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Clinical and Immunological Significance of ANKRD52 in Pan-Cancer

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Abstract

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.

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Funding

Funding was provided by Haiyan Fund Project of Harbin Medical University Cancer Hospital (Grant nos. JJQN 2019-07, JJMS 2022-06), National Natural Science Foundation of China (Grant no. 82202996), The Fundamental Research Funds for the Provincial Universities (Grant no. 2022-KYYWF-0288), Heilongjiang Postdoctoral Financial Assistance (Grant no. LBH-Z22219), Heilongjiang Provincial Natural Science Foundation Outstanding Youth Project (Grant no. YQ2023H022), China Postdoctoral Science Foundation (Grant no. 2023MD 734172).

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  1. Hui-Zi Yin, and Meng-Chun Zhang are the first authors.

Authors and Affiliations

  1. Department of Breast Radiotherapy, Harbin Medical University Cancer Hospital, 150 Haping Road, Harbin, 150081, China

    Hui-Zi Yin

  2. Key Laboratory of Tumor Biotherapy, Harbin Medical University Cancer Hospital, 150 Haping Road, Harbin, 150081, China

    Hao Wu

  3. Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, 157 Baojian Road, Harbin, 150081, China

    Hui-Zi Yin, Meng-Chun Zhang & Hao Wu

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H-ZY and M-CZ wrote the main manuscript text. H-ZY and HW prepared all figures. All authors reviewed the manuscript.

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Correspondence to Hao Wu.

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Supplementary Information

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10528_2023_10645_MOESM1_ESM.jpg

Supplementary file1 Supplementary Fig. 1: Expression of ANKRD52 in 14 types of tumour tissues and corresponding normal tissues from TCGA database. (JPG 1392 KB)

10528_2023_10645_MOESM2_ESM.jpg

Supplementary file2 Supplementary Fig. 2: Clinical and immunological features of ANKRD52 in BRCA. (A) Relationship of ANKRD52 expression and cancer stage. (B) Genes positively (B1) and negatively (B2) correlated with ANKRD52. (C) The mutation landscapes of top 30 genes with the highest mutation frequency in the ANKRD52 Hexp and Lexp groups. (JPG 4388 KB)

10528_2023_10645_MOESM3_ESM.jpg

Supplementary file3 Supplementary Fig. 3: The relationship of the expression of ANKRD52 and immune- and cancer-associated genes in BRCA. (JPG 4340 KB)

10528_2023_10645_MOESM4_ESM.jpg

Supplementary file4 Supplementary Fig. 4: Construction and validation of a nomogram for ANKRD52 in the train and test sets. (A) Test set of calibration curves for predicting 3- and 5-year OS in BRCA. (B) Test set of ROC curve for predicting 3-year OS in BRCA. (C) Test set of ROC curve for predicting 5-year OS in BRCA. (D) Train set of calibration curves for predicting 3- and 5-year OS in BRCA. (E) Train set of ROC curve for predicting 3-year OS in BRCA. (F) Train set of ROC curve for predicting 5-year OS in BRCA. (JPG 2820 KB)

10528_2023_10645_MOESM5_ESM.jpg

Supplementary file5 Supplementary Fig. 5: Mutation landscapes of top 30 genes with the highest mutation frequency between patients with high- and low-expression of ANKRD52. (A) ACC (B) BLCA (C) CESE (D) CHOL (E) COAD (F) DLBC (G) ESCA (H) GBM (I) HNSC (J) KICH (K) KIRC (L) KIRP (M) LAML (N) LGG (O) LIHC (P) LUAD (Q) LUSC (R) MESO (S) OV (T) PAAD (U) PCPG (V) PRAD (W) READ (X) SARC (Y) SKCM (Z) STAD (AA) TGCT (BB) THCA (CC) THYM (DD) UCEC (EE) UCS (FF) UVM. (JPG 8522 KB)

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Yin, HZ., Zhang, MC. & Wu, H. Clinical and Immunological Significance of ANKRD52 in Pan-Cancer. Biochem Genet (2024). https://doi.org/10.1007/s10528-023-10645-w

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