DNA methylation status predicts survival in metastasis free clear cell renal cell carcinoma
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PROVIDER: PRJNA453379 | ENA |
REPOSITORIES: ENA
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Project description:Background: Clear cell renal cell carcinomas (ccRCCs) display divergent clinical phenotypes. Up to one third of patients with local disease at diagnosis will progress. Therefore, it is a need to identify patients at risk for recurrence. In the present study, we analyzed genome-wide promoter DNA methylation at diagnosis in relation to clinicopathological parameters, in order to identify DNA methylation profiles associated with risk for progress. Method: DNA methylation status in 155,931 CpGs located in gene promoter regions was analyzed by Illumina HumanMethylation450K arrays in diagnostic tissue samples from 115 ccRCC patients. Methylation profiles were compared with genetic aberrations and clinicopathological parameters. Results: The tumors separated into two clusters based on genome-wide promoter methylation status. The tumors in these clusters differed in tumor diameter (p < 0.001), TNM stage (p < 0.001), morphological grade (p < 0.001), and patients outcome (5 year cancer specific survival (pCSS5yr) 72 % in cluster A vs 26 % in cluster B, p < 0.001). When metastasis-status (M0/M1) and cluster A/B status at diagnosis were combined, we found poor survival in M1 patients regardless of cluster A/B status (pCSS5yr 9 % vs 6 %). In M0 patients, the cluster status clearly separated in survival (pCSS5yr 81 % vs 17 %; p < 0.001). We identified a methylation profile of 398 CpGs that was associated with progress of disease, which included differently methylated CpG sites in the SMAD6, SOCS3 and MX2 genes. An integrated genomic and epigenomic analysis revealed significant correlations between the total number of genetic aberrations and hypermethylated CpGs (R = 0.435, p > 0.001), and predicted mitotic age (R = 0.407, p < 0.001). Conclusion: DNA methylation analysis at diagnosis in ccRCC has the potential to improve outcome-prediction and therapy stratification.
2019-01-23 | GSE113501 | GEO
Project description:A transcriptional metastatic signature predicts survival in clear cell renal cell carcinoma
| PRJNA739195 | ENA
Project description:Detailed genetic profiling of clear cell Renal Cell Carcinoma (ccRCC) has shown that these tumors are characterized by large genetic heterogeneity with some genomic regions commonly affected by structural changes. Loss on chromosomes 3p and 14q, and gain on 5q and 7 are examples of alterations commonly reported in ccRCC. However, there is no consensus regarding the potential prognostic information carried by the identified alterations. We report on poorer outcome for patients with gain on 5q and 7, and loss on 9p, 9q and 14q. These aberrations were in addition found more frequently in metastasized tumors, suggesting that they are markers for advanced disease. Furthermore, the presence of M-bM-^IM-% 4 common aberrations was associated with decreased survival time. Shorter relative telomere length (RTL) has been associated with loss of chromosomal regions in ccRCC tumors, but we found no significant associations between tumor RTL and chromosomal deletions. However, significantly lower tumor-to-nontumor (T/N) RTL ratio was detected for patients with loss on 4q and 9p. Finally, we found a minimum region (MR) of genetic loss of 1.4 Mbp on chromosome 9p and this region contains only one gene, the tumor suppressor candidate 1 gene (TUSC1). TUSC1 has been implicated in lung carcinogenesis and our result further strengthens its role in tumorigenesis. Seventy-four ccRCC tumors and 22 paired normal kidney cortex and blood samples were genotyped on Illuminas HumanCytoSNP-12 bead chips.
2014-07-01 | E-GEOD-30460 | biostudies-arrayexpress
Project description:BackgroundRecently, increasing study have found that DNA methylation plays an important role in tumor, including clear cell renal cell carcinoma (ccRCC).MethodsWe 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.ResultThrough 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.ConclusionsOur 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.
| S-EPMC7686748 | biostudies-literature
Project description:Detailed genetic profiling of clear cell Renal Cell Carcinoma (ccRCC) has shown that these tumors are characterized by large genetic heterogeneity with some genomic regions commonly affected by structural changes. Loss on chromosomes 3p and 14q, and gain on 5q and 7 are examples of alterations commonly reported in ccRCC. However, there is no consensus regarding the potential prognostic information carried by the identified alterations. We report on poorer outcome for patients with gain on 5q and 7, and loss on 9p, 9q and 14q. These aberrations were in addition found more frequently in metastasized tumors, suggesting that they are markers for advanced disease. Furthermore, the presence of ≥ 4 common aberrations was associated with decreased survival time. Shorter relative telomere length (RTL) has been associated with loss of chromosomal regions in ccRCC tumors, but we found no significant associations between tumor RTL and chromosomal deletions. However, significantly lower tumor-to-nontumor (T/N) RTL ratio was detected for patients with loss on 4q and 9p. Finally, we found a minimum region (MR) of genetic loss of 1.4 Mbp on chromosome 9p and this region contains only one gene, the tumor suppressor candidate 1 gene (TUSC1). TUSC1 has been implicated in lung carcinogenesis and our result further strengthens its role in tumorigenesis.
2014-07-01 | GSE30460 | GEO
Project description:Novel single cell technologies have paved the way for the characterization and improved biological understanding of clear cell renal cell carcinoma (ccRCC) where the focus has been mostly on the immunological compartments of the tumor microenvironment (TME). However, the identification of metastatic tumor cell clones, and the stromal compartments of TME of untreated ccRCC patients still remains to be elucidated. Here we perform single-cell RNA-sequencing on treatment naive ccRCC and adjacent normal kidney tissue.
