scholarly journals Identification of biomarkers and construction of a microRNA‑mRNA regulatory network for clear cell renal cell carcinoma using integrated bioinformatics analysis

PLoS ONE ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. e0244394
Author(s):  
Miaoru Han ◽  
Haifeng Yan ◽  
Kang Yang ◽  
Boya Fan ◽  
Panying Liu ◽  
...  

With the recent research development, the importance of microRNAs (miRNAs) in renal clear cell carcinoma (CCRCC) has become widely known. The purpose of this study is to screen out the potential biomarkers of renal clear cell carcinoma (CCRCC) by microarray analysis. The miRNA chip (GSE16441) and mRNA chip (GSE66270) related to CCRCC were downloaded from the Gene Expression Omnibus (GEO) database. After data filtering and pretreating, R platform and a series of analysis tools (funrich3.1.3, string, Cytoscape_ 3.2.1, David, etc.) were used to analyze chip data and identify the specific and highly sensitive biomarkers. Finally, by constructing the miRNA -mRNA interaction network, it was determined that five miRNAs (hsa-mir-199a-5p, hsa-mir-199b-5p, hsa-mir-532-3p and hsa-mir-429) and two key genes (ETS1 and hapln1) are significantly related to the overall survival rate of patients.

2019 ◽  
Vol 15 (27) ◽  
pp. 3103-3110 ◽  
Author(s):  
Longxiang Xie ◽  
Qiang Wang ◽  
Yifang Dang ◽  
Linna Ge ◽  
Xiaoxiao Sun ◽  
...  

Aim: To develop a free and quick analysis online tool that allows users to easily investigate the prognostic potencies of interesting genes in kidney renal clear cell carcinoma (KIRC). Patients & methods: A total of 629 KIRC cases with gene expression profiling data and clinical follow-up information are collected from public Gene Expression Omnibus and The Cancer Genome Atlas databases. Results: One web application called Online consensus Survival analysis for KIRC (OSkirc) that can be used for exploring the prognostic implications of interesting genes in KIRC was constructed. By OSkirc, users could simply input the gene symbol to receive the Kaplan–Meier survival plot with hazard ratio and log-rank p-value. Conclusion: OSkirc is extremely valuable for basic and translational researchers to screen and validate the prognostic potencies of genes for KIRC, publicly accessible at http://bioinfo.henu.edu.cn/KIRC/KIRCList.jsp


Genes ◽  
2020 ◽  
Vol 11 (4) ◽  
pp. 440
Author(s):  
Yitong Zhang ◽  
Jiaxing Wang ◽  
Xiqing Liu

Kidney renal clear cell carcinoma (KIRC) is the most common and fatal subtype of renal cancer. Antagonistic associations between selenium and cancer have been reported in previous studies. Selenium compounds, as anti-cancer agents, have been reported and approved for clinical trials. The main active form of selenium in selenoproteins is selenocysteine (Sec). The process of Sec biosynthesis and incorporation into selenoproteins plays a significant role in biological processes, including anti-carcinogenesis. However, a comprehensive selenoprotein mRNA analysis in KIRC remains absent. In the present study, we examined all 25 selenoproteins and identified key selenoproteins, glutathione peroxidase 3 (GPX3) and type 1 iodothyronine deiodinase (DIO1), with the associated prognostic biomarker leucine-rich repeat containing 19 (LRRC19) in clear cell renal cell carcinoma cases from The Cancer Genome Atlas (TCGA) database. We performed validations for the key gene expression levels by two individual clear cell renal cell carcinoma cohorts, GSE781 and GSE6344, datasets from the Gene Expression Omnibus (GEO) database. Multivariate survival analysis demonstrated that low expression of LRRC19 was an independent risk factor for OS. Gene set enrichment analysis (GSEA) identified tyrosine metabolism, metabolic pathways, peroxisome, and fatty acid degradation as differentially enriched with the high LRRC19 expression in KIRC cases, which are involved in selenium therapy of clear cell renal cell carcinoma. In conclusion, low expression of LRRC19 was identified as an independent risk factor, which will advance our understanding concerning the selenium adjuvant therapy of clear cell renal cell carcinoma.


PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e10848
Author(s):  
Ninghua Wang ◽  
Jing Yuan ◽  
Fei Liu ◽  
Jun Wei ◽  
Yu Liu ◽  
...  

