Clinical significance of stromal apoptosis in colorectal cancer.

Clinical significance of stromal apoptosis in colorectal cancer.
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DOI:
10.1038/sj.bjc.6605220
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发表时间:
2009-09-01
影响因子:
8.8
通讯作者:
--
中科院分区:
医学1区
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--
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上皮细胞和基质细胞在结直肠癌的发生发展中起着重要作用。我们的目的是确定大肠癌上皮细胞和间质细胞凋亡的预后意义。总细胞凋亡测定caspase-3活性的蛋白质匀浆的CRC标本和211例CRC患者的邻近正常粘膜的测量。上皮细胞凋亡通过特异于半胱天冬酶-3降解的细胞角蛋白18产物(M30抗原)的ELISA测定。间质细胞凋亡由总细胞凋亡和上皮细胞凋亡之间的比率确定。与相应的邻近正常粘膜相比,大肠癌中上皮和间质细胞凋亡以及总细胞凋亡显著增加。低的肿瘤细胞凋亡总量(半胱天冬酶-3活性中位数)与疾病复发显著恶化相关(风险比(HR),95%置信区间(95% CI):1.77(1.05-3.01)),与临床病理学参数无关。上皮细胞凋亡与临床结局无关。相反,低基质细胞凋亡(中位半胱氨酸蛋白酶-3/M30)被发现是总生存期、无病生存期和疾病复发的独立预后因素,HR(95%CI)分别为1.66(1.17-2.35)、1.62(1.15-2.29)和1.69(1.01-2.85)。与上皮细胞凋亡相反,间质细胞凋亡是CRC生存和疾病复发的重要因素。
Epithelial and stromal cells play an important role in the development of colorectal cancer (CRC). We aimed to determine the prognostic significance of both epithelial and stromal cell apoptosis in CRC. Total apoptosis was determined by caspase-3 activity measurements in protein homogenates of CRC specimens and adjacent normal mucosa of 211 CRC patients. Epithelial apoptosis was determined by an ELISA specific for a caspase-3-degraded cytokeratin 18 product, the M30 antigen. Stromal apoptosis was determined from the ratio between total and epithelial apoptosis. Epithelial and stromal apoptosis, as well as total apoptosis, were significantly higher in CRC compared with corresponding adjacent normal mucosa. Low total tumour apoptosis (⩽median caspase-3 activity) was associated with a significantly worse disease recurrence (hazard ratio (HR), 95% confidence interval (95% CI): 1.77 (1.05–3.01)), independent of clinocopathological parameters. Epithelial apoptosis was not associated with clinical outcome. In contrast, low stromal apoptosis (⩽median caspase-3/M30) was found to be an independent prognostic factor for overall survival, disease-free survival and disease recurrence, with HRs (95% CI) of 1.66 (1.17–2.35), 1.62 (1.15–2.29) and 1.69 (1.01–2.85), respectively. Stromal apoptosis, in contrast to epithelial apoptosis, is an important factor with respect to survival and disease-recurrence in CRC.
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