Impact of cisplatin administration on protein expression levels in renal cell carcinoma: A proteomic analysis

Abstract Background Emerging evidence confirms that lncRNAs (long non-coding RNAs) are potential biomarkers that play vital roles in tumors. ZNF582-AS1 is a novel lncRNA that serves as a potential prognostic marker of cancers. However, the specific clinical significance and molecular mechanism of ZNF582-AS1 in ccRCC (clear cell renal cell carcinoma) are unclear. Methods Expression level and clinical significance of ZNF582-AS1 were determined by TCGA-KIRC data and qRT-PCR results of 62 ccRCCs. DNA methylation status of ZNF582-AS1 promoter was examined by MSP, MassARRAY methylation and demethylation analysis. Gain-of-function experiments were conducted to investigate the biological roles of ZNF582-AS1 in the phenotype of ccRCC. The subcellular localization of ZNF582-AS1 was detected by RNA FISH. iTRAQ, RNA pull-down and RIP-qRT-PCR were used to identify the downstream targets of ZNF582-AS1. rRNA MeRIP-seq and MeRIP-qRT-PCR were utilized to examine the N(6)-methyladenosine modification status. Western blot and immunohistochemistry assays were used to determine the protein expression level. Results ZNF582-AS1 was downregulated in ccRCC, and decreased ZNF582-AS1 expression was significantly correlated with advanced tumor stage, higher pathological stage, distant metastasis and poor prognosis. Decreased ZNF582-AS1 expression was caused by DNA methylation at the CpG islands within its promoter. ZNF582-AS1 overexpression inhibited cell proliferative, migratory and invasive ability, and increased cell apoptotic rate in vitro and in vivo. Mechanistically, we found that ZNF582-AS1 overexpression suppressed the N(6)-methyladenosine modification of MT-RNR1 by reducing rRNA adenine N(6)-methyltransferase A8K0B9 protein level, resulting in the decrease of MT-RNR1 expression, followed by the inhibition of MT-CO2 protein expression. Furthermore, MT-RNR1 overexpression reversed the decreased MT-CO2 expression and phenotype inhibition of ccRCC induced by increased ZNF582-AS1 expression. Conclusions This study demonstrates for the first time that ZNF582-AS1 functions as a tumor suppressor gene in ccRCC and ZNF582-AS1 may serve as a potential biomarker and therapeutic target of ccRCC.

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76P B7-H3 immune checkpoint protein expression is associated with immune exhaustion, overall survival and metastasis in clear cell renal cell carcinoma

Annals of Oncology ◽

10.1016/j.annonc.2021.08.2072 ◽

2021 ◽

Vol 32 ◽

pp. S1368

Author(s):

C.E. Nunes-Xavier ◽

M. Emaldi ◽

T. Øyjord ◽

G. Larrinaga ◽

P. Errarte ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Overall Survival ◽

Protein Expression ◽

Cell Carcinoma ◽

Immune Checkpoint ◽

Renal Cell ◽

Clear Cell ◽

Cell Renal Cell Carcinoma ◽

Checkpoint Protein ◽

Immune Exhaustion

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Identification of Proteins Differentially Expressed in the Conventional Renal Cell Carcinoma by Proteomic Analysis

Journal of Korean Medical Science ◽

10.3346/jkms.2005.20.3.450 ◽

2005 ◽

Vol 20 (3) ◽

pp. 450 ◽

Cited By ~ 32

Author(s):

Jeong Seok Hwa ◽

Hyo Jin Park ◽

Jae Hun Jung ◽

Sung Chul Kam ◽

Hyung Chul Park ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Proteomic Analysis ◽

Renal Cell ◽

Differentially Expressed ◽

Conventional Renal Cell Carcinoma

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

BMC Cancer ◽

10.1186/1471-2407-14-25 ◽

2014 ◽

Vol 14 (1) ◽

Cited By ~ 35

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

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SPOP Could Play a Potential Inhibitory Role in Human Renal Cell Carcinoma

10.21203/rs.3.rs-395336/v1 ◽

2021 ◽

Author(s):

