Gene expression profile of renal cell carcinoma clear cell type

Marcos F Dall’Oglio,Rafael F Coelho,Juliana M Sousa-Canavez,Miguel Srougi,Katia R M Leite,Paulo S L Oliveira

doi:10.1590/s1677-55382010000400004

Abstract

The determination of prognosis in patients with renal cell carcinoma (RCC) is based, classically, on stage and histopathological aspects. The metastatic disease develops in one third of patients after surgery, even in localized tumors. There are few options for treating those patients, and even the new target designed drugs have shown low rates of success in controlling disease progression. Few studies used high throughput genomic analysis in renal cell carcinoma for determination of prognosis. This study is focused on the identification of gene expression signatures in tissues of low-risk, high-risk and metastatic RCC clear cell type (RCC-CCT). We analyzed the expression of approximately 55,000 distinct transcripts using the Whole Genome microarray platform hybridized with RNA extracted from 19 patients submitted to surgery to treat RCC-CCT with different clinical outcomes. They were divided into three groups (1) low risk, characterized by pT1, Fuhrman grade 1 or 2, no microvascular invasion RCC; (2) high risk, pT2-3, Fuhrman grade 3 or 4 with, necrosis and microvascular invasion present and (3) metastatic RCC-CCT. Normal renal tissue was used as control. After comparison of differentially expressed genes among low-risk, high-risk and metastatic groups, we identified a group of common genes characterizing metastatic disease. Among them Interleukin-8 and Heat shock protein 70 were over-expressed in metastasis and validated by real-time polymerase chain reaction. These findings can be used as a starting point to generate molecular markers of RCC-CCT as well as a target for the development of innovative therapies.

Highlights

Renal cell carcinoma (RCC) accounts for approximately 5% of all malignancies and is considered the most lethal urological cancer [1,2]
Group 1 was composed of five men and two women submitted to tumor resection or partial nephrectomy; mean age 53.3 years-old, pT1, mean tumor size of 3.7 cm, Fuhrman grade 1 or 2, no microvascular invasion or necrosis
Group 2 was constituted of four males and one female submitted to radical nephrectomy, mean age 60 years-old, T2-3 mean tumor size of 8.2 cm, Fuhrman grade 3 or 4 with necrosis and microvascular invasion present

Summary

Introduction

Renal cell carcinoma (RCC) accounts for approximately 5% of all malignancies and is considered the most lethal urological cancer [1,2]. At early stages, it can be curable by surgical resection, but no effective treatment option is available for patients at advanced stage. Treatment options available for patients with metastatic disease are very limited and currently target therapy has been developed based on molecular peculiarities of RCC. Transcriptional profiling has emerged as a powerful approach to identify the molecular mechanism underlying renal carcinogenesis and in predicting clinical outcomes [5]. Gene expression profile may help to identify new biomarkers of aggressiveness and prognosis, selecting patients who could benefit from ancillary therapy. Microarray-based expression profiles have become a standard methodology in any high-throughput analysis

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