Down-regulation of S100C is associated with bladder cancer progression and poor survival.
Down-regulation of S100C is associated with bladder cancer progression and poor survival.
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发表时间：
2005-01
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通讯作者：
A. Memon;B. Sørensen;P. Meldgaard;L. Fokdal;T. Thykjaer;E. Nexo
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作者：
A. Memon;B. Sørensen;P. Meldgaard;L. Fokdal;T. Thykjaer;E. Nexo
本研究的目的是鉴定在膀胱癌进展过程中下调的蛋白质。实验设计通过使用比较蛋白质组分析和mRNA的测量，我们发现与RT 4（1级）膀胱癌细胞系相比，T24（3级）中S100 C（蛋白质S100家族的成员）的显著下调。此外，mRNA水平的定量显示，蛋白质表达的降低反映了S100 C基因的低水平转录。基于这一观察结果，我们用实时PCR定量了88例患者膀胱癌活检样本中S100 C mRNA的表达水平，随访时间中位数为23个月（范围，1-97个月）。结果结缔组织浸润性肿瘤（T1，P = 0.0030）和肌肉浸润性肿瘤（T2-T4，P < 0.0001）中S100 C mRNA的表达明显低于浅表肿瘤（Ta）。S100 C与组织病理学分级呈负相关（P = 0.0003）。乳头状瘤中S100 C的表达明显高于实体瘤（P < 0.0001）。重要的是，我们发现S100 C的缺失与膀胱癌患者的生存率相关（P = 0.0006）。结论：我们的研究结果表明，S100 C的低表达与膀胱癌患者的生存率低有关。此外，与Ta期肿瘤相比，T1期肿瘤中S100 C的缺失强调了S100 C表达在膀胱癌发展早期受到抑制。
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.