zhi chen ◽

Zuan Li ◽

Deyong Nong ◽

Ximing Li ◽

Guihai Huang ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Cell Lines ◽

Renal Cell ◽

Immunohistochemical Staining ◽

Human Renal Cell Carcinoma ◽

Expression Levels ◽

Normal Tissues ◽

Proliferation And Apoptosis

Abstract Background: SPOP, a substrate adaptor of Cul3 ubiquitin ligase, plays crucial roles in solid neoplasms by promoting the ubiquitination and degradation of substrates. Limited studies have shown that SPOP is overexpressed in human renal cell carcinoma (RCC) tissue. However, the exact role of SPOP in RCC remains unclear and needs to be further elucidated. The present study showed that SPOP was expressed at different levels in different RCC cell lines. The purpose of this study was to explore the roles of SPOP in the biological features of RCC cells and determine the expression levels of SPOP in human tissue microarrays (TMAs) and kidney tissues.Methods: Here, SPOP was overexpressed by lentiviral vector transfection in ACHN and Caki-1 cells, and SPOP was knocked down in Caki-2 cells with similar transfection methods. The transfection efficiency was evaluated by quantitative PCR and western blotting analyses. The role of SPOP in the proliferation, migration, invasion and apoptosis of cell lines was determined by the MTT, wound-healing, Transwell and flow cytometry assays. Moreover, the cells were treated with different drug concentrations in proliferation and apoptosis assays to investigate the effect of sunitinib and IFN-α2b on the proliferation and apoptosis of SPOP-overexpressing cells and SPOP-knockdown RCC cells. Finally, immunohistochemical staining of SPOP was performed in kidney tissues and TMAs, which included RCC tissues and corresponding adjacent normal tissues.Results: Overexpression of SPOP inhibited cell proliferation, migration and invasion and increased cell apoptosis. Interestingly, sunitinib and IFN-α2b at several concentrations increased the proliferation inhibitory rate and total apoptosis rate of cells overexpressing SPOP. The findings of the present study showed that the SPOP protein was significantly expressed at low levels in most clear cell RCC (ccRCC) tissues and at relatively high levels in the majority of adjacent normal tissues and kidney tissues. Kaplan-Meier survival analysis showed that there was no statistically significant difference in cumulative survival based on the data of different SPOP expression levels in TMA and patients.Conclusions: In contrast to previous studies, our findings demonstrated that overexpression of SPOP might suppress the progression of RCC cells, which was supported by cell experiments and immunohistochemical staining. SPOP could be a potential tumour inhibitor in RCC.

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Tamm Horsfall protein expression by a small renal cell carcinoma presenting with metastases

Histopathology ◽

10.1111/j.1365-2559.1990.tb00767.x ◽

1990 ◽

Vol 17 (5) ◽

pp. 451-455 ◽

Cited By ~ 2

Author(s):

A. GAULIER ◽

G. LUCAS ◽

P. RONCO

Keyword(s):

Renal Cell Carcinoma ◽

Protein Expression ◽

Cell Carcinoma ◽

Renal Cell

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Prognostic significance and immune correlates of CD73 expression in renal cell carcinoma

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2020-001467 ◽

2020 ◽

Vol 8 (2) ◽

pp. e001467

Author(s):

Abhishek Tripathi ◽

Edwin Lin ◽

Wanling Xie ◽

Abdallah Flaifel ◽

John A Steinharter ◽

...

Keyword(s):

Gene Expression ◽

Renal Cell Carcinoma ◽

T Cell ◽

Protein Expression ◽

Cell Carcinoma ◽

Renal Cell ◽

Prognostic Significance ◽

Cox Regression Analysis ◽

Tcga Dataset ◽

Cd73 Expression

BackgroundCD73–adenosine signaling in the tumor microenvironment is immunosuppressive and may be associated with aggressive renal cell carcinoma (RCC). We investigated the prognostic significance of CD73 protein expression in RCC leveraging nephrectomy samples. We also performed a complementary analysis using The Cancer Genome Atlas (TCGA) dataset to evaluate the correlation of CD73 (ecto-5′-nucleotidase (NT5E), CD39 (ectonucleoside triphosphate diphosphohydrolase 1 (ENTPD1)) and A2 adenosine receptor (A2AR; ADORA2A) transcript levels with markers of angiogenesis and antitumor immune response.MethodsPatients with RCC with available archived nephrectomy samples were eligible for inclusion. Tumor CD73 protein expression was assessed by immunohistochemistry and quantified using a combined score (CS: % positive cells×intensity). Samples were categorized as CD73negative (CS=0), CD73low or CD73high (< and ≥median CS, respectively). Multivariable Cox regression analysis compared disease-free survival (DFS) and overall survival (OS) between CD73 expression groups. In the TCGA dataset, samples were categorized as low, intermediate and high NT5E, ENTPD1 and ADORA2A gene expression groups. Gene expression signatures for infiltrating immune cells, angiogenesis, myeloid inflammation, and effector T-cell response were compared between NT5E, ENTPD1 and ADORA2A expression groups.ResultsAmong the 138 patients eligible for inclusion, ‘any’ CD73 expression was observed in 30% of primary tumor samples. High CD73 expression was more frequent in patients with M1 RCC (29% vs 12% M0), grade 4 tumors (27% vs 13% grade 3 vs 15% grades 1 and 2), advanced T-stage (≥T3: 22% vs T2: 19% vs T1: 12%) and tumors with sarcomatoid histology (50% vs 12%). In the M0 cohort (n=107), patients with CD73high tumor expression had significantly worse 5-year DFS (42%) and 10-year OS (22%) compared with those in the CD73negative group (DFS: 75%, adjusted HR: 2.7, 95% CI 1.3 to 5.9, p=0.01; OS: 64%, adjusted HR: 2.6, 95% CI 1.2 to 5.8, p=0.02) independent of tumor stage and grade. In the TCGA analysis, high NT5E expression was associated with significantly worse 5-year OS (p=0.008). NT5E and ENTPD1 expression correlated with higher regulatory T cell (Treg) signature, while ADORA2A expression was associated with increased Treg and angiogenesis signatures.ConclusionsHigh CD73 expression portends significantly worse survival outcomes independent of stage and grade. Our findings provide compelling support for targeting the immunosuppressive and proangiogenic CD73–adenosine pathway in RCC.

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

Journal of International Medical Research ◽

10.1177/0300060520936041 ◽

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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