scholarly journals Identification of a Novel Epigenetic Signature CHFR as a Potential Prognostic Gene Involved in Metastatic Clear Cell Renal Cell Carcinoma

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiangling Chen ◽  
Jiatian Lin ◽  
Qiaoling Chen ◽  
Ximian Liao ◽  
Tongyu Wang ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Transcription Initiation ◽  
Cox Regression ◽  
Clear Cell ◽  
The Cancer Genome Atlas ◽  
Migration Ability ◽  
Cell Renal Cell Carcinoma ◽  
Expression Levels

Metastasis is the main cause of clear cell renal cell carcinoma (ccRCC) treatment failure, and the key genes involved in ccRCC metastasis remain largely unknown. We analyzed the ccRCC datasets in The Cancer Genome Atlas database, comparing primary and metastatic ccRCC tumor records in search of tumor metastasis–associated genes, and then carried out overall survival, Cox regression, and receiver operating characteristic (ROC) analyses to obtain potential prognostic markers. Comprehensive bioinformatics analysis was performed to verify that the checkpoint with forkhead associated and ring finger domains (CHFR) gene is a reliable candidate oncogene, which is overexpressed in ccRCC metastatic tumor tissue, and that high expression levels of CHFR indicate a poor prognosis. A detailed analysis of the methylation of CHFR in ccRCC tumors showed that three sites within 200 bp of the transcription initiation site were significantly associated with prognosis and that hypomethylation was associated with increased CHFR gene expression levels. Knockdown of CHFR in ccRCC cells inhibited cell proliferation, colony formation, and migration ability. In summary, our findings suggest that the epigenetic signature on CHFR gene is a novel prognostic feature; furthermore, our findings offer theoretical support for the study of metastasis-related genes in ccRCC and provided new insights for the clinical treatment of the disease.

scholarly journals A novel 10 glycolysis-related genes signature could predict overall survival for clear cell renal cell carcinoma

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Qianwei Xing ◽  
Tengyue Zeng ◽  
Shouyong Liu ◽  
Hong Cheng ◽  
Limin Ma ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Cox Regression ◽  
Clear Cell ◽  
Low Risk ◽  
The Cancer Genome Atlas ◽  
Regression Analyses ◽  
Cell Renal Cell Carcinoma

Abstract Background The role of glycolysis in tumorigenesis has received increasing attention and multiple glycolysis-related genes (GRGs) have been proven to be associated with tumor metastasis. Hence, we aimed to construct a prognostic signature based on GRGs for clear cell renal cell carcinoma (ccRCC) and to explore its relationships with immune infiltration. Methods Clinical information and RNA-sequencing data of ccRCC were obtained from The Cancer Genome Atlas (TCGA) and ArrayExpress datasets. Key GRGs were finally selected through univariate COX, LASSO and multivariate COX regression analyses. External and internal verifications were further carried out to verify our established signature. Results Finally, 10 GRGs including ANKZF1, CD44, CHST6, HS6ST2, IDUA, KIF20A, NDST3, PLOD2, VCAN, FBP1 were selected out and utilized to establish a novel signature. Compared with the low-risk group, ccRCC patients in high-risk groups showed a lower overall survival (OS) rate (P = 5.548Ee-13) and its AUCs based on our established signature were all above 0.70. Univariate/multivariate Cox regression analyses further proved that this signature could serve as an independent prognostic factor (all P < 0.05). Moreover, prognostic nomograms were also created to find out the associations between the established signature, clinical factors and OS for ccRCC in both the TCGA and ArrayExpress cohorts. All results remained consistent after external and internal verification. Besides, nine out of 21 tumor-infiltrating immune cells (TIICs) were highly related to high- and low- risk ccRCC patients stratified by our established signature. Conclusions A novel signature based on 10 prognostic GRGs was successfully established and verified externally and internally for predicting OS of ccRCC, helping clinicians better and more intuitively predict patients’ survival.