Kidney renal clear cell carcinoma (KIRC) is the most common and aggressive type of renal cell carcinoma. Due to high mortality rate, high metastasis rate and chemical resistance, the prognosis of KIRC patients is poor. Therefore, it is necessary to study the mechanisms of KIRC development and to develop more effective prognostic molecular biomarkers to help clinical patients. In our study, we used The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases to investigate that the expression of nuclear factor I B (NFIB) is significantly higher in KIRC than in adjacent tissues. Moreover, NFIB expression levels are associated with multiple clinical pathological parameters of KIRC, and KIRC patients with high NFIB expression have poor prognosis, suggesting that NFIB may play vital roles in the malignant development of KIRC. Further studies demonstrated that NFIB could promote the progression and metastasis of KIRC and participate in the regulation of PTEN induced kinase 1 (PINK1). Furthermore, we used chromatin immunoprecipitation (ChIP) experiments to confirm that NFIB binds to the PINK1 promoter and regulates its expression at the transcriptional level. Further experiments also confirmed the important roles of PINK1 in promoting the development of tumors by NFIB. Hence, our data provide a new NFIB-mediated regulatory mechanism for the tumor progression of KIRC and suggest that NFIB can be applied as a new predictor and therapeutic target for KIRC.


2021 ◽  
Vol 10 ◽  
Author(s):  
Jianhong Zhao ◽  
Jiangpeng Wu ◽  
Jinyan Wei ◽  
Xiaolu Su ◽  
Yanjun Chai ◽  
...  

Currently, preoperative diagnosis and differentiation of renal clear cell carcinoma and other subtypes remain a serious challenge for doctors. The liquid biopsy technique and artificial intelligence have inspired the pursuit of distinguishing clear cell renal cell carcinoma using clinically available test data. In this work, a method called liq_ccRCC based on the integration of clinical blood and urine indices through machine learning approaches was successfully designed to achieve this goal. Clinically available biochemical blood data and urine indices were collected from 306 patients with renal cell carcinoma. Finally, the integration of 18 top-ranked clinical liquid indices (13 blood samples and 5 urine samples) was proven to be able to distinguish renal clear cell carcinoma from other subtypes of renal carcinoma by cross-valuation with an AUC of 0.9372. The successful introduction of this identification method suggests that subtype differentiation of renal cell carcinoma can be accomplished based on clinical liquid test data, which is noninvasive and easy to perform. It has huge potential to be developed as a promising innovation strategy for preoperative subtype differentiation of renal cell carcinoma with the advantages of convenience and real-time testing. liq_ccRCC is available online for the free test of readers at http://lishuyan.lzu.edu.cn/liq_ccRCC.


2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Qian Wang ◽  
Hao Zhang ◽  
Quanbing Chen ◽  
Zhenghua Wan ◽  
Xiaoyong Gao ◽  
...  

The kidney renal clear cell carcinoma (KIRC) with poor prognosis is the main histological subtype of the renal cell carcinoma, accounting for 80–90% of patients. Currently, the N6-methyladenosine (m6A) epitranscriptional modification draws much attention. The m6A RNA modification, the most plentiful internal modification of mRNAs and noncoding RNAs in the majority of eukaryotes, regulates mRNAs at different levels and is involved in disease occurrence and progression. The GTExPortal and TCGAportal were applied to investigate the METTL14 mRNA expression in different tissues and KIRC stages. The Human Protein Atlas was used to verify the location of METTL14 in KIRC tissues. The main microRNAs (miRNAs) related to KIRC were analyzed using OncoLnc and starBase, while corresponding circular RNAs (circRNAs) interacting with miRNAs were predicted via circBank; then, the METTL14-miRNA-circRNA interaction network was established. The level of methyltransferase-like 14 (METTL14) mRNA was significantly lower in KIRC tissues compared with normal kidney tissues, which was relative to clinical and pathological stages. circRNAs may regulate METTL14 mRNA as miRNAs sponge to affect the KIRC progression. METTL14 mRNA is likely to regulate PTEN mRNA expression via changing its m6A RNA modification level. METTL14 mRNA expression negatively correlated with the KIRC stages and positively correlated with KIRC patients’ overall survival, which has great potential to serve as a clinical biomarker in KIRC.


2022 ◽  
Author(s):  
Fu Liu ◽  
Xinyuan Li ◽  
Xiang Zhou ◽  
Hang Tong ◽  
Xin Gou

