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.

Decreased prolyl hydroxylase 3 mRNA expression in oncocytomas compared with clear cell renal cell carcinoma

2020 ◽  
Vol 35 (4) ◽  
pp. 80-86
Author(s):  
Spyridon Kampantais ◽  
Ilias Kounatidis ◽  
Vasiliki Kotoula ◽  
Ioannis Vakalopoulos ◽  
Konstantinos Gkagkalidis ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Mrna Expression ◽  
Renal Cell ◽  
Clear Cell ◽  
Prolyl Hydroxylase ◽  
Renal Tumors ◽  
Cell Renal Cell Carcinoma ◽  
Expression Levels ◽  
Fresh Frozen

Introduction: Hypoxia inducible factors (HIF) and prolyl hydroxylase domain (PHD) enzymes play a central role in tumor progression in clear cell renal cell carcinoma (ccRCC). However, there are currently no data regarding the behavior of this pathway (HIF/PHD) in a large number of benign renal tumors, the oncocytomas. The aim of the present study was to compare the expression levels of these factors between ccRCC and oncocytoma tumors. Material and methods: A total of 56 fresh frozen specimens from patients with ccRCC and 14 oncocytoma specimens were analyzed via reverse transcription-quantitative polymerase chain reaction in order to assess the expression levels of HIF-1α, HIF-2α, PHD1, PHD2, and PHD3. The analysis involved both fresh frozen tumor samples as well as adjacent normal kidney tissues. Results: In ccRCC, HIF-1α and HIF-2α levels were upregulated in 65.5% and 71.4% of cases, respectively. PHD3 was downregulated only in 15.4% of the ccRCC cases, in contrast with oncocytoma cases, which exhibited low expression levels in the majority. The upregulation of PHD3 messenger RNA (mRNA) levels in ccRCC when compared with oncocytoma was statistically significant ( P<0.001). No other comparisons (HIF-1α, HIF-2α, PHD1, and PHD2) were significantly different. HIF-2α and PHD3 mRNA expression levels were negatively correlated with Fuhrman Grade ( P=0.029 and P=0.026, respectively) in ccRCC. Conclusion: To the best of our knowledge, this is the first time that the HIF/PHD pathway was compared between ccRCC and a common benign tumor, identifying the upregulation of PHD3 as the possible underlying factor guiding the difference in the behavior of ccRCC.

scholarly journals Up Regulation of GSDMB Is Correlated With Poor Prognosis and Immune Infiltrates in Clear Cell Renal Cell Carcinoma

2021 ◽  
Author(s):  
Yuanshan Cui ◽  
Zhongbao Zhou ◽  
Yumeng Chai ◽  
Yong Zhang
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Mrna Expression ◽  
Roc Curve ◽  
Renal Cell ◽  
Poor Prognosis ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma ◽  
Normal Tissues ◽  
Kaplan Meier

