scholarly journals The SLC Family Are Candidate Diagnostic and Prognostic Biomarkers in Clear Cell Renal Cell Carcinoma

2020 ◽  
Vol 2020 ◽  
pp. 1-17 ◽  
Author(s):  
Weiting Kang ◽  
Meng Zhang ◽  
Qiang Wang ◽  
Da Gu ◽  
Zhilong Huang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Clinical Stage ◽  
Expression Patterns ◽  
Cancer Genome ◽  
Cell Renal Cell Carcinoma ◽  
Expression Levels

Clear cell renal cell carcinoma (ccRCC) is the most common lethal subtype of renal cancer, and changes in tumor metabolism play a key role in its development. Solute carriers (SLCs) are important in the transport of small molecules in humans, and defects in SLC transporters can lead to serious diseases. The expression patterns and prognostic values of SLC family transporters in the development of ccRCC are still unclear. The current study analyzed the expression levels of SLC family members and their correlation with prognosis in ccRCC patients with data from Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), The Cancer Genome Atlas (TCGA), cBioPortal, the Human Protein Atlas (HPA), the International Cancer Genome Consortium (ICGC), and the Gene Expression Omnibus (GEO). We found that the mRNA expression levels of SLC22A6, SLC22A7, SLC22A13, SLC25A4, SLC34A1, and SLC44A4 were significantly lower in ccRCC tissues than in normal tissues and the protein expression levels of SLC22A6, SLC22A7, SLC22A13, and SLC34A1 were also significantly lower. Except for SLC22A7, the expression levels of SLC22A6, SLC22A13, SLC25A4, SLC34A1, and SLC44A4 were correlated with the clinical stage of ccRCC patients. The lower the expression levels of SLC22A6, SLC22A13, SLC25A4, SLC34A1, and SLC44A4 were, the later the clinical stage of ccRCC patients was. Further experiments revealed that the expression levels of SLC22A6, SLC22A7, SLC22A13, SLC25A4, SLC34A1, and SLC44A4 were significantly associated with overall survival (OS) and disease-free survival (DFS) in ccRCC patients. High SLC22A6, SLC22A7, SLC22A13, SLC25A4, SLC34A1, and SLC44A4 expression predicted improved OS and DFS. Finally, GSE53757 and ICGC were used to revalidate the differential expression and clinical prognostic value. This study suggests that SLC22A6, SLC22A7, SLC22A13, SLC25A4, SLC34A1, and SLC44A4 may be potential targets for the clinical diagnosis, prognosis, and treatment of ccRCC patients.

scholarly journals Decreased CDKL2 Expression in Clear Cell Renal Cell Carcinoma Predicts Worse Overall Survival

2022 ◽  
Vol 8 ◽  
Author(s):  
Zhan Chen ◽  
Yan Lv ◽  
Lu He ◽  
Shunli Wu ◽  
Zhuang Wu
Keyword(s):  
Gene Expression ◽  
Renal Cell Carcinoma ◽  
T Cell ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Poor Prognosis ◽  
Clear Cell ◽  
Cancer Genome ◽  
Gene Set Enrichment Analysis ◽  
Cell Renal Cell Carcinoma

Background: Clear cell renal cell carcinoma (ccRCC) is the most frequent and lethal type of kidney cancer. Although differential expression of cyclin-dependent kinase-like 2 (CDKL2) has been reported to be associated with tumor progression in other cancers, its prognostic value, and potential mechanism in patients with ccRCC still remain unknown.Methods: Gene expression analysis was conducted using The Cancer Genome Atlas (TCGA), Gene Expression Omnibus, and International Cancer Genome Consortium databases. Further, clinicopathologic analysis; Kaplan–Meier survival analysis; weighted gene co-expression network analysis; gene set enrichment analysis; gene ontology enrichment; methylation; and immune infiltration analyses were performed using TCGA-kidney renal clear cell carcinoma profiles. CDKL2 translational levels were analyzed using The Human Protein Atlas database.Results:CDKL2 expression was decreased in ccRCC samples retrieved from the four databases. Gender, survival status, histologic grade, clinical stage, TNM classification, and tumor status were closely related to CDKL2 expression. In addition, CDKL2 downregulation was an independent prognostic factor for poor prognosis in multivariate analysis. Enrichment analyses using multiple tests revealed that CDKL2 is not just closely related to immune response but this association is highly correlated as well. Further, we found that CDKL2 expression was significantly correlated with the infiltration levels of T cell CD4 memory resting; monocytes; macrophages M0, M1, and M2; dendritic cells resting; mast cells resting; plasma cells; T cell CD8; and T cell regulatory.Conclusion: This is the first report to study the expression of CDKL2 in ccRCC, wherein we suggest that decreased CDKL2 expression is closely correlated with poor prognosis in ccRCC. We consider that CDKL2 is a novel and potential prognostic biomarker associated with immune infiltrates in ccRCC.