2022-08-18 | GSE178481 | GEO
Project description:Clear-cell renal-cell carcinoma (ccRCC) is the most common pathological subtype of renal cell carcinoma (RCC), accounting for about 80% of RCC. In order to find potential prognostic biomarkers in ccRCC, we presented a four-gene signature to evaluate the prognosis of ccRCC. SurvExpress and immunohistochemical (IHC) staining of tissue microarrays were used to analyze the association between the four genes and the prognosis of ccRCC. Data from TCGA dataset revealed a prognostic prompt function of the four genes (PTEN, PIK3C2A, ITPA and BCL3). Further discovery suggested that the four-gene signature predicted survival better than any of the four genes alone. Moreover, IHC staining demonstrated a consistent result with TCGA, indicating that the signature was an independent prognostic factor of survival in ccRCC. Univariate and multivariate Cox proportional hazard regression analysis were conducted to verify the association of clinicopathological variables and the four genes' expression levels with survival. The results further testified that the risk (four-gene signature) was an independent prognostic factors of both Overall Survival (OS) and Disease-free Survival (DFS) (P<0.05). In conclusion, the four-gene signature was correlated with the survival of ccRCC, and therefore, may help to provide significant clinical implications for predicting the prognosis of patients.
| S-EPMC5347726 | biostudies-literature
Project description:Clear-cell renal cell carcinoma (ccRCC) is the major renal cell carcinoma subtype, but its postsurgical prognosis varies among individual patients.We used gene expression, machine learning (random forest variable hunting), and Cox regression analysis to develop a risk score model based on 15 genes to predict survival of patients with ccRCC in the The Cancer Genome Atlas dataset (N?=?533). We validated this model in another cohort, and analyzed correlations between risk score and other clinical indicators.Patients in the high-risk group had significantly worse overall survival (OS) than did those in the low-risk group (P?=?5.6e-16); recurrence-free survival showed a similar pattern. This result was reproducible in another dataset, E-MTAB-1980 (N?=?101, P?=?.00029). We evaluated correlations between risk score and other clinical indicators. Risk was independent of age and sex, but was significantly associated with hemoglobin level, primary tumor size, and grade. Radiation therapy also had no effect on the prognostic value of the risk score. Cox multivariate regression showed risk score to be an important indicator for ccRCC prognosis. We plotted a nomogram for 3-year OS to facilitate use of risk score and other indicators.The risk score model based on expression of the 15 selected genes can predict survival of patients with ccRCC.
| S-EPMC6113007 | biostudies-other
Project description:In this retrospective analysis, we evaluated associations between albumin to globulin ratio (AGR), clinicopathological characteristics, and survival in 592 patients with localized or locally advanced clear cell renal cell carcinoma (CCRCC) prior to nephrectomy. We found that low AGR was associated with more aggressive tumor behavior; patients with low AGR had poorer overall survival (OS) and cancer-specific survival (CSS) in Kaplan-Meier survival analyses both before and after propensity score matching, which was used to compensate for differences in baseline clinicopathological characteristics. AGR was an independent prognostic factor for both OS (HR: 6.799; 95% CI: 3.215-14.377; P < 0.001) and CSS (HR: 8.806; 95% CI: 3.891-19.928; P < 0.001), and its prognostic value was higher than that of other established inflammation-based prognostic scores. When AGR was incorporated into a prognostic model that included T stage, neutrophil to lymphocyte ratio (NLR), and monocyte to lymphocyte ratio (MLR), the resulting nomogram predicted 3- and 5-year OS in the patients more accurately than when AGR was not included. In conclusion, AGR may be particularly useful for improving clinical outcome predictions for patients with localized or locally advanced CCRCC.
| S-EPMC5564647 | biostudies-other
Project description:Wider clinical applications of 9p status in clear cell renal cell carcinoma (ccRCC) are limited owing to the lack of validation and consensus for interphase fluorescent in situ hybridisation (I-FISH) scoring technique. The aim of this study was to analytically validate the applicability of I-FISH in assessing 9p deletion in ccRCC and to clinically assess its long-term prognostic impact following surgical excision of ccRCC.Tissue microarrays were constructed from 108 renal cell carcinoma (RCC) tumour paraffin blocks. Interphase fluorescent in situ hybridisation analysis was undertaken based on preset criteria by two independent observers to assess interobserver variability. 9p status in ccRCC tumours was determined and correlated to clinicopathological variables, recurrence-free survival and disease-specific survival.There were 80 ccRCCs with valid 9p scoring and a median follow-up of 95 months. Kappa statistic for interobserver variability was 0.71 (good agreement). 9p deletion was detected in 44% of ccRCCs. 9p loss was associated with higher stage, larger tumours, necrosis, microvascular and renal vein invasion, and higher SSIGN (stage, size, grade and necrosis) score. Patients with 9p-deleted ccRCC were at a higher risk of recurrence (P=0.008) and RCC-specific mortality (P=0.001). On multivariate analysis, 9p deletion was an independent predictor of recurrence (hazard ratio 4.323; P=0.021) and RCC-specific mortality (hazard ratio 4.603; P=0.007). The predictive accuracy of SSIGN score improved from 87.7% to 93.1% by integrating 9p status to the model (P=0.001).Loss of 9p is associated with aggressive ccRCC and worse prognosis in patients following surgery. Our findings independently confirm the findings of previous reports relying on I-FISH to detect 9p (CDKN2A) deletion.
| S-EPMC4183850 | biostudies-other