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Down-Regulation of S100C Is Associated with Bladder Cancer Progression and Poor Survival

Departments of ¹ Clinical Biochemistry and ² Oncology, AS, Aarhus University Hospital and ³ Department of Clinical Biochemistry, Skejby Hospital, Aarhus, Denmark

Requests for reprints: Ashfaque A. Memon, Department of Clinical Biochemistry, AS, Aarhus University Hospital, Norrebrogade 44, 8000 Aarhus C, Denmark. Phone: 45-89492901; Fax: 45-89493060; E-mail: amemo{at}akh.aaa.dk.

Purpose: The goal of this study was to identify proteins down-regulated during bladder cancer progression.

Experimental design: By using comparative proteome analysis and measurement of mRNA, we found a significant down-regulation of S100C, a member of the S100 family of proteins, in T24 (grade 3) as compared with RT4 (grade 1) bladder cancer cell lines. Moreover, quantification of the mRNA level revealed that decreased expression of the protein reflects a low level of transcription of the S100C gene. Based on this observation, we quantified the S100C mRNA expression level with real-time PCR in bladder cancer biopsy samples obtained from 88 patients followed for a median of 23 months (range, 1-97 months).

Results: We found a significantly lower mRNA expression of S100C in connective tissue invasive tumors (T1, P = 0.0030) and muscle invasive tumors [(T2-T4), P < 0.0001] compared with superficial tumors (Ta). A negative correlation between S100C and histopathologic grade (P = 0.0003) was also observed. Furthermore, the papillary type showed higher expression of S100C than did the solid type of the tumor (P < 0.0001). Importantly, we found that loss of S100C was associated with survival in bladder cancer patients (P = 0.0006).

Conclusions: Our results show that low expression of S100C is associated with poor survival in patients with bladder cancer. Furthermore, loss of S100C in T1 as compared with Ta stage tumors emphasize that S100C expression is suppressed early during bladder cancer development.

Key Words: S100C • calgizzarin • S100A11 • bladder cancer • patient survival

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