Categorization of gene expression subtypes in clear cell renal cell carcinoma with sarcomatoid features.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 519-519
Author(s):  
Shreyas Joshi ◽  
Suraj Peri ◽  
Eric A. Ross ◽  
Robert G. Uzzo ◽  
Alexander Kutikov ◽  
...  
Keyword(s):  
Gene Expression ◽  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Gene Expression Profiles ◽  
Gene Expression Patterns ◽  
Cell Renal Cell Carcinoma

519 Background: Presence of sarcomatoid features in Renal Cell Carcinoma (sRCC) tumors signals aggressive clinical behavior and poor prognosis compared to Clear Cell Renal Cell Carcinoma (ccRCC). However, the underlying gene expression patterns of sRCC are poorly understood. We sought to categorize ccRCC and sRCC gene expression subtypes and compare survival outcomes, as well as evaluate whether sRCC gene expression patterns are similar to non-renal sarcomas. Methods: We identified 511 ccRCC cases, of which 36 had a sarcomatoid component from The Cancer Genome Atlas. Enrichment analysis was used to measure associations between gene expression signatures for soft tissue sarcomas and expression profiles of sRCC and ccRCC cases measured by RNA-Seq. The resulting scores were used to identify distinct patient groups using K-means clustering. Overall survival (OS) was evaluated by Kaplan-Meier, log rank, and Cox regression methods. Results: Our analysis identified 4 distinct clusters that differ in enrichment for soft-tissue sarcoma gene expression profiles. The clusters showed significantly different OS distributions (p-value<0.001 log rank). Most sRCC cases (69%) segregated into a single cluster with the worst prognosis. Among ccRCC cases, 57% of patients with higher levels of sarcoma signature enrichment were associated with a shorter OS, which is independent of tumor stage. 5-year/median OS survival estimates for ccRCC cases in the 4 clusters, by increasing levels of sarcoma profile enrichment, were 83%/NR, 75%/NR, 67%/90.9 mo, and 49%/56.7 mo. We also validated existence of these clusters in another sRCC cohort (Sircar 2015). Conclusions: We identified strong associations between sarcoma expression signatures and gene expression profiles of sRCC. We also found that 57% of morphologically non-sRCC cases demonstrate enrichment for sarcoma expression signatures, and these patients have worse OS than their non-sarcoma enriched ccRCC counterparts. The presence of sarcoma expression signatures has not been previously evaluated in RCC. These signatures portend poor survival and may be clinically actionable, as they describe unique subtypes of RCC that may not correspond to histologic characterization.

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

scholarly journals Bioinformatic analysis identifies potentially key differentially expressed genes in oncogenesis and progression of clear cell renal cell carcinoma

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e8096 ◽  
Author(s):  
Haiping Zhang ◽  
Jian Zou ◽  
Ying Yin ◽  
Bo Zhang ◽  
Yaling Hu ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Differentially Expressed Genes ◽  
Renal Cell ◽  
Molecular Mechanisms ◽  
Clear Cell ◽  
Clinical Stage ◽  
Stage I ◽  
Differentially Expressed ◽  
Cell Renal Cell Carcinoma

Clear cell renal cell carcinoma (ccRCC) is one of the most common and lethal types of cancer within the urinary system. Great efforts have been made to elucidate the pathogeny. However, the molecular mechanism of ccRCC is still not well understood. The aim of this study is to identify key genes in the carcinogenesis and progression of ccRCC. The mRNA microarray dataset GSE53757 was downloaded from the Gene Expression Omnibus database. The GSE53757 dataset contains tumor and matched paracancerous specimens from 72 ccRCC patients with clinical stage I to IV. The linear model of microarray data (limma) package in R language was used to identify differentially expressed genes (DEGs). The protein–protein interaction (PPI) network of the DEGs was constructed using the search tool for the retrieval of interacting genes (STRING). Subsequently, we visualized molecular interaction networks by Cytoscape software and analyzed modules with MCODE. A total of 1,284, 1,416, 1,610 and 1,185 up-regulated genes, and 932, 1,236, 1,006 and 929 down-regulated genes were identified from clinical stage I to IV ccRCC patients, respectively. The overlapping DEGs among the four clinical stages contain 870 up-regulated and 645 down-regulated genes. The enrichment analysis of DEGs in the top module was carried out with DAVID. The results showed the DEGs of the top module were mainly enriched in microtubule-based movement, mitotic cytokinesis and mitotic chromosome condensation. Eleven up-regulated genes and one down-regulated gene were identified as hub genes. Survival analysis showed the high expression of CENPE, KIF20A, KIF4A, MELK, NCAPG, NDC80, NUF2, TOP2A, TPX2 and UBE2C, and low expression of ACADM gene could be involved in the carcinogenesis, invasion or recurrence of ccRCC. Literature retrieval results showed the hub gene NDC80, CENPE and ACADM might be novel targets for the diagnosis, clinical treatment and prognosis of ccRCC. In conclusion, the findings of present study may help us understand the molecular mechanisms underlying the carcinogenesis and progression of ccRCC, and provide potential diagnostic, therapeutic and prognostic biomarkers.

scholarly journals Patterns of gene expression characterize T1 and T3 clear cell renal cell carcinoma subtypes

PLoS ONE ◽  
2019 ◽  
Vol 14 (5) ◽  
pp. e0216793 ◽  
Author(s):  
Agnieszka M. Borys ◽  
Michał Seweryn ◽  
Tomasz Gołąbek ◽  
Łukasz Bełch ◽  
Agnieszka Klimkowska ◽  
...  
Keyword(s):  
Gene Expression ◽  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma

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.

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