Abstract
BackgroundDNA 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.MethodsQuantitative 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.ResultsHigher 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.ConclusionsOur results suggest an association between TACSTD2 methylation and disease progression and clinical course of RCC.
Highlights
DNA methylation is frequently observed in the development and progression of many human tumors as well as renal cell cancer (RCC)
Our results suggest an association between Tumor Associated Calcium Signal Transducer 2 (TACSTD2) methylation and disease progression and clinical course of RCC
Pathogenesis of different histological subtypes of RCC has been associated with a number of genetic and epigenetic modifications comprehensively analysed in the The Cancer Genome Atlas network (TCGA) study providing molecular data for alterations observed in clear cell RCC (ccRCC) as well as papillary and chromophobe RCC [3]
Summary
DNA methylation is frequently observed in the development and progression of many human tumors as well as renal cell cancer (RCC). Whether TACSTD2 is tumor hypermethylated in RCC or shows association of methylation with adverse clinicopathological parameters and survival of patients has not been investigated at yet. Recent studies demonstrated an association between tumor-specific hypermethylation and overall survival (OS) in patients receiving targeted therapy [16, 17]. Some of these studies included additional functional analyses indicating that statistical association with disease characteristics and functional relevance for marker associated genes might be in concordance; a systematic evaluation of this assumption has not been carried out yet [7, 13]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
