Renal carcinoma related factor is up-regulated in high Fuhrman grade renal cell carcinoma tissues and affects prognosis of patients

BACKGROUND: Long non-coding RNAs (lncRNAs) play important roles in cancer development, yet their roles in renal carcinoma remain unclear. OBJECTIVE: We performed this study in order to investigate the expression and roles of lncRNAs in renal cell carcinoma. METHODS: In this study, we investigated the expression of lncRNAs in renal cell carcinoma through microarray analysis. Quantitative real-time PCR was performed to measure the expression of lncRNAs. Gain- or loss-of-function experiments were performed to investigate the roles of lncRNAs in cell proliferation and apoptosis. RNA pull-down and western blotting were performed to explore the underlying mechanism. RESULTS: The microarray analysis identified an upregulated lncRNA MIR4435-1HG in renal carcinoma. The expression level of MIR4435-1HG was correlated with TNM stage, tumor size, and Fuhrman grade. High expression of MIR4435-1HG indicated poor prognosis. MIR4435-1HG knockdown inhibited cell proliferation, and suppressed the migrating and invasive capacity of renal carcinoma cells. RNA pull-down followed by mass spectrometry revealed an interaction between MIR4435-1HG and pyruvate carboxylase, which was later corroborated by western blotting. CONCLUSIONS: MIR4435-1HG plays a critical role in the oncogenesis of renal cell carcinoma and may serve as a potential biomarker for renal cell carcinoma.

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Nuclear and cytosolic pS727-STAT3 levels correlate with overall survival of patients affected by clear cell renal cell carcinoma (ccRCC)

Scientific Reports ◽

10.1038/s41598-021-86218-x ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Jazmine Arévalo ◽

David Lorente ◽

Enrique Trilla ◽

María Teresa Salcedo ◽

Juan Morote ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Overall Survival ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Cell Renal Cell Carcinoma ◽

Independent Manner ◽

Fuhrman Grade ◽

Transcription 3 ◽

Aggressive Subtype

AbstractClear cell renal cell carcinoma (ccRCC) is the most frequent and aggressive subtype of renal carcinoma. So far, the basis of its oncogenesis remains unclear resulting in a deficiency of usable and reliable biomarkers for its clinical management. Previously, we showed that nuclear expression of the signal transducer and activator of transcription 3 (STAT3), phosphorylated at its serine 727 (pS727), was inversely proportional to the overall survival of ccRCC patients. Therefore, in the present study, we validated the value of pS727-STAT3 as a clinically relevant biomarker in ccRCC. This work is a retrospective study on 82 ccRCC patients treated with nephrectomy and followed-up for 10 years. Immunohistochemical expression of pS727-STAT3 was analyzed on a tissue microarray and nuclear and cytosolic levels were correlated with clinical outcome of patients. Our results showed that pS727-STAT3 levels, whether in the nucleus (p = 0.002; 95% CI 1.004–1.026) or the cytosol (p = 0.040; 95% CI 1.003–1.042), significantly correlate with patients’ survival in an independent-manner of clinicopathological features (Fuhrman grade, risk group, and tumor size). Moreover, we report that patients with high pS727-STAT3 levels who undergone adjuvant therapy exhibited a significant stabilization of the disease (~ 20 months), indicating that pS727-STAT3 can pinpoint a subset of patients susceptible to respond well to treatment. In summary, we demonstrated that high pS727-STAT3 levels (regardless of their cellular location) correlate with low overall survival of ccRCC patients, and we suggested the use of pS727-STAT3 as a prognostic biomarker to select patients for adjuvant treatment to increase their survival.

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Development and characterization of a novel mAb against bilitranslocase - a new biomarker of renal carcinoma

Radiology and Oncology ◽

10.2478/raon-2013-0026 ◽

2013 ◽

Vol 47 (2) ◽

pp. 128-137 ◽

Cited By ~ 8

Author(s):

Sendi Montanic ◽

Michela Terdoslavich ◽

Uros Rajcevic ◽

Luigina De Leo ◽

Serena Department of Medical Sciences, Uni ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Monoclonal Antibodies ◽

