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. 2023 Aug 25;13(1):13898.
doi: 10.1038/s41598-023-41091-8.

A pan-cancer analysis of potassium channel tetramerization domain containing 12 in human cancer

Pan Liu  1 , Zhilan Liu  2 , Qiankun Luo  1 , Qiang Fu  1 , Xu Zhang  1 , Pengfei Yu  1 , Shuai Zhou  3 , Yingying Wang  4 , Jiali Zhang  4 , Song Chen  3   4 , Hongwei Zhang  5 , Qinghai Zhu  6 , Tao Qin  7
Affiliations

A pan-cancer analysis of potassium channel tetramerization domain containing 12 in human cancer

Pan Liu et al. Sci Rep. .

Abstract

Abnormal expression of the potassium channel tetramerization domain containing 12 (KCTD12) is closely related to the occurrence and development of various tumors, but a pan-cancer analysis of KCTD12 has not yet been conducted. We explored the association between KCTD12 and more than 30 human malignancies using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. First, the mRNA and protein levels of KCTD12 were examined and their correlations with tumor stage and survival were explored. Second, we analyzed the infiltration of CD8+ and CD4+ T cells and cancer-associated fibroblasts in tumors and explored the correlation between KCTD12 expression and tumor cell stemness, genomic heterogeneity, and diagnostic specificity. Finally, we explored the molecular mechanisms associated with KCTD12 using KEGG/GO analysis. The results showed that KCTD12 mRNA and protein expression levels decreased in most tumors was significantly associated with the prognosis of tumor patients, and the phosphorylation level of KCTD12 decreased in several tumors, such as S200 and T196, pancreatic adenocarcinoma (PAAD), lung adenocarcinoma (LUAD), and breast invasive cancer (BRCA). The expression of KCTD12 was positively correlated with the degree of cancer-associated fibroblasts infiltration in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), head and neck squamous cell carcinoma (HNSC), PAAD, and stomach adenocarcinoma (STAD). The relationship between KCTD12 expression and CD8+ and CD4+ T cell infiltration was also clarified. KCTD12 showed high diagnostic sensitivity for various types of tumors and may be involved in tumor cell biology by affecting tumor cell stemness, tumor burden, and other characteristics. Finally, we analyzed the molecular functions of KCTD12 and possible KEGG/GO signaling pathways. In this study, we developed a biological marker for diagnosis, prognosis, and immune infiltration of the pan-cancers.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Pan-cancer KCTD12 expression levels. (a,b) Expression levels of KCTD12 mRNA in multiple tumors in TCGA and GTEx databases. (c) The expression levels of KCTD12 protein in various tumors in the CPTAC database.
Figure 2
Figure 2
Effect of KCTD12 on different tumor stages and prognoses. (a) Expression levels of KCTD12 in tumors of different stages. (b,c) The relationship between KCTD12 expression and OS, DFS in tumor patients.
Figure 3
Figure 3
Mutation and phosphorylation analysis in different tumors in the TCGA database. (a) KCTD12 mutation site. (b) Alteration frequency with mutation type of KCTD12. (c) Association of KCTD12 mutation status with OS and DFS in COAD and STES. (d) The expression levels of KCTD12 phosphoprotein in PAAD, LUAD, BRCA, and HNSC based on CPTAC (including S176, S187, S200, and T198 sites).
Figure 4
Figure 4
Infiltration of CAFs in different tumors. (a) Different algorithms based on the cBioPortal showed the infiltration level of CAFs in various tumors. (b) The infiltration level of CAFs in CESC, PAAD, STAD, TGCT, and THYM was positively correlated with KCTD12 expression.
Figure 5
Figure 5
Analysis of KCTD12 and immune cell infiltration. (a) Correlation of the infiltration degree of CD8+ T and CD4+ T cells with KCTD12 according to the cBioPortal. The CD8+ T cell infiltration levels in THYM were negatively correlated with KCTD12 (left panel), and KCTD12 expression was negatively correlated with CD4+ T cells in all tumors (right panel). (b) Correlation analysis of RNA gene modifications (m6A, m5C, and m1A) with KCTD12. (c) Correlation analysis between KCTD12 expression and tumor stemness.
Figure 6
Figure 6
KCTD12 genomic heterogeneity and ROC diagnostic curve. (a) Correlation of KCTD12 with TMB, MSI, NEO, HRD, MATH, and PLOIDYS in multiple malignancies. (b) ROC curve to assess the sensitivity of KCTD12 for tumor diagnosis.
Figure 7
Figure 7
Functional analysis of the KCTD12 gene. (a) Top 50 proteins that interact with KCTD12 as identified by STRING analysis. (b) Among the 100 genes related to KCTD12 in GEPIA 2, the correlation degree of three genes (CSF1R, DCHS1, and MEX3D) with KCTD12 was analyzed. (c) The corresponding heatmap in (b) was generated using TIMER 2.0. (d) KEGG/GO was used to analyze the function of the KCTD12 gene in cells and its possible involvement in signaling pathways [Kanehisa Laboratories (2022). KEGG Database. Retrieved August 9, 2023, from http://www.kegg.jp/kegg/kegg1.html].
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