Expression and cytoplasmic localization of SAM68 is a significant and independent prognostic marker for renal cell carcinoma.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Zhang
Zhiling
Z
State Key Laboratory of Oncology in Southern China and Department of Experimental Research, Cancer Center, Zhongshan School of Medicine, Guangzhou 510060, PR China.
Li
Jun
J
Zheng
Haiqing
H
Yu
Chunping
C
Chen
Jin
J
Liu
Zhuowei
Z
Li
Manzhi
M
Zeng
Musheng
M
Zhou
Fangjian
F
Song
Libing
L
D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015153:Blotting, Western; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D003593:Cytoplasm / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D018450:Disease Progression; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015999:Multivariate Analysis; D011379:Prognosis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D016601:RNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C489559:KHDRBS1 protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins