scholarly journals Identification of a Gene Signature for Renal Cell Carcinoma–Associated Fibroblasts Mediating Cancer Progression and Affecting Prognosis

2021 ◽  
Vol 8 ◽  
Author(s):  
Bitian Liu ◽  
Xiaonan Chen ◽  
Yunhong Zhan ◽  
Bin Wu ◽  
Shen Pan
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cancer Progression ◽  
Renal Cell ◽  
Gene Signature ◽  
Clinicopathological Parameters ◽  
Advanced Tumor Stage ◽  
Advanced Tumor ◽  
Potential Biomarker ◽  
Key Genes

Background: Cancer-associated fibroblasts (CAFs) are mainly involved in cancer progression and treatment failure. However, the specific signature of CAFs and their related clinicopathological parameters in renal cell carcinoma (RCC) remain unclear. Here, methods to recognize gene signatures were employed to roughly assess the infiltration of CAFs in RCC, based on the data from The Cancer Genome Atlas (TCGA). Weighted Gene Coexpression Network Analysis (WGCNA) was used to cluster transcriptomes and correlate with CAFs to identify the gene signature. Single-cell and cell line sequencing data were used to verify the expression specificity of the gene signature in CAFs. The gene signature was used to evaluate the infiltration of CAFs in each sample, and the clinical significance of each key gene in the gene signature and CAFs was analyzed. We observed that the CAF infiltration was higher in kidney cancer and advanced tumor stage and grade than in normal tissues. The seven key genes of the CAF gene signature identified using WGCNA showed high expression of CAF-related characteristics in the cell clustering landscape and fibroblast cell lines; these genes were found to be associated with extracellular matrix function, collagen synthesis, cell surface interaction, and adhesion. The high CAF infiltration and the key genes were verified from the TCGA and Gene Expression Omnibus data related to the advanced grade, advanced stage, and poor prognosis of RCC. In summary, our findings indicate that the clinically significant gene signature may serve as a potential biomarker of CAFs in RCC, and the infiltration of CAFs is associated with the pathological grade, stage, and prognosis of RCC.

scholarly journals Identification Of Gene Signature For Renal Cell Carcinoma-Associated Fibroblasts Mediating Cancer Progression And Affecting Prognosis

2020 ◽  
Author(s):  
Bitian Liu ◽  
Xiaonan Chen ◽  
Yunhong Zhan ◽  
Bin Wu ◽  
Shen Pan
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Single Cell ◽  
Clinical Significance ◽  
Cell Lines ◽  
Cancer Progression ◽  
Renal Cell ◽  
Gene Signature ◽  
Pathological Grade ◽  
Single Cell Sequencing

Abstract Background: Cancer-associated fibroblasts (CAFs) are most abundant in stroma and are critically involved in cancer progression. However, the specific signature of CAFs and related clinicopathological parameters in renal cell carcinoma (RCC) remain unclear. Methods: In this work, methods using recognized gene signatures were employed to roughly assess the infiltration level of the stroma and CAFs in RCC based on the data in The Cancer Genome Atlas. Weighted gene co-expression network analysis (WGCNA) was used to cluster transcriptomes and correlate with CAFs to identify specific markers. A comparison of fibroblast versus urothelial carcinoma cell lines and correlation with previously reported CAF markers were performed to demonstrate the specific expressed of the gene signature. The gene signature was used to compare fibroblast infiltration of each sample through single sample gene set enrichment analysis, and the clinical significance of fibroblasts was analyzed via Cox risk assessment and the chi-square test. Finally, we used validation data to verify the clinical significance of the fibroblast gene signature in RCC. Results: Roughly calculated tumor matrix and CAF levels were significantly higher in kidney cancer than in normal tissues. More than 85% of fibroblast-specific markers identified by WGCNA were consistent with markers obtained via single-cell sequencing. These markers were more highly expressed in fibroblast cell lines and were significantly correlated with canonical CAFs makers. Data validation also showed that CAFs were significant correlation with survival and pathological grade. Conclusions: In summary, our findings indicate that the gene signature potentially serves as a biomarker of CAFs in RCC and that infiltration of fibroblasts in RCC is an independent prognostic factor associated with pathological grade and stage of tumor. The ability to recognize specific CAF markers using WGCNA is comparable to single-cell sequencing.

scholarly journals Downregulation of the lncRNA ASB16-AS1 Decreases LARP1 Expression and Promotes Clear Cell Renal Cell Carcinoma Progression via miR-185-5p/miR-214-3p

2021 ◽  
Vol 10 ◽  
Author(s):  
Mingzi Li ◽  
Bingde Yin ◽  
Mulin Chen ◽  
Jingtao Peng ◽  
Xinyu Mu ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Noncoding Rna ◽  
Clear Cell ◽  
Therapeutic Targets ◽  
Luciferase Reporter ◽  
Advanced Tumor Stage ◽  
Cell Renal Cell Carcinoma ◽  
Advanced Tumor