A robust ferroptosis-related gene signature predicts overall survival in clear cell renal cell carcinoma

2021 ◽  
Author(s):  
Li Canxuan ◽  
Long Dan
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Cox Regression ◽  
Clear Cell ◽  
Risk Groups ◽  
Gene Signature ◽  
The Cancer Genome Atlas ◽  
Entire Group ◽  
Cell Renal Cell Carcinoma

Aims: To investigate the prognostic values and potential mechanisms of ferroptosis-related genes in clear cell renal cell carcinoma. Methods: Univariate Cox, least absolute shrinkage and selection operator regression and multivariate Cox regression analyses were employed to identify prognosis-related hub ferroptosis-related genes and establish a prognostic model. Results: The authors established a novel clinical predictive model based on seven hub ferroptosis-related genes in The Cancer Genome Atlas training cohort (n = 374) that was verified in the testing cohort (n = 156) and the entire group (n = 530). Functional analysis indicated that several carcinogenic pathways were enriched. Tumor-infiltrating cells and immunosuppressive molecules were significantly different between the two risk groups. Conclusion: Collectively, the authors successfully constructed a novel ferroptosis-related risk signature that was significantly associated with the prognosis of clear cell renal cell carcinoma.

scholarly journals Epigenetic signature predicts overall survival clear cell renal cell carcinoma

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Yejinpeng Wang ◽  
Liang Chen ◽  
Lingao Ju ◽  
Kaiyu Qian ◽  
Xinghuan Wang ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Cox Regression ◽  
Clear Cell ◽  
The Cancer Genome Atlas ◽  
Cell Renal Cell Carcinoma ◽  
Cox Regression Analysis

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.

scholarly journals Identification of a three-m6A related gene risk score model as a potential prognostic biomarker in clear cell renal cell carcinoma

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e8827 ◽  
Author(s):  
Yiqiao Zhao ◽  
Zijia Tao ◽  
Xiaonan Chen
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Risk Score ◽  
Renal Cell ◽  
Cox Regression ◽  
Clear Cell ◽  
Experimental Studies ◽  
The Cancer Genome Atlas ◽  
Cell Renal Cell Carcinoma ◽  
Cox Regression Analysis

Background Clear cell renal cell carcinoma (ccRCC) is one of the most prevalent malignancies worldwide, N6-methyladenosine (m6A) has been shown to play important roles in regulating gene expression and phenotypes in both health and disease. Here, our purpose is to construct a m6A-regulrator-based risk score (RS) for prediction of the prognosis of ccRCC. Methods We used clinical and expression data of m6A related genes from The Cancer Genome Atlas (TCGA) dataset and the Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression analysis to develop an RS to predict survival of patients with ccRCC, and analyzed correlations between RS and other clinical indicators such as age, grade and stage. Validation of this RS was then engaged in another cohort, E-MTAB-1980 from the ArrayExpress dataset. Finally, we used quantitative real-time PCR to analyze the expression profile of genes consists of the RS. Results A three-gene RS including METTL3, METTL14 and HNRNPA2B1 which can predict overall survival (OS) of ccRCC patients from TCGA. After applying this RS into the validation cohort from Arrayexpress, we found that it successfully reproduced the result; furthermore, the results of PCR validation were in line with our analysis. Conclusion To sum up, our study has identified an RS composed of m6A related genes that may predict the prognosis of ccRCC patients, which might be helpful for future therapeutic strategies. Our results call for further experimental studies for validations.

scholarly journals Identification of Six Potentially Long Noncoding RNAs as Biomarkers Involved Competitive Endogenous RNA in Clear Cell Renal Cell Carcinoma

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Kang Yang ◽  
Xiao-fan Lu ◽  
Peng-cheng Luo ◽  
Jie Zhang
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Expression Profiles ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
The Cancer Genome Atlas ◽  
Cell Renal Cell Carcinoma ◽  
Cerna Network

Background. Clear cell renal cell carcinoma (ccRCC), the most common subtype of renal cell carcinoma (RCC), usually is representative of metastatic heterogeneous neoplasm that links with poor prognosis, but the pathogenesis of ccRCC remains unclear. Currently, numerous evidences prove that long noncoding RNAs (lncRNAs) are considered as competing endogenous RNA (ceRNA) to participate in cellular processes of tumors. Therefore, to investigate the underlying mechanisms of ccRCC, the expression profiles of lncRNAs, miRNAs, and mRNAs were downloaded from the Cancer Genome Atlas (TCGA) database. A total of 1526 differentially expressed lncRNAs (DElncRNAs), 54 DEmiRNAs, and 2352 DEmRNAs were identified. To determine the connection of them, all DElncRNAs were input to the miRcode database. The results indicated that 85 DElncRNAs could connect with 9 DEmiRNAs in relation to our study. Then, databases of TargetScan and miRDB were used to search for targeted genes with reference to DEmiRNAs. The results showed that 203 out of 2352 targeted genes were identified in our TCGA set. Subsequently, ceRNA network was constructed according to Cytoscape and the targeted genes were functionally analyzed to elucidate the mechanisms of DEmRNAs. The results of survival analysis and regression analysis indicated that 6 DElncRNAs named COL18A1-AS1, WT1-AS, LINC00443, TCL6, AL356356.1, and SLC25A5-AS1 were significantly correlative with the clinical traits of ccRCC patients and could be served as predictors for ccRCC. Finally, these findings were validated by quantitative RT-PCR (qRT-PCR). Based on these discoveries, we believe that this identified ceRNA network will provide a novel perspective to elucidate ccRCC pathogenesis.

