Zhou Zhixian, Yin Huan, Suye Suye, He Jiarong, Fu Chun
Department of Obstetrics and Gynecology, Second Xiangya Hospital, Central South University, Changsha, China.
Department of Neurosurgery, Second Xiangya Hospital, Central South University, Changsha, China.
Front Genet. 2023 Jan 4;13:1024989. doi: 10.3389/fgene.2022.1024989. eCollection 2022.
Fanconi anemia (FA) genes contribute to tumorigenesis by regulating DNA repair. Despite its importance for assembly and functionality of the FA core complex, no pan-cancer analysis of was performed. We aimed to provide a comprehensive understanding of the role of in cancers. Based on The Cancer Genome Atlas (TCGA), Cancer Cell Line Encyclopedia (CCLE), Genotype Tissue-Expression (GTEx), Human Protein Atlas (HPA), Gene Expression Omnibus (GEO), and Cancer Single-cell Atlas (CancerSEA) databases, we investigated the carcinogenicity of using various bioinformatics methods, including expression and prognosis, immune invasion, tumor mutation burden, microsatellite instability, and neoantigens. We monitored mutations in mice that caused tumorigenesis. expression and activity scores were upregulated in 15 and 21 cancers. High expression of affected shorter overall survival (OS) in seven cancers and longer overall survival in three cancers. It was correlated with shorter overall survival and progression-free interval (PFI) in endometrial cancer and longer overall survival and PFI in cervical cancer. expression negatively correlated with stromal/immune scores in 21 cancers including cervical cancer, endometrial cancer, and ovarian cancer. expression negatively correlated with CD8 T cells in endometrial cancer and positively correlated with M1 macrophages in cervical cancer, possibly related to cancer prognosis. positively correlated with immune checkpoint inhibitors PD-1, PD-L1, and CTLA4 in endometrial cancer and ovarian cancer. expression positively correlated with microsatellite instability, tumor mutational burden, and neoantigens in 7, 22, and five cancers, especially in endometrial cancer, potentially increasing the effectiveness of immunotherapy. Single-cell sequencing data showed was primarily expressed in cancer cells in cervical and ovarian cancer, and in fibroblasts in endometrial cancer. heterozygous mutant mice had increased tumor incidences and shorter overall survival and tumor-free survival (TFS) than homozygous mutant mice and wild-type mice. Conclusively, potential to serve as a biomarker for cancer prognosis and may predict cancer immunotherapy responses. heterozygous mutant resulted in increased tumorigenesis and poor prognosis in mice.
范可尼贫血（FA）基因通过调节DNA修复促进肿瘤发生。尽管其对FA核心复合物的组装和功能很重要，但尚未对其进行泛癌分析。我们旨在全面了解其在癌症中的作用。基于癌症基因组图谱（TCGA）、癌细胞系百科全书（CCLE）、基因型组织表达（GTEx）、人类蛋白质图谱（HPA）、基因表达综合数据库（GEO）和癌症单细胞图谱（CancerSEA）数据库，我们使用多种生物信息学方法研究了其致癌性，包括其表达和预后、免疫浸润、肿瘤突变负担、微卫星不稳定性和新抗原。我们监测了导致肿瘤发生的小鼠中的突变。在15种和21种癌症中表达和活性评分上调。其高表达在7种癌症中影响较短的总生存期（OS），在3种癌症中影响较长的总生存期。它与子宫内膜癌较短的总生存期和无进展生存期（PFI）相关，与宫颈癌较长的总生存期和PFI相关。在包括宫颈癌、子宫内膜癌和卵巢癌在内的21种癌症中，其表达与基质/免疫评分呈负相关。在子宫内膜癌中，其表达与CD8 T细胞呈负相关，在宫颈癌中与M1巨噬细胞呈正相关，这可能与癌症预后有关。在子宫内膜癌和卵巢癌中，其与免疫检查点抑制剂PD-1、PD-L1和CTLA4呈正相关。在7种、22种和5种癌症中，尤其是在子宫内膜癌中，其表达与微卫星不稳定性、肿瘤突变负担和新抗原呈正相关，这可能会提高免疫治疗的有效性。单细胞测序数据显示，在宫颈癌和卵巢癌中主要在癌细胞中表达，在子宫内膜癌中在成纤维细胞中表达。杂合突变小鼠比纯合突变小鼠和野生型小鼠具有更高的肿瘤发生率、更短的总生存期和无瘤生存期（TFS）。总之，有潜力作为癌症预后的生物标志物，并可能预测癌症免疫治疗反应。杂合突变导致小鼠肿瘤发生增加和预后不良。
