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Background  DNA methylation is frequently observed in the development and progression of many human tumors as well as renal cell cancer (RCC). Tumor Associated Calcium Signal Transducer 2 (TACSTD2) participates in cell cycle progression through MAPK signalling pathway activation. Moreover, tumor-specific hypermethylation and association with aggressive cancer characteristics has been found for lung adenocarcinoma, hepatocellular carcinoma and cholangiocarcinoma. Whether  TACSTD2  is tumor specifically hypermethylated in RCC or shows association of methylation with adverse clinicopathological parameters and survival of patients has not been investigated at yet.    Methods  Quantitative methylation-specific PCR (qMSP) analysis of a locus in the intron 1 region of  TACSTD2  gene was carried out in a cross-sectional study of 127 paired RCC and normal samples. In silico analysis of  TACSTD2  methylation in the TCGA Kidney Renal Clear Cell Carcinoma (KIRC) dataset of 280 patients served as validation cohort. Statistical analyses were carried out using the two-sided paired t-test for matched tumor and normal sample comparisons, logistic regression for subgroup comparisons, Cox regression for analysis of recurrence free survival (RFS) and Pearson correlation analysis for correlation of  TACSTD2  methylation and  TACSTD2  mRNA in KIRC data.    Results  Higher methylation levels in RCC were significantly associated with advanced disease ( p  < 0.001), high tumor stage ( p  = 0.003), tumor differentiation ( p  = 0.033) and presence of lymph node ( p  = 0.021) or distant metastases ( p  = 0.008).  TACSTD2  hypermethylation was associated with a shorter RFS of patients and demonstrate statistical independency from clinical parameters as state of metastasis, tumor stage, grade and state of advanced disease. In silico validation using TCGA KIRC data also demonstrated association of  TACSTD2  loci with adverse clinicopathology and shortened RFS of patients. In addition, in silico analyses of TCGA KIRC data showed an inverse correlation between DNA methylation levels of TACSTD2 and mRNA expression.    Conclusions  Our results suggest an association between  TACSTD2  methylation and disease progression and clinical course of RCC.    Supplementary Information  The online version contains supplementary material available at 10.1186/s12885-021-08172-1.

DNA methylation of tumor associated calcium signal transducer 2 (TACSTD2) loci shows association with clinically aggressive renal cell cancers