scholarly journals Combination of expression levels of miR-21 and miR-126 is associated with cancer-specific survival in clear-cell renal cell carcinoma

BMC Cancer ◽  
2014 ◽  
Vol 14 (1) ◽  
Author(s):  
Daniel Vergho ◽  
Susanne Kneitz ◽  
Andreas Rosenwald ◽  
Charlotte Scherer ◽  
Martin Spahn ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma ◽  
Cancer Specific Survival ◽  
Expression Levels

A prognostic nomogram based on competing endogenous RNA network for clear-cell renal cell carcinoma

2020 ◽  
Author(s):  
Yun Peng ◽  
Shangrong Wu ◽  
Zihan Xu ◽  
Dingkun Hou ◽  
Nan Li ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Rna Sequencing ◽  
Renal Cell ◽  
Cox Regression ◽  
Clear Cell ◽  
Gene Signature ◽  
Expression Data ◽  
Competing Endogenous Rna ◽  
Cell Renal Cell Carcinoma

Abstract Backgroud Clear-cell renal cell carcinoma (ccRCC) is stubborn to traditional chemotherapy and radiation treatment, which makes its clinical management a major challenge. Recently, we have made efforts to understand the etiology of ccRCC. Increasing evidence revealed that the competing endogenous RNA (ceRNA) were involved in the development of various tumor. However, it’s scant for studying on ccRCC, and a comprehensive analysis of prognostic model based on lncRNA-miRNA-mRNA ceRNA regulatory network of ccRCC with large-scale sample size and RNA‐sequencing expression data is still limited. Methods RNA‐sequencing expression data were taken out from GTEx database and TCGA database, A total of 354 samples with ccRCC and 157 normal controlled samples were included in our study. The ccRCC-specific genes were obtained from WGCNA and differential expression analysis. Following, the communication between mRNAs and lncRNAs and target miRNAs were predicted by MiRcode, starBase, miRTarBase, and TargetScan. A gene signature of eight genes was constructed by univariate Cox regression, lasso methods and multivariate Cox regression analysis. Results A total of 2191 mRNAs and 1377 lncRNAs was identified, and a dys-regulated ceRNA network for ccRCC was established using 7 mRNAs, 363 lncRNAs, and 3 miRNAs. Further, a gene signature in cluding 8 genes based on this ceRNA was constructed, meanwhile, a nomogram predicting 1-, 3-, 5-year survival probability containing both clinical characteristics and ccRCC-specific gene signatures was developed. Conclusion It could contribute to a better understanding of ccRCC tumorigenesis mechanism and guide clinicians to make a more accurate treatment decision.

scholarly journals Long Non-Coding RNA LINC02747 Promotes the Proliferation of Clear Cell Renal Cell Carcinoma by Inhibiting miR-608 and Activating TFE3

2020 ◽  
Vol 10 ◽  
Author(s):  
Xiang Ju ◽  
Yangyang Sun ◽  
Feng Zhang ◽  
Xiaohui Wei ◽  
Zhenguo Wang ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Histological Grade ◽  
Rapid Development ◽  
The Cancer Genome Atlas ◽  
Cell Renal Cell Carcinoma

With the rapid development of biotechnology, long noncoding RNAs (lncRNAs) have exhibited good application prospects in the treatment of cancer, and they may become new treatment targets for cancer. This study aimed to explore lncRNAs in clear cell renal cell carcinoma (ccRCC). Differentially expressed lncRNAs in 54 pairs of ccRCC tissues and para-carcinoma tissues were analyzed in The Cancer Genome Atlas (TCGA), and the most significant lncRNAs were selected and verified in ccRCC tissues. We found that lncRNA LINC02747 was highly expressed in ccRCC (P &lt; 0.001) and was closely related to high TNM stage (P = 0.006) and histological grade (P = 0.004) and poor prognosis of patients (P &lt; 0.001). In vivo and in vitro experiments confirmed that LINC02747 could promote the proliferation of ccRCC cells. We also found that LINC02747 regulated the proliferation of RCC cells by adsorbing miR-608. Subsequent mechanistic research showed that miR-608 is downregulated in ccRCC (P &lt; 0.001), and overexpression of miR-608 inbibited the proliferation of RCC cells. Moreover, we found that TFE3 is a direct target gene of miR-608. MiR-608 regulated the proliferation of RCC cells by inhibiting TFE3. In conclusion, LINC02747 upregulates the expression of TFE3 by adsorbing miR-608, ultimately promoting the proliferation of ccRCC cells. The above findings indicate that LINC02747 acts as an oncogene in ccRCC and may be developed as a molecular marker for the diagnosis and prognosis of ccRCC. The LINC02747/miR-608/TFE3 pathway may become a new therapeutic target for ccRCC.