Cell Carcinoma ◽

Renal Cell ◽

Renal Carcinoma ◽

Vascular Endothelial Cells ◽

Polyclonal Antibodies ◽

Functional Characterization ◽

Immunological Approach

Background. Bilitranslocase (TC 2.A.65.1.1) is a bilirubin-specific membrane transporter, found on absorptive (stomach and intestine) and excretory (kidney and liver) epithelia and in vascular endothelium. Polyclonal antibodies have been raised in rabbits in the past, using a synthetic peptide corresponding to AA65-77 of rat liver bilitranslocase, as an antigen. Affinity-purified antibodies from immune sera have been found to inhibit various membrane transport functions, including the bilirubin uptake into human hepatocytes and the uptake of some flavonoids into human vascular endothelial cells. It was described by means of immunohistochemistry using polyclonal antibodies that bilitranslocase expression is severely down-regulated in clear cell renal carcinoma. The aim of our work was development and characterization of high-affinity, specific mAbs against bilitranslocase, which can be used as a potential diagnostic tool in renal cell carcinoma as well as in a wide variety of biological assays on different human tissues. Materials and methods. Mice were immunized with a multi-antigen peptide corresponding to segment 65-75 of predicted primary structure of the bilitranslocase protein. By a sequence of cloning, immune- and functional tests, we aimed at obtaining a specific monoclonal antibody which recognizes a 37 kDa membrane protein, and influences the transport activity of bilitranslocase. Results. On the basis of previous results, specific IgM monoclonal antibodies were produced in BALB/c mice, in order to further improve and extend the immunological approach to the study of bilitranslocase in renal cancer cells as well as to develop its potential diagnostics use. Conclusions. In this article we show an immunological approach, based on newly developed monoclonal antibodies, to a detailed biochemical and functional characterization of a protein whose gene and protein structure is still unknown. We were able to demonstrate our novel mAb as a tumor marker candidate of renal cell carcinoma, which may prove useful in the diagnostic procedures.

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Obstructive sleep apnea and Fuhrman grade in patients with clear cell renal cell carcinoma treated surgically

World Journal of Urology ◽

10.1007/s00345-016-1830-6 ◽

2016 ◽

Vol 35 (1) ◽

pp. 51-56 ◽

Cited By ~ 7

Author(s):

Antoni Vilaseca ◽

Daniel P. Nguyen ◽

Emily A. Vertosick ◽

Renato B. Corradi ◽

Mireia Musquera ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Obstructive Sleep Apnea ◽

Sleep Apnea ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Cell Renal Cell Carcinoma ◽

Fuhrman Grade ◽

Obstructive Sleep

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Solitary Liver Metastasis of Renal Cell Carcinoma 8 Years After Nephrectomy

10.21203/rs.3.rs-506315/v1 ◽

2021 ◽

Author(s):

Haoran Lu ◽

Shouye Zhao ◽

Guodong Ma ◽

Rou Zhao ◽

Bin Zhang

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Radical Nephrectomy ◽

Renal Carcinoma ◽

Pet Ct ◽

Solitary Liver ◽

Solitary Metastases

Abstract Background: Renal cell carcinoma (RCC) is the most common renal malignancy in adults. RCC can metastasize to various organs of the human body, including lung, bone, brain, liver, and adrenal gland. However, solitary metastases are relatively rare in clinical practice, and surgical treatment is still the preferred treatment.Case report: We present a 68-year-old male patient who was performed laparoscopic radical left nephrectomy for RCC 8 years ago. Postoperative routine examination revealed an occupying lesion in the liver. Further PET-CT suggested hepatic metastasis of RCC thus undergoing laparoscopic left hepatectomy. Pathology confirmed metastatic RCC in the liver. The patient recovered well after the operation, and there was no sign of recurrence during the follow-up for six months after the operation.Conclusion: Patients with renal carcinoma can still have recurrence and metastasis after radical nephrectomy for many years. Therefore, long-term close follow-up is beneficial to patients with radical nephrectomy.

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Analysis of plasma KIM-1 as a biomarker for recurrence risk after resection for localized renal cell carcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.6_suppl.342 ◽

2021 ◽

Vol 39 (6_suppl) ◽

pp. 342-342

Author(s):

Wenxin Xu ◽

Maneka Puligandla ◽

Brian Halbert ◽

Naomi B. Haas ◽

Keith Flaherty ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Failure Time ◽

Residual Disease ◽

Disease Free Survival ◽

Accelerated Failure Time Model ◽

Prognostic Models ◽

Plasma Samples ◽

Fuhrman Grade

342 Background: Recurrence is common after nephrectomy for renal cell carcinoma (RCC), but no circulating biomarkers are available to identify patients at highest risk of recurrence who may benefit from adjuvant therapy. Kidney injury molecule-1 (KIM-1) is overexpressed in RCC and its ectodomain circulates in plasma. We investigated whether plasma KIM-1 is a prognostic biomarker in patients with localized RCC after nephrectomy. Methods: Banked plasma samples were analyzed from the ECOG-ACRIN 2805 (ASSURE) trial evaluating adjuvant sunitinib, sorafenib, and placebo in resected high-risk RCC. KIM-1 levels were measured at trial enrollment 4-12 weeks post-nephrectomy (baseline) and on cycle 2 day 1 (C2D1) using a previously validated microbead assay. A lognormal accelerated failure time model was used to test for association between circulating KIM-1 and disease-free survival (DFS). Results: Plasma samples from 418 patients were analyzed. In univariable and multivariable analyses, higher post-nephrectomy KIM-1 was associated with worse DFS across all study arms. This association remained independently significant after adjustment for Fuhrman grade, T-stage, N-stage, and tumor histology (survival time ratio 0.56 for 75th vs 25th percentile of KIM-1, 95% CI 0.42-0.73, p < 0.001). The association between KIM-1 and DFS was stronger among patients with pathologic nodal involvement. The addition of baseline KIM-1 improved the concordance of both the SSIGN and UISS prognostic models (SSIGN concordance 0.57 vs 0.43, p = 0.05; UISS concordance 0.60 vs 0.40, p = 0.0005). C2D1 KIM-1 was not an independent predictor for DFS after adjusting for baseline KIM-1. Conclusions: Elevated plasma KIM-1 level at post-nephrectomy baseline is associated with worse DFS in RCC. This is consistent with the hypothesis that post-nephrectomy plasma KIM-1 may be a biomarker for microscopic residual disease. The model was additionally adjusted for papillary and chromophobe histology, sex, and ECOG performance status. [Table: see text]