Abstract Background: Gasdermin B (GSDMB) is part of the gasdermin (GSDM) family and they use varying means of domain interactions in molecules to adjust their pore-forming and lipid-binding actions. The GSDM family has roles in the regulation of cell differentiation and proliferation, particularly in the process of pyroptosis. Nonetheless, the correlation of GSDMB with immune infiltrates and its prognostic values in Clear Cell Renal Cell Carcinoma (ccRCC) are still undefined. Therefore, we assessed the correlation of GSDMB with immune infiltrates and its prognostic role in ccRCC. Methods: The transcriptional expression profiles of GSDMB in ccRCC tissues in addition to normal tissues were retrieved from the Cancer Genome Atlas (TCGA), and additionally verified in a different independent cohort, which was obtained from the gene expression omnibus (GEO) database. The Human Protein Atlas and the Clinical Proteomic Tumor Analysis Consortium (CPTAC) were accessed to assess the protein expression of GSDMB. To differentiate between ccRCC and surrounding normal tissues, the receiver operating characteristic (ROC) curve was applied. Relationships between GSDMB expression, clinicopathologicical variables, and overall survival (OS) were evaluated with multivariate methods as well as Kaplan-Meier survival curves. Protein-protein interaction (PPI) networks were created with String. Functional enrichment analyses were conducted by utilizing the “ClusterProfiler” package. The tumor immune estimation resource (TIMER) and tumor-immune system interaction database (TISIDB) were utilized to determine the association between the mRNA expression of GSDMB and immune infiltrates. Results: GSDMB expression was significantly more up regulated in ccRCC tissues compared to surrounding normal tissues. An increase in the mRNA expression of GSDMB was related to high pathologic stage and advanced TNM stage. The analysis of the ROC curve indicated that GSDMB had an AUC value of 0.820 to distinguish between ccRCC tissues and adjacent normal controls. Kaplan-Meier survival analysis indicated that ccRCC patients with high-GSDMB had a poorer prognosis compared to those with low-GSDMB (P < 0.001). Correlation analysis showed that the mRNA expression of GSDMB was associated with immune infiltrates and the purity of the tumor. Upregulation of GSDMB is significantly related to immune infiltrates and poor survival in ccRCC. Conclusions: The results of this study indicates that GSDMB could be regarded as a biomarker for the detection of poor prognosis and potential target of immune treatment in ccRCC.

scholarly journals Upregulated GSDMB in Clear Cell Renal Cell Carcinoma Is Associated with Immune Infiltrates and Poor Prognosis

2021 ◽  
Vol 2021 ◽  
pp. 1-22
Author(s):  
Yuanshan Cui ◽  
Zhongbao Zhou ◽  
Yumeng Chai ◽  
Yong Zhang
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Mrna Expression ◽  
Roc Curve ◽  
Renal Cell ◽  
Poor Prognosis ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma ◽  
Normal Tissues ◽  
Kaplan Meier

Gasdermin B (GSDMB) is part of the gasdermin (GSDM) family, and they use varying means of domain interactions in molecules to adjust their pore-forming and lipid-binding actions. The GSDM family has roles in the regulation of cell differentiation and proliferation, particularly in the process of pyroptosis. Nonetheless, the correlation of GSDMB with immune infiltrates and its prognostic values in clear cell renal cell carcinoma (ccRCC) are still undefined. Therefore, we assessed the correlation of GSDMB with immune infiltrates and its prognostic role in ccRCC. The transcriptional expression profiles of GSDMB in ccRCC tissues in addition to normal tissues were retrieved from The Cancer Genome Atlas (TCGA) and additionally verified in a different independent cohort, which was obtained from the Gene Expression Omnibus (GEO) database. The Human Protein Atlas and the Clinical Proteomic Tumor Analysis Consortium (CPTAC) were used to assess the protein expression of GSDMB. To assess the effectiveness of GSDMB in distinguishing ccRCC from normal samples, the receiver operating characteristic (ROC) curve analysis was performed. Relationships between GSDMB expression, clinicopathological variables, and overall survival (OS) were evaluated with multivariate methods as well as Kaplan-Meier survival curves. Protein-protein interaction (PPI) networks were created with STRING. Functional enrichment analyses were conducted by utilizing the “ClusterProfiler” package. The Tumor Immune Estimation Resource (TIMER) and tumor-immune system interaction database (TISIDB) were utilized to determine the association between the mRNA expression of GSDMB and immune infiltrates. GSDMB expression was significantly more upregulated in ccRCC tissues compared to surrounding normal tissues. An increase in the mRNA expression of GSDMB was related to the high pathologic stage and advanced TNM stage. The analysis of the ROC curve indicated that GSDMB had an AUC value of 0.820 to distinguish between ccRCC tissues and adjacent normal controls. Kaplan-Meier survival analysis indicated that ccRCC patients with high GSDMB had a poorer prognosis compared to those with low GSDMB ( P < 0.001 ). Correlation analysis showed that the mRNA expression of GSDMB was associated with immune infiltrates and the purity of the tumor. Upregulation of GSDMB is significantly related to immune infiltrates and poor survival in ccRCC. The results of this study indicate that GSDMB could be regarded as a biomarker for the detection of poor prognosis and potential target of immune treatment in ccRCC.

