Department of Breast Radiotherapy, Harbin Medical University Cancer Hospital, 150 Haping Road, Harbin, 150081, China.
Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, 157 Baojian Road, Harbin, 150081, China.
Biochem Genet. 2024 Dec;62(6):4335-4358. doi: 10.1007/s10528-023-10645-w. Epub 2024 Jan 31.
Ankyrin repeat domain 52 (ANKRD52) is a regulatory component of the protein phosphatase 6 (PP6) holoenzyme. Evidence has emerged to suggest involvement of ANKRD52 in tumor metastases and cancer cell escape from T cell-mediated elimination and immunotherapy but there has been no research across different cancer types. The current study explored the biological functions of ANKRD52 by combining data from many databases. The aim was to expose new diagnostic or treatment biomarkers for malignant tumors. The roles of ANKRD52 with respect to immunotherapy in 33 human cancer types were analyzed by combining data from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), Cancer Cell Line Encyclopedia (CCLE), UCSC Xena, the Tumor Immune Estimation Resource (TIMER), TISIDB and Cellminer. Bioinformatics methods were used to analyze the association between ANKRD52 expression and prognosis, immunological indicators (immune cell infiltration, ESTIMATE scores and tumor microenvironment (TME) signatures), tumor mutational burden (TMB), microsatellite instability (MSI) and drug sensitivity. ANKRD52 expression was generally higher in 24 tumor tissues than in normal tissues and was associated with poor prognosis, especially in kidney chromophobe (KICH). Lower expression was observed in advanced cancer. ANKRD52 expression was strongly linked to major immunological indicators, such as immune cell infiltration, ESTIMATE scores, TME signatures, as well as expression of immune and tumor-related genes. Expression was also associated with indicators of immunotherapy efficacy and outcome, such as TMB in 7 cancer types and MSI in 12. In addition, ANKRD52 expression was linked to sensitivity to a number of anticancer drugs. ANKRD52 had a distinct immune function in breast invasive carcinoma (BRCA) that correlated negatively with most immune indicators. Expression was enriched in proliferation-, differentiation- and metabolism-related pathways and linked to other immune cells and TME signatures. A nomogram to predict 3- or 5-year overall survival (OS) of patients with BRCA was constructed. ANKRD52 may have utility as an oncological and immunological biomarker. New insights into oncogenesis are presented and the development of ANKRD52-targeting to increase the therapeutic efficacy of immunotherapy combined with chemotherapy explored.
锚蛋白重复域 52（ANKRD52）是蛋白磷酸酶 6（PP6）全酶的调节成分。有证据表明 ANKRD52 参与肿瘤转移和癌细胞逃避 T 细胞介导的消除和免疫治疗，但不同癌症类型之间的研究尚未开展。本研究通过结合多个数据库中的数据来探索 ANKRD52 的生物学功能，旨在为恶性肿瘤暴露新的诊断或治疗生物标志物。通过结合癌症基因组图谱（TCGA）、基因-组织表达（GTEx）、癌症细胞系百科全书（CCLE）、UCSC Xena、肿瘤免疫估计资源（TIMER）、TISIDB 和 Cellminer 中的数据，分析了 ANKRD52 在 33 种人类癌症类型中的免疫治疗作用。生物信息学方法用于分析 ANKRD52 表达与预后、免疫指标（免疫细胞浸润、ESTIMATE 评分和肿瘤微环境（TME）特征）、肿瘤突变负荷（TMB）、微卫星不稳定性（MSI）和药物敏感性之间的关联。ANKRD52 表达在 24 种肿瘤组织中普遍高于正常组织，与预后不良相关，尤其是在肾嫌色细胞癌（KICH）中。在晚期癌症中观察到较低的表达。ANKRD52 表达与主要免疫指标密切相关，如免疫细胞浸润、ESTIMATE 评分、TME 特征以及免疫和肿瘤相关基因的表达。它还与免疫治疗疗效和结果的指标相关，如 7 种癌症类型中的 TMB 和 12 种癌症类型中的 MSI。此外，ANKRD52 表达与多种抗癌药物的敏感性相关。ANKRD52 在乳腺癌浸润性癌（BRCA）中具有独特的免疫功能，与大多数免疫指标呈负相关。表达在增殖、分化和代谢相关途径中富集，并与其他免疫细胞和 TME 特征相关。构建了一个预测 BRCA 患者 3 年或 5 年总生存率（OS）的列线图。ANKRD52 可能作为一种肿瘤学和免疫学生物标志物具有实用价值。本研究提出了新的肿瘤发生见解，并探索了针对 ANKRD52 的靶向治疗以提高免疫治疗联合化疗的疗效。
