RESUMO
BACKGROUND: Over 90% of cancer-related deaths in clear cell renal cell carcinoma (RCC) are caused by tumor relapse and metastasis. Thus, there is an urgent need for new molecular markers that can potentiate the efficacy of the current clinical-based models of prognosis assessment. The objective of this study is to evaluate the potential significance of lactate dehydrogenase A (LDHA), assessed by immunohistochemical staining, as a prognostic marker in clear cell renal cell carcinoma in relation to clinicopathological features and clinical outcome. METHODS: We assessed the expression of LDHA at the protein level, by immunohistochemistry, and correlated its expression with multiple clinicopathological features including tumor size, clinical stage, histological grade, disease-free and overall survival in 385 patients with primary clear cell renal cell carcinoma. We also correlated the LDHA expression with overall survival, at mRNA level, in an independent data set of 170 clear cell renal cell carcinoma cases from The Cancer Genome Atlas databases. Cox proportional hazards models adjusted for the potential clinicopathological factors were used to test for associations between the LDHA expression and both disease-free survival and overall survival. RESULTS: There is statistically significant positive correlation between LDHA level of expression and tumor size, clinical stage and histological grade. Moreover, LDHA expression shows significantly inverse correlation with both disease-free survival and overall survival in patients with clear cell renal cell carcinoma. Our results are validated by examining LDHA expression, at the mRNA level, in the independent data set of clear cell renal cell carcinoma cases from The Cancer Genome Atlas databases which also shows that higher lactate dehydrogenase A expression is associated with significantly shorter overall survival. CONCLUSION: Our results indicate that LDHA up-regulation can be a predictor of poor prognosis in clear cell renal cell carcinoma. Thus, it represents a potential prognostic biomarker that can boost the accuracy of other prognostic models in patients with clear cell renal cell carcinoma.
Assuntos
Biomarcadores Tumorais/genética , Carcinoma de Células Renais/diagnóstico , Regulação Neoplásica da Expressão Gênica , Neoplasias Renais/diagnóstico , L-Lactato Desidrogenase/genética , RNA Mensageiro/genética , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Feminino , Humanos , Isoenzimas/genética , Isoenzimas/metabolismo , Neoplasias Renais/genética , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , L-Lactato Desidrogenase/metabolismo , Lactato Desidrogenase 5 , Masculino , Gradação de Tumores , Estadiamento de Neoplasias , Medicina de Precisão , Prognóstico , RNA Mensageiro/metabolismo , Análise de Sobrevida , Carga TumoralRESUMO
There are no serum biomarkers for the accurate diagnosis of clear cell renal cell carcinoma (ccRCC). Diagnosis and decision of nephrectomy rely on imaging which is not always accurate. Non-invasive diagnostic biomarkers are urgently required. In this study, we preformed quantitative proteomics analysis on a total of 199 patients including 30 matched pairs of normal kidney and ccRCC using isobaric tags for relative and absolute quantitation (iTRAQ) labeling and LC-MS/MS analysis to identify differentially expressed proteins. We found 55 proteins significantly dysregulated in ccRCC compared to normal kidney tissue. 54 were previously reported to play a role in carcinogenesis, and 39 are secreted proteins. Dysregulation of alpha-enolase (ENO1), L-lactate dehydrogenase A chain (LDHA), heat shock protein beta-1 (HSPB1/Hsp27), and 10 kDa heat shock protein, mitochondrial (HSPE1) was confirmed in two independent sets of patients by western blot and immunohistochemistry. Pathway analysis, validated by PCR, showed glucose metabolism is altered in ccRCC compared to normal kidney tissue. In addition, we examined the utility of Hsp27 as biomarker in serum and urine. In ccRCC patients, Hsp27 was elevated in the urine and serum and high serum Hsp27 was associated with high grade (Grade 3-4) tumors. These data together identify potential diagnostic biomarkers for ccRCC and shed new light on the molecular mechanisms that are dysregulated and contribute to the pathogenesis of ccRCC. Hsp27 is a promising diagnostic marker for ccRCC although further large-scale studies are required. Also, molecular profiling may help pave the road to the discovery of new therapies.
Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma de Células Renais/metabolismo , Neoplasias Renais/metabolismo , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/urina , Carcinoma de Células Renais/sangue , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/urina , Estudos de Casos e Controles , Feminino , Perfilação da Expressão Gênica , Proteínas de Choque Térmico HSP27/sangue , Proteínas de Choque Térmico HSP27/genética , Proteínas de Choque Térmico HSP27/urina , Proteínas de Choque Térmico , Humanos , Imuno-Histoquímica , Neoplasias Renais/sangue , Neoplasias Renais/genética , Neoplasias Renais/urina , Masculino , Chaperonas Moleculares , Proteínas de Neoplasias/sangue , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Proteínas de Neoplasias/urina , Prognóstico , Proteômica/métodosRESUMO
Bilateral nephrectomy for transitional cell carcinoma of the renal pelvis is a rare procedure. We report two cases of bilateral nephrectomy for transitional cell carcinoma. Both patients were placed on dialysis. A review of the literature revealed three other cases of transitional cell carcinoma treated with bilateral nephrectomies. Based on our experience and the review of current literature, we recommend a waiting period of 2 years on dialysis post-operatively before proceeding to transplantation.
RESUMO
The four antiandrogens currently available (cyproterone acetate, flutamide, nilutamide and bilcalutamide) are reviewed relative to their structure, pharmacology and clinical effect.