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 COL6A2/3 can serve as potential therapeutic targets and prognostic biomarkers for clear cell renal cell carcinoma

2020 ◽  
Author(s):  
Wingkeung Yiu ◽  
Can-Xuan Li ◽  
Jie Chen
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Mrna Expression ◽  
Renal Cell ◽  
Clear Cell ◽  
Therapeutic Targets ◽  
Gene Set Enrichment Analysis ◽  
Prognostic Biomarkers ◽  
Cell Renal Cell Carcinoma ◽  
Tumorigenesis And Progression

Abstract Background: Growing evidence has shown that the type VI collagen alpha chain (COL6A) family involved in the tumorigenesis and progression of diverse malignancies; however, its biological roles and potential mechanisms in clear cell renal cell carcinoma (ccRCC) remain unknown. The study was designed to explore the potential mechanisms and functions of COL6As in ccRCC.Methods: ONCOMINE and GEPIA databases were used to compare the transcriptional expression data of COL6As in ccRCC samples and normal renal samples. UALCAN database was utilized to determine the association between clinicopathological features and COL6As expression. Kaplan–Meier method was employed to determine the prognostic value of COL6As mRNA expression in ccRCC. CBioPortal database was used to investigate the genetic alterations of COL6As in ccRCC. Co-expression analyses, functional enrichment analyses, and gene set enrichment analysis (GSEA) were utilized to explore the potential action mechanisms of COL6As in ccRCC. Finally, we estimated the relationship between COL6As expression with immune cell infiltrates.Results: Upregulated transcriptional COL6A2/COL6A3 expression was observed in ccRCC specimens by comparison with noncancerous renal specimens. Patients with increased COL6A2/COL6A3 mRNA expression have a poor clinical outcome and unfavorable prognosis. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and GSEA analyses showed that COL6A2/COL6A3 might promote the tumorigenesis and progression of ccRCC by involving in several cancer-related pathways, such as axon guidance, focal adhesion, ECM receptor interaction. Besides, we found that COL6A2/COL6A3 expression was significantly associated with immune infiltration levels in ccRCC.Conclusions: COL6A2 and COL6A3 could act as candidate prognostic biomarkers and therapeutic targets in ccRCC. However, further experimental work was required to validate the conclusions.

scholarly journals Expression levels of immune control points genes in renal cell carcinoma

2020 ◽  
pp. 64-65
Author(s):  
Н.В. Апанович ◽  
А.А. Алимов ◽  
П.В. Апанович ◽  
А.Ю. Кузеванова ◽  
Д.Ж. Мансорунов ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
New Drugs ◽  
Control Points ◽  
Immune Control ◽  
Cell Renal Cell Carcinoma ◽  
Expression Levels ◽  
Further Development

Внедрение в терапию рака новых препаратов на основе ингибирования иммунных контрольных точек (ИКТ) существенно улучшило прогноз для больных. Тем не менее, такая терапия не всегда эффективна. Для вскрытия возможных причин этого мы изучили уровни экспрессии PD-L1 и других генов ИКТ - IDO1, CEACAM1, PVR, TDO2, CD276, GAL9 и ADAM17 в образцах светлоклеточного почечно-клеточного рака. В результате анализа выявили наиболее часто экспрессирующиеся совместно с PD-L1 гены - IDO1, TDO2, CD276, GAL9 и ADAM17. Значимую корреляцию с экспрессией PD-L1 имела экспрессия генов ADAM17, PVR и CD276. Полученные данные могут иметь значение для дальнейшего развития терапии на основе блокирования ИКТ, включая PD-L1. The introduction of new drugs based on the inhibition of immune control points (ICР) into cancer therapy has significantly improved the prognosis for patients. However, such therapy is not always effective. To reveal the possible reasons for this, we studied the expression levels of PD-L1 and other ICР genes - IDO1, CEACAM1, PVR, TDO2, CD276, GAL9 and ADAM17 in samples of clear cell renal cell carcinoma. The analysis revealed the genes most often expressed together with PD-L1 - IDO1, TDO2, CD276, GAL9 and ADAM17. Significant correlation with the expression of PD-L1 was found for the expression of ADAM17, PVR, and CD276 genes. The data obtained may be important for the further development of therapy based on blocking ICP, including PD-L1.

