Clinical Significance of CD133 and Hypoxia Inducible Factor-1α Gene Expression in Rectal Cancer after Preoperative Chemoradiotherapy
Clinical Significance of CD133 and Hypoxia Inducible Factor-1α Gene Expression in Rectal Cancer after Preoperative Chemoradiotherapy
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DOI：
10.1016/j.clon.2010.09.012
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发表时间：
2011-06-01
影响因子：
3.4
通讯作者：
Kusunoki, M.
中科院分区：
文献类型：
--
作者：
Saigusa, S.;Tanaka, K.;Kusunoki, M.
目的：直肠癌术前放化疗（CRT）后远处复发的机制尚未完全阐明。如果不减少术前CRT后的远处复发，生存率的进一步提高就无法实现。最近，有报道称缺氧条件与癌症干细胞的产生相关。因此，我们研究了CD 133和缺氧诱导因子-1 α（HIF-1 α）的表达之间的相关性，以及它们与临床outcome.Materials和方法：52例直肠癌患者进行术前CRT。CRT后残留的癌细胞从福尔马林固定的石蜡包埋标本中获得，使用显微解剖。使用实时逆转录聚合酶链反应测量CD 133（PROM 1）和HIF-1 α基因的表达水平。使用结肠癌细胞系评估表达与照射之间的相关性。免疫组化染色这些蛋白CRT后也investigated.Results：我们观察到显着的负相关性CD 133（PROM 1）和HIF-1 α基因的基因表达CRT后残留的癌细胞。CD 133基因表达升高与远处复发和无复发生存率低相关。HIF-1 α基因表达升高与总生存率差相关，在体外，照射后基因表达水平的变化呈相反模式。免疫组化分析表明，残留的癌细胞强烈表达CD 133和缺乏HIF-1 α expression.Conclusion：我们的研究结果表明，CD 133和HIF-1 α表达与CRT后肿瘤的再生长和远处复发。这些结果可能有助于澄清未来的癌症治疗的直肠癌患者接受术前CRT的发展。(C)2010年皇家放射科医师学院。由爱思唯尔有限公司出版。保留所有权利。
Aims: The mechanism of distant recurrence in rectal cancer after preoperative chemoradiotherapy (CRT) has yet to be fully elucidated. Further improvements in survival rates cannot be achieved without decreasing distant recurrence after preoperative CRT. Recently, it was reported that hypoxic conditions were correlated with cancer stem cell generation. Therefore, we investigated the correlation between the expression of CD133 and hypoxia inducible factor-1 alpha (HIF-1 alpha), and their association with clinical outcome.Materials and methods: Fifty-two patients with rectal cancer underwent preoperative CRT. Residual cancer cells after CRT were obtained from formalin-fixed paraffin-embedded specimens using micro-dissection. The expression levels of CD133 (PROM1) and HIF-1 alpha genes were measured using real-time reverse transcription polymerase chain reaction. The correlation between expression and irradiation was evaluated using colon cancer cell lines. Immunohistochemical staining of these proteins after CRT was also investigated.Results: We observed a significant inverse correlation between the gene expression of CD133 (PROM1) and HIF-1 alpha genes in residual cancer cells after CRT. Elevated CD133 gene expression was associated with distant recurrence and poor recurrence-free survival. Elevated HIF-1 alpha gene expression was associated with poor overall survival, in vitro, the change in gene expression levels after irradiation showed inverse patterns. Immunohistochemical analyses showed that residual cancer cells strongly expressed CD133 and lacked HIF-1 alpha expression.Conclusion: Our results suggest that CD133 and HIF-1 alpha expression is associated with tumour re-growth and distant recurrence after CRT. These results may assist in clarifying the development of future cancer therapeutics in rectal cancer patients undergoing preoperative CRT. (C) 2010 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.