Liu Renwang, Zhu Guangsheng, Li Mingbiao, Cao Peijun, Li Xuanguang, Zhang Xiuwen, Huang Hua, Song Zuoqing, Chen Jun
Department of Lung Cancer Surgery, Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin, China.
Tianjin Key Laboratory of Lung Cancer Metastasis and Tumour Microenvironment, Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin, China.
Front Genet. 2022 Nov 16;13:971033. doi: 10.3389/fgene.2022.971033. eCollection 2022.
Although RAD51 associated protein 1 (RAD51AP1) is crucial in genome stability maintenance, it also promotes cancer development with an unclear mechanism. In this study, we collected intact expression data of RAD51AP1 from the public database, and verified it was significantly over-expressed in 33 cancer types and correlated with poor prognosis in 13 cancer types, including glioma, adrenocortical carcinoma, lung adenocarcinoma. We further authenticated that RAD51AP1 is up-regulated in several typical cancer cell lines and promotes cancer cell proliferation . Moreover, we also demonstrated that RAD51AP1 was significantly positively related to cancer stemness score mRNAsi in 27 cancer types and broadly correlated to tumor-infiltrating immune cells in various cancers in a diverse manner. It was also negatively associated with immunophenoscore (IPS) and Estimation of STromal and Immune cells in MAlignant Tumours using Expression data (ESTIMATE) scores and positively correlated with mutant-allele tumor heterogeneity (MATH), tumor mutational burden (TMB), microsatellite instability (MSI), and PD-L1 expression in multiple cancers. The tumor stemness enhancing and tumor immune microenvironment affecting functions of RAD51AP1 might compose its carcinogenesis mechanism. Further investigations beyond the bioinformatics level should confirm these findings in each specific cancer.
尽管RAD51相关蛋白1(RAD51AP1)在维持基因组稳定性方面至关重要,但它也以不明机制促进癌症发展。在本研究中,我们从公共数据库收集了RAD51AP1的完整表达数据,并证实其在33种癌症类型中显著过表达,且与13种癌症类型(包括胶质瘤、肾上腺皮质癌、肺腺癌)的不良预后相关。我们进一步验证了RAD51AP1在几种典型癌细胞系中上调并促进癌细胞增殖。此外,我们还证明RAD51AP1在27种癌症类型中与癌症干性评分mRNAsi显著正相关,并以多种方式与各种癌症中的肿瘤浸润免疫细胞广泛相关。它还与免疫表型评分(IPS)以及使用表达数据估计恶性肿瘤中的基质和免疫细胞(ESTIMATE)评分呈负相关,与多种癌症中的突变等位基因肿瘤异质性(MATH)、肿瘤突变负担(TMB)、微卫星不稳定性(MSI)和PD-L1表达呈正相关。RAD51AP1增强肿瘤干性和影响肿瘤免疫微环境的功能可能构成其致癌机制。生物信息学水平之外的进一步研究应在每种特定癌症中证实这些发现。