Department of Pathology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, China.
Digestive Endoscopic Center, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, China.
Pathol Oncol Res. 2022 Jul 19;28:1610479. doi: 10.3389/pore.2022.1610479. eCollection 2022.
PBRM1 gene abnormalities were recently found to play a role in tumor development and tumor immune activity. This article will explore the clinicopathological and molecular changes and tumor immune activity of the abnormal SWI/SNF complex subunit PBRM1 in gastric adenocarcinoma (GAC) and its significance. The cBioPortal, LinkedOmics and TISIDB datasets were used to analyze the abnormality of the PBRM1 gene in GAC and its relationship with prognosis, related molecular changes and tumor-infiltrating lymphocytes (TILs). In addition, 198 GAC cases were collected to further study the relationship between the loss/attenuation of PBRM1 expression and clinicopathology, prognosis, microsatellite stability, PD-L1 expression and TIL in GAC. DNA whole-exome sequencing was performed on 7 cases of gastric cancer with loss of PBRM1 expression. The cBioPortal data showed that PBRM1 deletion/mutation accounted for 7.32% of GAC and was significantly associated with several molecular changes, such as molecular subtypes of GAC. The LinkedOmics dataset showed that PBRM1 mutation and its promoter DNA methylation showed lower PBRM1 mRNA expression, and PBRM1 mutation cases showed significantly higher mRNA expression of PD-L1 (CD274). TISIDB data showed that PBRM1 abnormalities were significantly positively associated with multiple TILs. In our group of 198 cases, the loss/attenuation of PBRM1 expression was significantly positively correlated with intra-tumoral tumor infiltrating lymphocytes (iTILs) and deficient MMR and PD-L1 expression. Kaplan-Meier survival analysis showed that the overall survival of GAC patients with loss/attenuation of PBRM1 expression was significantly better ( = 0.023). iTIL was an independent prognostic factor of GAC. Loss of PBRM1 expression often co-occurs with mutations in other SWI/SNF complex subunit genes, and there are some repetitive KEGG signaling changes. Abnormality of the PBRM1 gene may be related to the occurrence of some GACs and can affect tumor immune activity, thereby affecting clinicopathology and prognosis. It may be a potentially effective predictive marker for immunotherapy and a novel therapeutic approach associated with synthetic lethality.
PBRM1 基因异常最近被发现与肿瘤的发生和肿瘤免疫活性有关。本文将探讨异常 SWI/SNF 复合物亚基 PBRM1 在胃腺癌 (GAC) 中的临床病理和分子变化及肿瘤免疫活性及其意义。使用 cBioPortal、LinkedOmics 和 TISIDB 数据集分析了 GAC 中 PBRM1 基因的异常及其与预后、相关分子变化和肿瘤浸润淋巴细胞 (TIL) 的关系。此外，收集了 198 例 GAC 病例，进一步研究了 PBRM1 表达缺失/减弱与 GAC 的临床病理、预后、微卫星不稳定性、PD-L1 表达和 TIL 的关系。对 7 例 PBRM1 表达缺失的胃癌进行了全外显子组测序。cBioPortal 数据显示，PBRM1 缺失/突变占 GAC 的 7.32%，与 GAC 的几种分子改变显著相关，如 GAC 的分子亚型。LinkedOmics 数据集显示，PBRM1 突变及其启动子 DNA 甲基化导致 PBRM1 mRNA 表达降低，而 PBRM1 突变病例的 PD-L1 (CD274)mRNA 表达显著升高。TISIDB 数据显示，PBRM1 异常与多种 TIL 显著正相关。在我们的 198 例病例中，PBRM1 表达缺失/减弱与肿瘤内肿瘤浸润淋巴细胞 (iTIL)、错配修复缺陷和 PD-L1 表达缺失显著正相关。Kaplan-Meier 生存分析显示，PBRM1 表达缺失/减弱的 GAC 患者的总生存率显著提高 ( = 0.023)。iTIL 是 GAC 的独立预后因素。PBRM1 表达缺失常与其他 SWI/SNF 复合物亚基基因的突变同时发生，并且存在一些重复的 KEGG 信号变化。PBRM1 基因的异常可能与某些 GAC 的发生有关，并能影响肿瘤免疫活性，从而影响临床病理和预后。它可能是一种潜在有效的免疫治疗预测标志物，也是一种与合成致死相关的新的治疗方法。