Clear cell renal cell carcinoma (ccRCC) comprises approximately 75% of renal cell carcinomas, which is one of the most common and lethal urologic cancers, with poor quality of life for patients and is a huge economic burden to health care systems. It is imperative we find novel prognostic and therapeutic targets for ccRCC clinical intervention. In this study, we found that the expression of the long noncoding RNA (lncRNA) ASB16-AS1 was downregulated in ccRCC tissues compared with non-diseased tissues and was also associated with advanced tumor stage and larger tumors. By constructing cell and mouse models, it was found that downregulated lncRNA ASB16-AS1 enhanced cell proliferation, migration, invasion, and promoted tumor growth and metastasis. Furthermore, by performing bioinformatics analysis, biotinylated RNA pull-downs, AGO2-RIP, and luciferase reporter assays, our findings showed that downregulated ASB16-AS1 decreased La-related protein 1 (LARP1) expression by inhibiting miR-185-5p and miR-214-3p. Furthermore, it was found that overexpression of LARP1 reversed the promotive effects of downregulated ASB16-AS1 on ccRCC cellular progression. Our results revealed that downregulated ASB16-AS1 promotes ccRCC progression via a miR-185-5p-miR-214-3p-LARP1 pathway. We suggest that this pathway could be used to monitor prognosis and presents therapeutic targets for ccRCC clinical management.

scholarly journals LncRNA UCA1 promotes renal cell carcinoma proliferation through epigenetically repressing p21 expression and negatively regulating miR-495

Tumor Biology ◽  
2017 ◽  
Vol 39 (5) ◽  
pp. 101042831770163 ◽  
Author(s):  
Yun Lu ◽  
Wei-Gang Liu ◽  
Jia-Hui Lu ◽  
Zhi Jun Liu ◽  
Hai-Bin Li ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Proliferation ◽  
Urothelial Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Phase Cell ◽  
Luciferase Reporter ◽  
Advanced Tumor Stage ◽  
Advanced Tumor ◽  
Enhancer Of Zeste

Long non-coding RNAs have recently emerged as important regulators in the pathogenesis and progression of cancers. The long non-coding RNA urothelial carcinoma–associated 1 is reportedly upregulated and functions as an oncogene in some tumors. However, the role of urothelial carcinoma–associated 1 in renal cell carcinoma is not well elucidated so far. In this study, we found that urothelial carcinoma–associated 1 was overexpressed in renal cell carcinoma tissues compared with the adjacent normal tissues, and higher urothelial carcinoma–associated 1 expression levels were positively associated with advanced tumor stage and poor survival time in renal cell carcinoma patients. Further studies showed that knockdown of urothelial carcinoma–associated 1 suppressed renal cell carcinoma cell proliferation and S-phase cell number in vitro. Moreover, urothelial carcinoma–associated 1 was found to be associated with enhancer of zeste homolog 2, which suppressed p21 expression through histone methylation (H3K27me3) on p21 promoter. We also showed that knockdown of urothelial carcinoma–associated 1 increased the p21 protein expression through regulating enhancer of zeste homolog 2. In addition, bioinformatics analysis and dual-luciferase reporter assays confirmed that miR-495 was a target of urothelial carcinoma–associated 1 in renal cell carcinoma, and urothelial carcinoma–associated 1 promoted cell proliferation by negatively regulating miR-495. These findings illuminated that urothelial carcinoma–associated 1 promoted renal cell carcinoma progression through enhancer of zeste homolog 2 and interacted with miR-495. Overall, overexpression of urothelial carcinoma–associated 1 functions as an oncogene in renal cell carcinoma that may offer a novel therapeutic target for renal cell carcinoma patients.

scholarly journals Significance of Immunohistochemical Expression of Survivin in Renal Cell Carcinoma

2021 ◽  
Vol 6 (3) ◽  
pp. 201-205
Author(s):  
Maisa Hashem Mohammed ◽  
Nagwa Abd El-Sadek Ahmed
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Survivin Expression ◽  
Tumor Stage ◽  
Genetic Mutation ◽  
Malignant Neoplasms ◽  
Advanced Tumor Stage ◽  
Advanced Tumor ◽  
Apoptosis Protein

Background: Evasion of apoptosis is an essential alteration for cellular genetic mutation. Survivin is a member of inhibitor of apoptosis protein (IAP) family. Under normal conditions, Survivin is expressed in embryonic and fetal tissues and markedly diminished in mature, differentiated adult tissues. Survivin was found to be re-expressed in multiple solid and hematological human malignant neoplasms. The purpose of this study was to evaluate the expression of Survivin in renal cell carcinoma (RCC), and to find statistically significant associations between Survivin and the tested Clinicopathological parameters.Methods: 39 patients with RCCs who underwent nephrectomy were included in the study. From each RCC specimen, two tissue sections were obtained; one was stained by H&E stain to determine both RCC phenotype and Fuhrman’s nuclear grades. The second tissue section was immunohistochemically stained by anti-human Survivin antibody. Results: The study revealed statistically significant associations between Survivin expression in RCC specimens and RCC histological types (p =0.002), high tumor grade (p< 0.001) and advanced tumor stage (p< 0.001). Conclusion: The study revealed that Survivin is positively correlated to poorly differentiated RCCs with high Fuhrman’s nuclear grade and advanced tumor stage. 

