Memon Ashfaque Ahmed, Sorensen Boe Sandahl, Meldgaard Peter, Fokdal Lars, Thykjaer Thomas, Nexo Ebba
Department of Clinical Biochemistry, AS, Aarhus University Hospital, Norrebrogade 44, 8000 Aarhus C, Denmark.
Clin Cancer Res. 2005 Jan 15;11(2 Pt 1):606-11.
The goal of this study was to identify proteins down-regulated during bladder cancer progression.
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).
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).
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.
本研究的目的是鉴定在膀胱癌进展过程中下调的蛋白质。
通过比较蛋白质组分析和mRNA测量，我们发现与RT4（1级）膀胱癌细胞系相比，T24（3级）中S100家族蛋白质成员S100C显著下调。此外，mRNA水平的定量分析表明，该蛋白质表达的降低反映了S100C基因转录水平较低。基于这一观察结果，我们采用实时PCR对88例膀胱癌活检样本中的S100C mRNA表达水平进行了定量分析，这些患者的随访时间中位数为23个月（范围1 - 97个月）。
我们发现，与浅表性肿瘤（Ta）相比，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S100C的mRNA表达显著降低。还观察到S100C与组织病理学分级之间呈负相关（P = 0.0003）。此外，乳头状类型的肿瘤中S100C的表达高于实体型肿瘤（P < 0.0001）。重要的是，我们发现S100C的缺失与膀胱癌患者的生存率相关（P = 0.0006）。
我们的结果表明，S100C低表达与膀胱癌患者的不良生存相关。此外，与Ta期肿瘤相比，T1期肿瘤中S100C的缺失强调了S100C表达在膀胱癌发展早期就受到抑制。