Abstract Background: Renal cell carcinoma is the most common aggressive tumor of the genitourinary system. The main pathological subtype is clear cell renal cell carcinoma (ccRCC), and its treatment options are very limited. Therefore, identifying specific markers of renal clear cell carcinoma is of great significance for diagnosis and prognosis.Methods: From the TCGA database, we obtained information on 611 patients with renal clear cell carcinoma to analyze the relationship between hypoxia-related lncRNAs and overall survival. According to the coexpression of hypoxia genes and lncRNAs, genes related to hypoxia were identified. Difference analysis and Cox regression analysis were applied to assess survival-related risk factors. According to the median risk score of hypoxia-related genes, patients were divided into high-risk and low-risk groups. According to these gene characteristics and clinical parameters, a nomogram map was built, and GSEA was used for gene function annotation. RT-qRCR, Western Blot and Flow Cytometry were used to determine the role of SNHG19 in RCC cells.Results: By analyzing the coexpression of hypoxia genes and lncRNAs, 310 hypoxia-related genes were obtained. Six sHRlncRs were significantly correlated with the clinical outcomes of patients with ccRCC. Four sHRlncRs (AC011445.2, PTOV1-AS2, AP004609.3, and SNHG19) with the highest prognostic values were included in the group to construct the HRRS model. The high-risk group had a shorter OS than the low-risk group. HR-lncRNAs were considered to be an independent prognostic factor and associated with OS. The high- and low-risk groups showed different pathways in GSEA. Experiments showed that SNHG19 plays essential roles in autophagy and apoptosis of RCC cells.Conclusion: Our research shows that we established and verified a hypoxia-related lncRNA model that accurately correlates with ccRCC patients. This study also provides novel insights into hypoxia-based mechanisms and provides new biomarkers for the poor prognosis of ccRCC patients.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Tongjun Gu ◽  
Xiwu Zhao

Abstract Clear cell renal cell carcinoma (ccRCC) is highly heterogeneous and is the most lethal cancer of all urologic cancers. We developed an unsupervised deep learning method, stacked denoising autoencoders (SdA), by integrating multi-platform genomic data for subtyping ccRCC with the goal of assisting diagnosis, personalized treatments and prognosis. We successfully found two subtypes of ccRCC using five genomics datasets for Kidney Renal Clear Cell Carcinoma (KIRC) from The Cancer Genome Atlas (TCGA). Correlation analysis between the last reconstructed input and the original input data showed that all the five types of genomic data positively contribute to the identification of the subtypes. The first subtype of patients had significantly lower survival probability, higher grade on neoplasm histology and higher stage on pathology than the other subtype of patients. Furthermore, we identified a set of genes, proteins and miRNAs that were differential expressed (DE) between the two subtypes. The function annotation of the DE genes from pathway analysis matches the clinical features. Importantly, we applied the model learned from KIRC as a pre-trained model to two independent datasets from TCGA, Lung Adenocarcinoma (LUAD) dataset and Low Grade Glioma (LGG), and the model stratified the LUAD and LGG patients into clinical associated subtypes. The successful application of our method to independent groups of patients supports that the SdA method and the model learned from KIRC are effective on subtyping cancer patients and most likely can be used on other similar tasks. We supplied the source code and the models to assist similar studies at https://github.com/tjgu/cancer_subtyping.


PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9453
Author(s):  
Mingzhe Jiang ◽  
Jiaxing Lin ◽  
Haotian Xing ◽  
Jun An ◽  
Jieping Yang ◽  
...  

Background Kidney renal clear cell carcinoma (KIRC) affects the genitourinary system. Although treatment of KIRC in early stages can be highly successful, this type of cancer is difficult to detect until later stages of disease that are less easily treatable. Previous studies have focused on tumor cells, but have ignored the contributions of the tumor microenvironment. Methods We analyzed KIRC gene expression data from The Cancer Genome Atlas with the ESTIMATE algorithm to identify differentially expressed genes. Through protein–protein interaction network analysis, we identified clusters and picked genes from the clusters for further analysis. Differential expression, Kaplan–Meier, and univariate Cox analyses were used to select prognostic biomarkers. Gene Set Enrichment Analysis (GSEA) and Tumor Immune Estimation Resource (TIMER) analysis were used to explore the immune characteristics of these genes as biomarkers. Results Through the ESTIMATE algorithm and other system biology tools, TNFSF13B was identified as a prognostic biomarker. TNFSF13B is highly expressed in tumors, and high expression of TNFSF13B leads to poor prognosis. Further GSEA and TIMER analysis revealed that the expression of TNFSF13B was related to the immune signaling pathway and lymphocyte infiltration. Our findings strongly suggest that TNFSF13B may be a potential biomarker or target related to the tumor microenvironment for KIRC.


2013 ◽  
Vol 13 (2) ◽  
pp. 79-80
Author(s):  
Zane Simtniece ◽  
Gatis Kirsakmens ◽  
Ilze Strumfa ◽  
Andrejs Vanags ◽  
Maris Pavars ◽  
...  

Abstract Here, we report surgical treatment of a patient presenting with pancreatic metastasis (MTS) of renal clear cell carcinoma (RCC) 11 years after nephrectomy. RCC is one of few cancers that metastasise in pancreas. Jaundice, abdominal pain or gastrointestinal bleeding can develop; however, asymptomatic MTS can be discovered by follow-up after removal of the primary tumour. The patient, 67-year-old female was radiologically diagnosed with a clinically silent mass in the pancreatic body and underwent distal pancreatic resection. The postoperative period was smooth. Four months after the surgery, there were no signs of disease progression.


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