scholarly journals Cryptic Promoter Activation Drives POU5F1 (OCT4) Expression in Renal Cell Carcinoma

2018 ◽  
Author(s):  
Kyle T. Siebenthall ◽  
Chris P. Miller ◽  
Jeff D. Vierstra ◽  
Julie Mathieu ◽  
Maria Tretiakova ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Transcriptome Profiling ◽  
Advanced Tumor Stage ◽  
Cryptic Promoter ◽  
Advanced Tumor ◽  
Hif Pathway

Transcriptional dysregulation drives cancer formation but the underlying mechanisms are still poorly understood. As a model system, we used renal cell carcinoma (RCC), the most common malignant kidney tumor which canonically activates the hypoxia-inducible transcription factor (HIF) pathway. We performed genome-wide chromatin accessibility and transcriptome profiling on paired tumor/normal samples and found that numerous transcription factors with a RCC-selective expression pattern also demonstrated evidence of HIF binding in the vicinity of their gene body. Some of these transcription factors influenced the tumor’s regulatory landscape, notably the stem cell transcription factor POU5F1 (OCT4). Unexpectedly, we discovered a HIF-pathway-responsive cryptic promoter embedded within a human-specific retroviral repeat element that drives POU5F1 expression in RCC via a novel transcript. Elevat POU5F1 expression levels were correlated with advanced tumor stage and poorer overall survival in RCC patients. Thus, integrated transcriptomic and epigenomic analysis of even a small number of primary patient samples revealed remarkably convergent shared regulatory landscapes and a novel mechanism for dysregulated expression of POU5F1 in RCC.

scholarly journals Development of a novel gene signature to predict prognosis and response to PD-1 blockade in clear cell renal cell carcinoma

2021 ◽  
Vol 10 (1) ◽  
pp. 1933332
Author(s):  
Xiaomao Yin ◽  
Zaoyu Wang ◽  
Jianfeng Wang ◽  
Yunze Xu ◽  
Wen Kong ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Gene Signature ◽  
Cell Renal Cell Carcinoma ◽  
Novel Gene

scholarly journals CMTM6 expression as a potential biomarker for immunotherapy in metastatic renal cell carcinoma

2021 ◽  
Author(s):  
Gennadi Tulchiner ◽  
Andrea Brunner ◽  
Manuela Schmidinger ◽  
Nina Staudacher ◽  
Jacob J. Orme ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Potential Biomarker

scholarly journals Metabolomic Analysis to Elucidate Mechanisms of Sunitinib Resistance in Renal Cell Carcinoma

Metabolites ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 1
Author(s):  
Tomonori Sato ◽  
Yoshihide Kawasaki ◽  
Masamitsu Maekawa ◽  
Shinya Takasaki ◽  
Kento Morozumi ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Energy Metabolism ◽  
Cell Carcinoma ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Progression ◽  
Renal Cell ◽  
Treatment Resistance ◽  
Tca Cycle ◽  
Glutamine Uptake

Metabolomics analysis possibly identifies new therapeutic targets in treatment resistance by measuring changes in metabolites accompanying cancer progression. We previously conducted a global metabolomics (G-Met) study of renal cell carcinoma (RCC) and identified metabolites that may be involved in sunitinib resistance in RCC. Here, we aimed to elucidate possible mechanisms of sunitinib resistance in RCC through intracellular metabolites. We established sunitinib-resistant and control RCC cell lines from tumor tissues of RCC cell (786-O)-injected mice. We also quantified characteristic metabolites identified in our G-Met study to compare intracellular metabolism between the two cell lines using liquid chromatography-mass spectrometry. The established sunitinib-resistant RCC cell line demonstrated significantly desuppressed protein kinase B (Akt) and mesenchymal-to-epithelial transition (MET) phosphorylation compared with the control RCC cell line under sunitinib exposure. Among identified metabolites, glutamine, glutamic acid, and α-KG (involved in glutamine uptake into the tricarboxylic acid (TCA) cycle for energy metabolism); fructose 6-phosphate, D-sedoheptulose 7-phosphate, and glucose 1-phosphate (involved in increased glycolysis and its intermediate metabolites); and glutathione and myoinositol (antioxidant effects) were significantly increased in the sunitinib-resistant RCC cell line. Particularly, glutamine transporter (SLC1A5) expression was significantly increased in sunitinib-resistant RCC cells compared with control cells. In this study, we demonstrated energy metabolism with glutamine uptake and glycolysis upregulation, as well as antioxidant activity, was also associated with sunitinib resistance in RCC cells.

Sign in / Sign up

Export Citation Format

Share Document