KCTD12 is a prognostic marker of breast cancer and correlates with tumor immune cell infiltration

Zhi Wang; Di Wu; Menglu Dong; Yu Xia; Tao Xu

doi:10.21037/tcr-20-2099

KCTD12 is a prognostic marker of breast cancer and correlates with tumor immune cell infiltration

Transl Cancer Res. 2021 Jan;10(1):261-272. doi: 10.21037/tcr-20-2099.

Authors

Zhi Wang¹, Di Wu¹, Menglu Dong², Yu Xia¹, Tao Xu^{1

2}

Affiliations

¹ Department of Obstetrics and Gynecology, Cancer Biology Research Center, Tongji Hospital, Tongji Medical College of HUST, Wuhan, China.
² Department of Thyroid and Breast Surgery, Tongji Hospital, Tongji Medical College of HUST, Wuhan, China.

Abstract

Background: Annually, breast cancer (BC) is the most common newly diagnosed cancer in females. The relatively crude measures of the molecular phenotypes of BC have not provided a comprehensive understanding of its molecular architecture. To a certain extent, this has resulted in many patients being over- or undertreated. Therefore, novel biomarkers that help to improve patients' outcomes are required. The potassium channel tetramerization domain containing 12 (KCTD12) is one such candidate.

Methods: Ribonucleic acid-sequencing (RNA-Seq) filings along with corresponding clinical information of BC samples were obtained from The Cancer Genome Atlas (TCGA) program databases to evaluate the associations between KCTD12 expression levels and clinical features. The prognostic value of KCTD12 in patients was examined by Kaplan-Meier survival analysis and PrognoScan database analysis. To identify the main functions of KCTD12 in BC, we performed gene set enrichment analysis (GSEA) in BC samples and cell lines. The correlations between KCTD12 expression and tumor-infiltrating lymphocyte quantities was confirmed using two online tools: Tumor Immune Estimation Resource and the Gene Expression Profiling Interaction Analysis 2.

Results: KCTD12 expression was significantly decreased in cancer samples compared to normal samples, and was lowly expressed in aggressive disease relative to initial disease. Patients with lower KCTD12 expression levels showed a shorter overall survival and a shorter recurrence-free survival, indicating a worse prognosis. We found that genes of BC in the high-KCTD12 expression group were enriched in immune response pathways. Finally, the positive correlations between the expression of tumor-infiltrating lymphocytes, programmed cell-death ligand 1 (PD-L1), and programmed cell-death protein 1 (PD-1), and KCTD12 expression were confirmed.

Conclusions: KCTD12 can be considered a biomarker to predict the prognosis of BC patients. KCTD12 may also help to predict patient response to PD-L1 or PD-1 inhibitor treatment.

Keywords: Potassium channel tetramerization domain containing 12 (KCTD12); breast cancer (BC); immune infiltration; prognosis; programmed cell-death ligand 1 (PD-L1); programmed cell-death protein 1 (PD-1).