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CT texture analysis in the differentiation of major renal cell carcinoma subtypes and correlation with Fuhrman grade

European Radiology ◽

10.1007/s00330-019-06260-2 ◽

2019 ◽

Vol 29 (12) ◽

pp. 6922-6929 ◽

Cited By ~ 17

Author(s):

Yu Deng ◽

Erik Soule ◽

Aster Samuel ◽

Sakhi Shah ◽

Enming Cui ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Texture Analysis ◽

Renal Cell ◽

Fuhrman Grade ◽

Ct Texture Analysis

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Treatment of metastatic renal cell carcinoma with coumarin (1,2-benzopyrone) and cimetidine: a pilot study.

Journal of Clinical Oncology ◽

10.1200/jco.1987.5.6.862 ◽

1987 ◽

Vol 5 (6) ◽

pp. 862-866 ◽

Cited By ~ 81

Author(s):

M E Marshall ◽

L Mendelsohn ◽

K Butler ◽

L Riley ◽

J Cantrell ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Pilot Study ◽

Cell Carcinoma ◽

Metastatic Renal Cell Carcinoma ◽

Renal Cell ◽

Renal Carcinoma ◽

Optimal Dose ◽

Measurable Disease ◽

Duration Of Response ◽

Progression Of Disease

Forty-five patients with metastatic renal cell carcinoma were treated with coumarin (1,2-benzopyrone) and cimetidine. Patients received coumarin, 100 mg orally daily; cimetidine administration, 300 mg orally four times daily, was initiated on day 15 of therapy, and treatment with both drugs was continued until progression of disease. Three patients are too early to evaluate (on study less than or equal to 2 months with no change in tumor status). Objective responses (greater than or equal to 50% reduction in measurable disease) occurred in 14 of 42 evaluable patients (33.3%) (the 95% confidence interval based on this rate is +/- 14.3%), with three complete responses and 11 partial responses (PR). Complete responses lasted 9.5, 4+, and 9.5+ months. The median duration of response for the PR group was 5 months (range, 4 to 21+ months). Twelve patients experienced stabilization of disease ranging from 4 to 16.5+ months. No response was seen in 16 patients. There was no symptomatic, hematologic, or chemical (organ dysfunction) toxicity among the 45 patients treated. Coumarin and cimetidine appear to be safe and active agents in the treatment of metastatic renal carcinoma. Further studies are required to determine the optimal dose and scheduling of these agents.

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Treatment of Metastatic Renal Cell Carcinoma With a Combination of Bevacizumab and Erlotinib

Journal of Clinical Oncology ◽

10.1200/jco.2005.01.8234 ◽

2005 ◽

Vol 23 (31) ◽

pp. 7889-7896 ◽

Cited By ~ 223

Author(s):

John D. Hainsworth ◽

Jeffrey A. Sosman ◽

David R. Spigel ◽

Donna L. Edwards ◽

Cara Baughman ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Growth Factor ◽

Cell Carcinoma ◽

Skin Rash ◽

Renal Cell ◽

Renal Carcinoma ◽

Clear Cell ◽

Targeted Agents ◽

Clear Cell Renal Carcinoma ◽

Cell Renal Carcinoma

Purpose To evaluate the efficacy and toxicity of combined treatment with two targeted agents, an antibody against vascular endothelial growth factor (bevacizumab) and an epidermal growth factor receptor tyrosine kinase inhibitor (erlotinib), in the treatment of patients with metastatic clear-cell renal carcinoma. Patients and Methods Sixty-three patients with metastatic clear-cell renal carcinoma were treated with bevacizumab 10 mg/kg intravenously every 2 weeks and erlotinib 150 mg orally daily. Patients were reevaluated after 8 weeks of treatment; patients who responded continued treatment until they experienced tumor progression. Results Fifteen (25%) of 59 assessable patients (95% CI, 16% to 37%) had objective responses to treatment, and an additional 36 patients (61%) had stable disease after 8 weeks of treatment. Only eight patients' (14%) disease had progressed at this time point. The median and 1-year progression-free survivals were 11 months and 43%, respectively. After a median follow-up of 15 months, median survival has not been reached; survival at 18 months was 60%. Treatment was generally well tolerated; only two patients discontinued treatment because of toxicity (skin rash). Grade 1/2 skin rash and diarrhea were the most frequent treatment-related toxicities. Conclusion The combination of bevacizumab and erlotinib is an effective and well-tolerated treatment for patients with advanced renal cell carcinoma. The efficacy of these two drugs in combination suggests that targeting of separate pathways critical to tumor growth and dissemination may achieve results superior to either drug as a single agent. Additional development of this and other combinations of targeted agents is warranted.

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