Epigenetic signature predicts overall survival clear cell renal cell carcinoma

Abstract

Background Recently, increasing study have found that DNA methylation plays an important role in tumor, including clear cell renal cell carcinoma (ccRCC). Methods We used the DNA methylation dataset of The Cancer Genome Atlas (TCGA) database to construct a 31-CpG-based signature which could accurately predict the overall survival of ccRCC. Meanwhile, we constructed a nomogram to predict the prognosis of patients with ccRCC. Result Through LASSO Cox regression analysis, we obtained the 31-CpG-based epigenetic signature which were significantly related to the prognosis of ccRCC. According to the epigenetic signature, patients were divided into two groups with high and low risk, and the predictive value of the epigenetic signature was verified by other two sets. In the training set, hazard ratio (HR) = 13.0, 95% confidence interval (CI) 8.0–21.2, P < 0.0001; testing set: HR = 4.1, CI 2.2–7.7, P < 0.0001; entire set: HR = 7.2, CI 4.9–10.6, P < 0.0001, Moreover, combined with clinical indicators, the prediction of 5-year survival of ccRCC reached an AUC of 0.871. Conclusions Our study constructed a 31-CpG-based epigenetic signature that could accurately predicted overall survival of ccRCC and staging progression of ccRCC. At the same time, we constructed a nomogram, which may facilitate the prediction of prognosis for patients with ccRCC.

Identifying anal and cervical tumorigenesis-associated methylation signaling with machine learning methods

“…For monitoring the status of anal carcinoma, three rules for recognizing three different clusters separately include the functional probes cg01550828 and cg18954144, both of which are associated with anal tumorigenesis as we have discussed above. According to our rules, a higher methylation level of cg01550828 and a lower methylation level of cg18954144 indicate a pathogenic status of anal carcinoma, consistent with previous studies ( 46 , 47 ). Interestingly, we also identified lower methylation of cg01550828, associated with gene RNF168 as a biomarker for pathogenesis of intermediate status (precancerous lesions/intraepithelial neoplasia), providing a novel approach for predicting the precancerous lesion stage.…”

“…The next probe cg25578064 regulates gene SFRS6, which is also a key driver gene for multiple gastrointestinal cancer subtypes ( 45 ), although it has no direct link with anal cancer. No functional genes were annotated around probe cg18954144 but the CpG site has been reported to be a typical signature for cancer overall survival ( 46 ), indicating that such probe may also be valuable for anal carcinoma monitoring. The final biomarker probe cg01550828 regulates a functional gene RNF168, encoding a ring finger protein.…”

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

“…In recent years, several groups have used multi-omic data analysis to reveal groups of differentially methylated and expressed genes in surgically resected specimens of RCC or in the open data of ccRCC in TCGA (TCGA Research Network). The evidence generated confirms cluster analysis based on genomewide promoter methylation serves to identify panels of methylated genes associated to ccRCC disease progression [17,34,[72][73][74][75][76][77][78][79][80][81][82][83]. Some of these panels have been validated in an independent retrospective cohort and some have been incorporated into prognostic risk score models to enhance their prognostic biomarker effect [77,78].…”

An Aging and Senescence-Related Gene Signature for Prognosis Prediction in Clear Cell Renal Cell Carcinoma

“…A number of studies have attempted to develop models to predict the prognosis in ccRCC patients based on gene sequencing and clinical data (Li et al, 2020a;Chen et al, 2020;Hua et al, 2020;Wang et al, 2020;Zhang et al, 2020;Zhong et al, 2020;Xing et al, 2021). However, few results have been applied in clinical practice.…”