Yang Dinglong, Li Hetong, Chen Yujing, Li Chunjiang, Ren Weiping, Huang Yongbo
Second Clinical Medical College, Shanxi Medical University, Taiyuan, China.
School of Public Health, Xi'an Jiaotong University, Xian, China.
Front Genet. 2022 Jul 15;13:906174. doi: 10.3389/fgene.2022.906174. eCollection 2022.
Previous studies have partly explored the role of B-cell CLL/lymphoma 7 protein family member B () in tumorigenesis and development. However, the prognosis and immunoregulatory value of in pan-cancer patients remains unclear. Through The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases, the distinct expression of gene in 33 tumors and adjacent normal tissues was analyzed. The Kaplan-Meier method (univariate Cox regression analysis and Kaplan-Meier curve) was used to identify the cancer types whose gene expression was related to prognosis. The receiver operating characteristic (ROC) curve was used to elucidate the diagnosis value of gene. Spearman's rank correlation coefficient was used to explore the relationship between gene expression and immune cell infiltration, immune checkpoints, DNA methylation, DNA repair genes, immune-activating genes, immune-suppressing genes, immune subtypes, tumor mutation burden (TMB), and microsatellite instability (MSI). The Wilcoxon rank sum test and Kruskal-Wallis test were used to compare the expression of gene in tumor tissues with different clinicopathological features. Gene set enrichment analysis (GSEA) was conducted to identify the tumor-related pathways in pan-cancer. The Human Protein Atlas (HPA) database was used to verify the gene expression at the protein level. High expression of was associated with an inferior prognosis in glioblastoma multiforme (GBM), glioma (GBMLGG), kidney chromophobe (KICH), brain lower grade glioma (LGG), oral squamous cell carcinoma (OSCC), rectum adenocarcinoma (READ), and uveal melanoma (UVM). Low expression of was associated with a poor prognosis in kidney renal clear cell carcinoma (KIRC), kidney renal papillary cell carcinoma (KIRP), skin cutaneous melanoma (SKCM), thyroid carcinoma (THCA), and sarcoma (SARC). The gene expression had varying degrees of correlation with 24 immune cell subsets in 37 tumor environments such as adrenocortical carcinoma (ACC) and bladder urothelial carcinoma (BCLA). Spearman's rank correlation coefficient showed that gene expression had different degrees of correlation with 47 immune checkpoints, 46 immune-activating genes, 24 immune-suppressing genes, 5 DNA repair genes, and DNA methylation, TMB, and MSI in 39 tumors. GSEA suggested that was notably associated with cancer-related and immune-related pathways. In summary, gene has a high diagnostic and prognostic value in pan-cancer and is related to the infiltration of 24 immune cell subsets in pan-cancer.
以往的研究部分探讨了B细胞慢性淋巴细胞白血病/淋巴瘤7蛋白家族成员B（）在肿瘤发生和发展中的作用。然而，其在泛癌患者中的预后及免疫调节价值仍不清楚。通过癌症基因组图谱（TCGA）和基因型-组织表达（GTEx）数据库，分析了该基因在33种肿瘤及相邻正常组织中的差异表达。采用Kaplan-Meier法（单因素Cox回归分析和Kaplan-Meier曲线）来确定该基因表达与预后相关的癌症类型。采用受试者工作特征（ROC）曲线来阐明该基因的诊断价值。使用Spearman等级相关系数来探索该基因表达与免疫细胞浸润、免疫检查点、DNA甲基化、DNA修复基因、免疫激活基因、免疫抑制基因、免疫亚型、肿瘤突变负荷（TMB）和微卫星不稳定性（MSI）之间的关系。采用Wilcoxon秩和检验和Kruskal-Wallis检验来比较该基因在具有不同临床病理特征的肿瘤组织中的表达。进行基因集富集分析（GSEA）以确定泛癌中与肿瘤相关的通路。利用人类蛋白质图谱（HPA）数据库在蛋白质水平验证该基因的表达。该基因的高表达与多形性胶质母细胞瘤（GBM）、胶质瘤（GBMLGG）、肾嫌色细胞癌（KICH）、低级别脑胶质瘤（LGG）、口腔鳞状细胞癌（OSCC）、直肠腺癌（READ）和葡萄膜黑色素瘤（UVM）的预后较差相关。该基因的低表达与肾透明细胞癌（KIRC）、肾乳头状细胞癌（KIRP）、皮肤黑色素瘤（SKCM）、甲状腺癌（THCA）和肉瘤（SARC）的预后不良相关。在肾上腺皮质癌（ACC）和膀胱尿路上皮癌（BCLA）等37种肿瘤环境中，该基因表达与24种免疫细胞亚群有不同程度的相关性。Spearman等级相关系数表明，在39种肿瘤中，该基因表达与47个免疫检查点、46个免疫激活基因、24个免疫抑制基因、5个DNA修复基因以及DNA甲基化、TMB和MSI有不同程度的相关性。GSEA提示该基因与癌症相关和免疫相关通路显著相关。总之，该基因在泛癌中具有较高的诊断和预后价值，且与泛癌中24种免疫细胞亚群的浸润相关。
