Abstract
This retrospective study aimed to examine the expression and localization of SAM68 (Src-associated in mitosis, 68 kDa) in a larger cohort of surgical specimens of renal cell carcinoma and their correlation with the progression of human renal cell carcinoma. The protein and mRNA expression levels of SAM68 in normal renal tubular epithelial cells, renal cell carcinoma cell lines, as well as nine pairs of renal cell carcinoma and matched tumor-adjacent renal tissues were examined using reverse transcription-PCR and Western blot. Moreover, SAM68 protein expression and localization in 241 clinicopathologically characterized renal cell carcinoma samples were examined by immunohistochemistry. Prognostic and diagnostic associations were examined by statistical analyses. SAM68 was markedly overexpressed in renal cell carcinoma cell lines and renal cell carcinoma tissues at both the transcriptional and translational levels. Immunohistochemical analysis revealed high SAM68 protein expression in 129 of the 241 (53.5%) paraffin-embedded archival renal cell carcinoma specimens. Moreover, there was a significant correlation between SAM68 expression and pathologic stage (P < 0.001), T classification (P = 0.003), N classification (P = 0.001), M classification (P = 0.006), and Fuhrman grade (P < 0.001). Patients with higher SAM68 expression had shorter overall survival time than patients with lower SAM68 expression, and the cytoplasmic localization of SAM68 significantly correlated with clinicopathologic grade and outcome. Multivariate analysis indicated that SAM68 protein overexpression and cytoplasmic localization were independent predictors for poor survival of renal cell carcinoma patients. Our results suggest that SAM68 could represent a novel and useful prognostic marker for renal cell carcinoma. High SAM68 expression and cytoplasmic localization are associated with poor overall survival in renal cell carcinoma patients.
Highlights
Renal cell carcinoma is the most lethal of the common urologic cancers, accounting for about 3% of all adult malignancies
Reverse transcription-PCR (RT-PCR) and realtime RT-PCR analysis revealed that SAM68 transcription was significantly up-regulated, by up to 27.5-fold, in renal cell carcinoma cell lines compared with normal renal tubular epithelial cells (Fig. 1B)
To examine further whether SAM68 up-regulation in renal cell carcinoma cell lines correlates with clinical progression, the expression of SAM68 was determined in nine pairs of renal cell carcinoma and adjacent normal renal tissues obtained from the same patient, using RT-PCR and Western blotting analyses
Summary
Renal cell carcinoma is the most lethal of the common urologic cancers, accounting for about 3% of all adult malignancies. More than 40% of renal cell carcinoma patients have died of the cancer, whereas the mortality rates associated with other urologic cancers, such as prostate cancer and bladder cancer, have been about 20% for last two decades [1, 2]. 30% of renal cell carcinoma patients are diagnosed with late-stage disease (stage III-IV), and even with radical nephrectomy, or combined with immunotherapy and targeted therapy as adjunctive therapy, the prognosis has not been significantly improved [5]. Finding specific biomarkers for the diagnosis and prognosis of renal cell carcinoma, as well as novel therapeutic targets, is a priority.
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