DNA methylation of sarcosine dehydrogenase (SARDH) loci as a prognosticator for renal cell carcinoma

Abstract

DNA methylation plays an important role in the genesis and progression of tumor diseases. To identify new DNA methylation markers possibly associated with the clinical characteristics of renal cell carcinoma (RCC), we investigated loci in the sarcosine dehydrogenase (SARDH) gene. SARDH is involved in the metabolism of the glycine-derivative sarcosine and is closely linked through a functional control loop. Statistical evaluation of methylation data and clinical characteristics of patients showed that kidney tumors with clinically aggressive features such as a high tumor stage, positive lymph nodes, distant metastases or a previously advanced tumor status exhibited significantly lower methylation of a locus in the SARDH gene. Moreover, SARDH methylation was found to be a significant prognostic factor for recurrence-free survival in RCC patients showing statistical independence from the clinical prognosticators, grade, stage and state of metastasis. In conclusion, the methylation status of the SARDH-CGI was identified as an independent prognostic candidate marker for RCC.

Sarcosine dehydrogenase as an immune infiltration-associated biomarker for the prognosis of hepatocellular carcinoma

“…Based on these findings, it could be inferred that SARDH is an oncogenic factor in HCC. The low expression of SARDH suggested a worse prognosis in HCC, as well as in other cancers like prostate cancer, colorectal cancer and renal cell carcinoma [17][18][19]. The study also constructed a nomogram that demonstrated SARDH had some predictive power for survival at 1, 3, and 5 years.…”

“…While SARDH methylation has not yet been explored in the context of in HCC, it has been studied in renal cell carcinoma. SARDH hypermethylation was obviously related with the clinical aggressive characteristics and has been recognized as an important factor affecting recurrence-free survival in renal cell carcinoma 18 .…”

“…SARDH is a suppressor gene for incidental colorectal cancer, high expression of which suppresses the biological functions of colorectal cancer cell lines 17 . Notably, SARDH is strongly associated with DNA methylation, serving as a prognostic biomarker for renal cell carcinoma, significantly correlating with clinicopathological features 18 . In prostate cancer, SARDH plays a significant prognostic role by altering the aggressiveness of cancer cells through interaction with TMEFF2 19 .…”

The Role of Epigenetics in the Progression of Clear Cell Renal Cell Carcinoma and the Basis for Future Epigenetic Treatments

“…In this sense, promoter CpG methylation of γ-catenin is considered an independent predictor for survival and disease progression [ 84 ]. Other hypermethylated genes associated with worse RCC disease-specific survival are: GATA Binding Protein 5 ( GATA5 ), that codify for a DNA-binding transcription factor [ 85 , 86 ]; Gremlin 1 ( GREM1 ), related to cytokine activity and bone morphogenic protein [ 87 ]; HIC ZBTB Transcriptional Repressor 1 ( HIC1 ), related both to DNA-binding transcription factor activity and histone deacetylase binding [ 88 ]; Junction Plakoglobin ( JUP ), related to protein homodimerization activity and protein kinase binding [ 84 ]; neural EGFL like 1 ( NELL1 ), linked to calcium ion binding [ 76 ]; Protocadherin 8 ( PCDH8 ), also related to calcium ion binding [ 89 ]; Phosphatase and Tensin Homolog ( PTEN ), related to protein kinase binding [ 90 ]; Ras Association Domain Family Member 1 ( RASSF1A ) that encodes a protein similar to the RAS effector proteins [ 91 , 92 ]; sarcosine dehydrogenase ( SARDH ), associated to oxidoreductase activity [ 93 ]; and Secreted Frizzled Related Protein 1 ( SFRP1 ), related to G protein-coupled receptor activity [ 94 , 95 ]. Very recently some methylated genes with prognostic value in pRCC have also been described [ 96 ].…”

Predictive model for recurrence of renal cell carcinoma by comparing pre‐ and postoperative urinary metabolite concentrations

“…20 Glycine is an essential metabolite for nucleic acid synthesis, and the methylation sarcosine dehydrogenase gene related to a prognostic factor for recurrence-free survival in RCC patients. 21…”