scholarly journals Expression and clinical significance of PTPN12 in clear cell renal cell carcinoma

2020 ◽  
Vol 48 (12) ◽  
pp. 030006052093604
Author(s):  
Yi Jin ◽  
Tian-xi Wang ◽  
Hao Li ◽  
Peng Guo ◽  
Qing-qing Wang
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Mrna Expression ◽  
Renal Cell ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma ◽  
Expression Levels ◽  
Relative Expression ◽  
Normal Tissues ◽  
Mrna Expression Levels

Background Clear cell renal cell carcinoma (ccRCC) is a common urological disease. Expression of the protein tyrosine phosphatase 12 gene ( PTPN12) is decreased in many cancers; however, the relationship between PTPN12 gene function and renal cancer remains unclear. Methods We detected PTPN12 protein expression in ccRCC and corresponding normal tissues from 64 patients with ccRCC by immunohistochemistry, and relative PTPN12 mRNA levels by real-time quantitative polymerase chain reaction. The relationships between the relative expression levels of PTPN12 mRNA and the patients’ clinical data were analyzed. Results PTPN12 protein and mRNA expression levels were significantly lower in ccRCC compared with the corresponding normal tissues. The mRNA expression levels in the ccRCC and corresponding normal tissues from the 64 patients with ccRCC were 0.459±0.445 and 1.001±0.128, respectively, compared with the control (glyceraldehyde 3-phosphate dehydrogenase). There was a significant correlation between relative expression of PTPN12 mRNA in ccRCC tissues and tumor diameter and clinical stage. Conclusion The expression levels of PTPN12 protein and mRNA were significantly lower in ccRCC tissues compared with normal tissues. The role of PTPN12 may provide new insights and evidence to aid the diagnosis and targeted therapy of ccRCC.

scholarly journals Long Noncoding RNA HOTTIP Serves as an Independent Predictive Biomarker for the Prognosis of Patients with Clear Cell Renal Cell Carcinoma

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Zhanxin Liu ◽  
Zichun Wang ◽  
Xiaoxiong Wang ◽  
Meisong Lu ◽  
Guang Chen
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Noncoding Rna ◽  
Clear Cell ◽  
Clinical Stage ◽  
Predictive Biomarker ◽  
The Cancer Genome Atlas ◽  
Cell Renal Cell Carcinoma ◽  
Advanced Clinical Stage

Several studies have indicated that HOXA transcript at the distal tip (HOTTIP) play important roles in the tumorigenesis and development of various cancers. We aim to investigate the expression and prognostic value of HOTTIP in clear cell renal cell carcinoma (ccRCC). A systematic review of PubMed, Embase, Medline, and Web of Science databases was performed to select eligible literatures relevant to the correlation between HOTTIP expression and clinical outcome of different cancers. The association between the HOTTIP level and overall survival (OS), lymph node metastasis (LNM), or clinical stage was subsequently analyzed. Survival analyses were performed in a large cohort of more than 500 patients with ccRCC from The Cancer Genome Atlas (TCGA) using bioinformatic methods. Seventeen studies with a total of 1594 patients with thirteen kinds of carcinomas were included in this analysis. The result showed that high HOTTIP expression could predict worse outcome in cancer patients, with the pooled hazard ratio (HR) of 2.34 (95% confidence interval (CI) 1.96–2.79, p<0.0001). The result also showed that elevated HOTTIP expression was correlated with more LNM (OR=2.61, 95% CI 1.91-3.58, p<0.0001) and advanced clinical stage (OR=3.57, 95% CI 2.58-4.93, p<0.0001). We further validated that ccRCC patients with higher HOTTIP expression tend to have unsatisfactory outcomes both in the entire TCGA dataset and different clinical stratums, like age, grade, and stage. The tumor of those patients was associated with a larger size, easier to metastasis, advanced clinical stage, and a higher pathological grade. These findings suggested that increased HOTTIP expression might act as a novel prognostic marker for ccRCC patients.

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