Prognostic significance of cyclinD1 amplification and the co-alteration of cyclinD1/pRb/ppRb in patients with esophageal squamous cell carcinoma
Prognostic significance of cyclinD1 amplification and the co-alteration of cyclinD1/pRb/ppRb in patients with esophageal squamous cell carcinoma
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DOI：
10.1111/j.1442-2050.2011.01291.x
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发表时间：
2012-09-01
影响因子：
2.6
通讯作者：
Wu, Y. -L.
中科院分区：
文献类型：
--
作者：
Wang, M. -T.;Chen, G.;Wu, Y. -L.
CyclinD1/pRb/ppRb是调控细胞周期的重要途径之一，与多种癌症的发生发展有关。然而，CyclinD1/pRb/ppRb在食管鳞状细胞癌中的共同改变尚不清楚。本研究旨在分析cyclinD1 (CCND1) DNA扩增及CCND1/pRb/ppRB共改变在食管鳞状细胞癌患者中的预后意义。采用实时定量逆转录聚合酶链反应和免疫组织化学分别检测100例肿瘤标本和11例正常组织中CCND1 DNA扩增和CCND1、pRb、ppRb蛋白表达。采用KaplanMeier法分析其预后意义。我们发现41%的患者有CCND1 DNA扩增，与没有CCND1扩增的患者相比，生存时间较短（25.63个月vs.未达到，P = 0.007）。CCND1+/pRb/ppRb+蛋白表达水平共变的患者总生存期较其他患者差（11.4个月vs 43.4个月，P = 0.001）。Cox回归分析显示，CCND1/pRb/ppRb和CyclinD1扩增的共变是食管癌患者最独立的预后因素。上述结果提示，CCND1的扩增和CCND1+/pRb/ppRb+的共交替可能在食管癌患者的预后评价中起着至关重要的作用，且CCND1+/pRb/ppRb+患者的预后最差。这些结果也提示CCND1扩增或CyclinD1+/pRb/ppRb+共突变的患者可能是未来针对CCND1/pRb/ppRb通路进行治疗的优势人群。
CyclinD1/pRb/ppRb is one of the most important pathways regulating the cell cycle, and related with the development of many cancers. However, the co-alteration of CyclinD1/pRb/ppRb in esophageal squamous cell carcinomas is less understood. This study aims to analyze the combined prognostic significance of cyclinD1 (CCND1) DNA amplification and the co-alteration of CCND1/pRb/ppRB in patients with esophageal squamous cell carcinoma. CCND1 DNA amplification and the protein expression of CCND1, pRb, and ppRb on 100 tumor specimens and 11 normal tissues were detected using real-time quantitative reverse transcription polymerase chain reaction and immunohistochemistry, respectively. Their prognosis significance was analyzed by KaplanMeier method. We found that 41% of the patients had CCND1 DNA amplification, which had a short survival time compared with the patients without CCND1 amplification (25.63 months vs. not reached, P = 0.007). The patients with the co-alternation of CCND1+/pRb/ppRb+ protein expression levels have a poorer overall survival than the others (11.4 vs. 43.4 months, P = 0.001). Cox regression analysis showed that the co-alternation of CCND1/pRb/ppRb and CyclinD1 amplification were the two most independent prognosis factors of patients with esophageal cancer. These findings suggested that CCND1 amplification and co-alternation of CCND1+/pRb/ppRb+ may play a crucial role in the prognostic evaluation of patients with esophageal cancer, and the patients with CCND1+/pRb/ppRb+ have the worst prognosis in all the patients. The results also indicated that the patients with CCND1 amplification or co-alternation of CyclinD1+/pRb/ppRb+ might be the preponderant people for therapy targeting the CCND1/pRb/ppRb pathway in the future.