全癌种分析与单细胞分析揭示FAM110B作为生存和免疫治疗潜在靶点

Pan-cancer analysis and single-cell analysis reveals FAM110B as a potential target for survival and immunotherapy

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Frontiers in Molecular Biosciences

影响因子:4

分区:生物学3区 / 生化与分子生物学3区

发表日期:2024

作者: Yuwei Li, Xiaoxi Li, Bihua Wu, Shuangyan Su, Yunpeng Su, Le Guo

DOI: 10.3389/fmolb.2024.1424104

摘要

背景：FAM110B属于具有110序列相似性的家族（FAM110），位于中心体和有丝分裂纺锤体中。早期研究已将FAM110B与肿瘤细胞的生长相关联。关于FAM110B在肿瘤微环境中的功能及其在全癌种中的作用尚不清楚。方法：我们结合TCGA和GTEx数据库，评估FAM110B在正常组织和全癌种组织中的表达变化。利用cBioPortal和GSCALite平台分析FAM110B的基因组变化和甲基化变异。采用Cox回归、Kaplan-Meier及SangerBox分析FAM110B在临床特征及预后中的作用。相关性研究旨在探讨FAM110B与免疫相关基因、肿瘤突变负荷（TMB）、微卫星不稳定性（MSI）、免疫相关基因和免疫检查点之间的关系。利用ESTIMATE、EPIC、QUANTISEQ和MCPCOUNTER方法计算FAM110B表达与肿瘤免疫微环境的交互作用。通过TISCH和CancerSEA单细胞数据库分析FAM110B的免疫渗透和功能。最后，利用GDSC和CTRP数据库评估FAM110B对小分子药物的敏感性。结果：FAM110B的转录和蛋白表达在不同癌种中差异显著，对某些肿瘤的预后具有预测价值；包括脑低级别胶质瘤（LGG）、胃腺癌（STAD）、胰腺腺癌（PAAD）等。在肿瘤微环境中，FAM110B的表达水平与免疫细胞浸润、免疫检查点免疫调节基因、肿瘤突变负荷及微卫星脆弱性存在一定相关性。结论：本研究探讨了FAM110B作为全癌种免疫治疗反应预测标志物的潜力，为癌症治疗提供理论基础。

Abstract

Background: FAM110B belongs to the family that has a 110 sequence similarity (FAM110) and is located in the centrosome and mitotic spindle. FAM110B has been linked to tumor cell growth in earlier research. Uncertainty exists regarding FAM110B's function within the tumor microenvironment is unclear as well as pan-cancer. Methods: In order to assess the variation in FAM110B expression within normal and pan-cancer tissues, we combined the TCGA and GTEx databases. The cBioPortal database and the GSCALite platform were used to examine the variation in genome and methylation alteration of FAM110B. Cox regression, Kaplan-Meier, and SangerBox were employed to examine the clinical features and prognosis of FAM110B and pan-cancer. The purpose of the correlational research was to investigate the associations within immunerelated genes, tumor mutation burden, microsatellite instability, immune-related genes, and immunological checkpoints and FAM110B expression. ESTIMATE, EPIC, QUANTISEQ, and MCPCOUNTER methods were used to calculate the interaction among FAM110B expression as well as the tumor immune microenvironment. The immunoinfiltration and function of FAM110B were analyzed by single-cell databases (TISCH and CancerSEA). Finally, we evaluated the sensitivity of FAM110B to small-molecule medications through GDSC and CTRP databases. Results: The transcription and protein expression of FAM110B varies significantly throughout cancer types, and this has predictive value for the prognosis of some tumors; including brain lower grade glioma (LGG), stomach adenocarcinoma (STAD), pancreatic adenocarcinoma (PAAD), etc. In the tumor microenvironment, the expression level of FAM110B was associated with immune cell infiltration, immune checkpoint immune regulatory genes, tumor mutational burden, and microsatellite fragility to a certain extent. Conclusion: This work investigates the possibility of utility of FAM110B as a marker to forecast pan-cancer immunotherapy response, providing a theoretical basis for cancer therapy.