scholarly journals Long Non-Coding RNA LUCAT1 Promotes Proliferation and Invasion in Clear Cell Renal Cell Carcinoma Through AKT/GSK-3β Signaling Pathway

2018 ◽  
Vol 48 (3) ◽  
pp. 891-904 ◽  
Author(s):  
Zaosong Zheng ◽  
Fengjin Zhao ◽  
Dingjun Zhu ◽  
Jinli Han ◽  
Haicheng Chen ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Migration And Invasion ◽  
Cell Renal Cell Carcinoma ◽  
Normal Tissues ◽  
Gsk 3Β ◽  
Proliferation And Invasion

Background/Aims: Long non-coding RNAs (lncRNAs) have emerged as new regulators and biomarkers in several cancers. However, few lncRNAs have been well characterized in clear cell renal cell carcinoma (ccRCC). Methods: We investigated the lncRNA expression profile by microarray analysis in 5 corresponding ccRCC tissues and adjacent normal tissues. Lung cancer–associated transcript 1 (LUCAT1) expression was examined in 90 paired ccRCC tissues by real-time PCR and validated by The Cancer Genome Atlas (TCGA) database. Kaplan-Meier analysis was used to examine the prognostic value of LUCAT1 and CXCL2 in ccRCC patients. Loss and gain of function were performed to explore the effect of LUCAT1 on proliferation and invasion in ccRCC cells. Western blotting was performed to evaluate the underlying mechanisms of LUCAT1 in ccRCC progression. Chemokine stimulation assay was performed to investigate possible mechanisms controlling LUCAT1 expression in ccRCC cells. Enzyme-linked immunosorbent assays were performed to determine serum CXCL2 in ccRCC patients and healthy volunteers. Receiver operating characteristic curve analysis was performed to examine the clinical diagnostic value of serum CXCL2 in ccRCC. Results: We found that LUCAT1 was significantly upregulated in both clinical ccRCC tissues (n = 90) and TCGA ccRCC tissues (n = 448) compared with normal tissues. Statistical analysis revealed that the LUCAT1 expression level positively correlated with tumor T stage (P < 0.01), M stage (P < 0.01), and TNM stage (P < 0.01). Overall survival and disease-free survival time were significantly shorter in the high-LUCAT1-expression group than in the low-LUCAT1-expression group (log-rank P < 0.01). LUCAT1 knockdown inhibited ccRCC cell proliferation and colony formation, induced cell cycle arrest at G1 phase, and inhibited cell migration and invasion. Overexpression of LUCAT1 promoted proliferation, migration, and invasion of ccRCC cells. Mechanistic investigations showed that LUCAT1 induced cell cycle G1 arrest by regulating the expression of cyclin D1, cyclin-dependent kinase 4, and phosphorylated retinoblastoma transcriptional corepressor 1. Moreover, LUCAT1 promoted proliferation and invasion in ccRCC cells partly through inducing the phosphorylation of AKT and suppressing the phosphorylation of GSK-3β. We also revealed that chemokine CXCL2, upregulated in ccRCC, induced LUCAT1 expression and might be a diagnostic and prognostic biomarker in ccRCC. Conclusions: LUCAT1 was upregulated in ccRCC tissues and renal cancer cell lines, and significantly correlated with malignant stage and poor prognosis in ccRCC. LUCAT1 promoted proliferation and invasion in ccRCC cells through the AKT/GSK-3β signaling pathway. We also revealed that LUCAT1 overexpression was induced by chemokine CXCL2. These findings indicate that the CXCL2/LUCAT1/AKT/GSK-3β axis is a potential therapeutic target and molecular biomarker for ccRCC.

Sign in / Sign up

Export Citation Format

Share Document