BRK1作为潜在的免疫治疗靶点的全癌分析。
Pan-cancer analysis of BRK1 as a potential immunotherapeutic target.
发表日期:2023 Mar 29
作者:
Xuefeng Wang, Yanru Tang, Rui Liu, Wentao Li, Shiyue Liu, Xinhong Zhou
来源:
GENES & DEVELOPMENT
摘要:
越来越多的证据支持几种癌症的进展与BRK1之间的关联。然而,BRK1基因在癌症中的异常表达的临床意义还不清楚。本研究旨在研究BRK1作为潜在免疫治疗靶点的可能性和影响,为肝癌免疫治疗提供更好的选择。我们探讨了BRK1在不同癌症中的表达预测作用,包括差异表达、肿瘤微环境、微卫星不稳定性、肿瘤突变负荷、免疫检查点分子、免疫相关和细胞周期相关信号通路,以及药物反应敏感性等不同生物信息学方面。最后,我们通过免疫组织化学验证了BRK1在肝细胞癌中的表达情况。BRK1在多种癌症中高表达,与广泛的主要癌症类型的预后和疾病进展呈负相关。此外,BRK1的表达与肿瘤的微卫星不稳定性和突变负荷有关。肿瘤的免疫评分、免疫浸润、免疫检查点分子和基质评分与BRK1的表达也存在显著相关性。在肝细胞癌中,BRK1与多个信号通路和免疫细胞浸润相关,可能影响多个关键的免疫相关调控基因,使其成为一个优秀的生物标志物,可能是免疫药物的敏感靶点。我们的研究表明,BRK1可能是潜在的预后标记和免疫治疗靶点,并可能与不同恶性肿瘤,包括肝细胞癌的恶性预后相关联。
Increasing evidence supports the connection between the progression of several cancers and BRK1. However, the clinical significance of aberrant BRK1 gene expression in cancer is unknown. This study is conducted to investigate the possibility and effect of BRK1 as a potential immunotherapy target, to deliver a better option for liver cancer immunotherapy. We explored the predictive role of BRK1 expression in a variety of cancers from different bioinformatics, including differential expression in different cancers, tumor microenvironment (TME), microsatellite instability (MSI), tumor mutational burden (TMB), immune checkpoint molecules, immune-related and cell cycle-related signalling pathways, and drug response sensitivity. Finally, we verified the expression of BRK1 in hepatocellular carcinoma using immunohistochemistry. BRK1 is overexpressed in multiple cancers and displays a negative association with prognosis and progression of disease in a wide range of main cancer types. Additionally, the expression of BRK1 is related to MSI and TMB of tumors. There was also a remarkable correlation between the expression of BRK1 and immune score, immune infiltration, immune checkpoint molecules and a stromal score of tumors. In hepatocellular carcinoma, BRK1 is associated with several signaling pathways and immune cell infiltration may affect several key immune-related regulatory genes, making it an excellent biomarker and may be a sensitive target for immune drugs.Our research suggests that BRK1 may be a potential prognostic marker and target for immunotherapy and may be associated with poor prognosis in diverse malignancies, including hepatocellular carcinoma.