI: 1.28–5.14,p= 0.008). The Kaplan–Meier curve demonstrated a shorter survival time in high-risk patients stratified according to risk score (p< 0.0001). CYBERSORT analysis showed that the DEGs were mainly concentrated in CD4+T cells and macrophages. TIMER analysis suggested that LRP1B expression was associated with the infiltration of CD4+T cells and macrophages. Immunohistochemistry demonstrated that LRP1B was expressed in the tumor cells (TCs) and immune cells in 16/89 and 26/89 of the cohort, respectively. LRP1B-positive TCs were associated with higher levels of CD4+T cells, CD8+T cells, and CD86/CD163 (p< 0.05). Multivariate analysis showed that LRP1B-positive TCs represented an independent protective factor of DFS in GC patients (HR = 0.43, 95% CI: 0.10–0.93,p= 0.042). Conclusions: LRP1B has a high prognostic value in GC. LRP1B may stimulate tumor immune cell infiltration to provide GC patients with survival benefits.
背景：近期研究表明，低密度脂蛋白受体相关蛋白1b（LRP1B）作为潜在抑癌基因，与免疫治疗反应密切相关。该基因突变在多种癌症中发生频率较高，但其在胃癌中的作用尚未明确。方法：本研究通过分析100例接受根治性胃切除术的II-III期胃癌患者队列，探讨LRP1B突变的预后价值。基于TCGA-STAD队列中LRP1B突变型与野生型的差异表达基因（DEGs）数据构建风险评分模型，采用CYBERSORT算法评估肿瘤免疫细胞浸润情况，并通过免疫组化进行验证。结果：LRP1B基因突变是胃癌患者无病生存期（DFS）的独立危险因素（HR=2.57，95%CI：1.28-5.14，p=0.008）。Kaplan-Meier曲线显示按风险评分分层的高危患者生存时间显著缩短（p<0.0001）。CYBERSORT分析表明DEGs主要富集于CD4+T细胞和巨噬细胞。TIMER分析提示LRP1B表达与CD4+T细胞及巨噬细胞浸润相关。免疫组化显示队列中16/89例肿瘤细胞和26/89例免疫细胞存在LRP1B表达。LRP1B阳性肿瘤细胞与更高水平的CD4+T细胞、CD8+T细胞及CD86/CD163表达显著相关（p<0.05）。多因素分析表明LRP1B阳性肿瘤细胞是胃癌患者DFS的独立保护因素（HR=0.43，95%CI：0.10-0.93，p=0.042）。结论：LRP1B在胃癌中具有重要预后价值，可能通过促进肿瘤免疫细胞浸润为胃癌患者带来生存获益。
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