Elevated CD133, but not VEGF or EGFR, as a predictive marker of distant recurrence after preoperative chemoradiotherapy in rectal cancer.
Elevated CD133, but not VEGF or EGFR, as a predictive marker of distant recurrence after preoperative chemoradiotherapy in rectal cancer.
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DOI：
10.3892/or_00000491
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发表时间：
2009-10
期刊：
影响因子：
4.2
通讯作者：
H. Yasuda;Koji Tanaka;S. Saigusa;Y. Toiyama;Y. Koike;Y. Okugawa;Takeshi Yokoe;A. Kawamoto;Y. Inoue;C. Miki;M. Kusunoki
中科院分区：
文献类型：
--
作者：
H. Yasuda;Koji Tanaka;S. Saigusa;Y. Toiyama;Y. Koike;Y. Okugawa;Takeshi Yokoe;A. Kawamoto;Y. Inoue;C. Miki;M. Kusunoki
CD133被认为是结肠癌干细胞（CSCs）的标记物。最近的研究表明，csc可能有助于癌症复发和对常规治疗的抵抗。本研究旨在评估CD133在直肠癌放化疗（CRT）后残留癌细胞中的作用。40例直肠癌患者行CRT后手术治疗。分离直肠癌细胞在CRT前（n=30）和CRT后（n=40）的总rna。采用实时逆转录聚合酶链反应检测肿瘤内CD133、血管内皮生长因子（VEGF）和表皮生长因子受体（EGFR）水平。同时观察CRT后CD133的免疫组化染色。crt后标本中残留癌细胞中的CD133高于基质细胞（p<0.0001）。CRT后标本CD133水平升高（p=0.0184），而VEGF和EGFR水平下降（p分别<0.0001和p=0.0002）。远端复发患者的crt后CD133高于无复发患者（p=0.0136）。crt后CD133升高与较差的无病生存相关（p=0.0168）。CRT后残余癌细胞细胞质及根尖/腔内膜CD133免疫组化染色。CRT后残留癌细胞中的CD133表达可能表明在假定的csc中存在治疗抗性表型。FFPE标本中CD133升高，而不是VEGF或EGFR升高，可能是直肠癌术前CRT后远处复发和生存率差的预测指标。
CD133 has been postulated to be a colon cancer stem cell (CSCs) marker. Recent investigations suggest that CSCs might contribute to cancer recurrence and resistance to conventional therapies. This study aimed to evaluate the role of CD133 in residual cancer cells after chemoradiotherapy (CRT) for rectal cancer. Forty patients with rectal cancer underwent CRT followed by surgery. Total RNAs of rectal cancer cells before (n=30) and after (n=40) CRT were isolated. Intratumoral CD133, vascular endothelial growth factor (VEGF), and epidermal growth factor receptor (EGFR) levels were measured using real-time reverse transcription polymerase chain reaction. Immunohistochemical staining of CD133 after CRT was also investigated. CD133 in residual cancer cells was higher than in stromal cells in post-CRT specimens (p<0.0001). The levels of CD133 were found to have increased in post-CRT specimens (p=0.0184), while VEGF and EGFR levels decreased during CRT (p<0.0001 and p=0.0002, respectively). Patients who developed distant recurrence had a higher post-CRT CD133 compared with those patients without recurrence (p=0.0136). Elevated post-CRT CD133 was associated with poor disease-free survival (p=0.0168). Immunohistochemical staining of the cytoplasmic and apical/endoluminal membranous CD133 was observed in residual cancer cells after CRT. CD133 expression in residual cancer cells after CRT may indicate a treatment resistant phenotype in putative CSCs. Elevated CD133, but not VEGF or EGFR, on FFPE specimens may be a predictive marker of distant recurrence and poor survival after preoperative CRT in rectal cancer.