凋亡蛋白酶激活因子-1（APAF-1）表达缺失与结直肠癌的肿瘤进展及不良预后相关。
Loss of APAF-1 expression is associated with tumour progression and adverse prognosis in colorectal cancer.
作者信息
Zlobec Inti, Minoo Parham, Baker Kristi, Haegert David, Khetani Karim, Tornillo Luigi, Terracciano Luigi, Jass Jeremy R, Lugli Alessandro
机构信息
Department of Pathology, McGill University, Duff Medical Building, 3775 University Street, Montreal, Canada H3A 2B4.
出版信息
Eur J Cancer. 2007 Apr;43(6):1101-7. doi: 10.1016/j.ejca.2007.01.029. Epub 2007 Mar 12.
The aim of this study was to determine the prognostic value of APAF-1 in colorectal cancer (CRC). Immunohistochemistry for APAF-1 was performed on a tissue microarray of 1015 mismatch-repair (MMR) proficient and 130 sporadic MLH1-negative CRCs. The association of APAF-1 with clinico-pathological features including 10-year survival time was analysed. Methylation specific PCR was performed on a subset of MMR-proficient and MLH1-negative CRC. Loss of APAF-1 was associated with advanced T stage (p-value=0.022), N stage (p-value=0.009), vascular invasion (p-value=0.001) and worse survival (p-value=0.017) in MMR-proficient CRC. In MLH1-negative CRC, loss of APAF-1 was associated with metastasis (p-value=0.041), worse prognosis (p-value<0.001) and independently predicted shorter survival time (p-value<0.001). No methylation was found in the selected region of APAF-1. APAF-1 is a marker of tumour progression in MMR-proficient CRC and an independent adverse prognostic factor in MLH1-negative CRC.
本研究的目的是确定APAF-1在结直肠癌（CRC）中的预后价值。对1015例错配修复（MMR）功能正常和130例散发性MLH1阴性的CRC组织芯片进行APAF-1免疫组织化学检测。分析APAF-1与包括10年生存时间在内的临床病理特征之间的关联。对MMR功能正常和MLH1阴性的CRC亚组进行甲基化特异性PCR检测。在MMR功能正常的CRC中，APAF-1缺失与T分期进展（p值 = 0.022）、N分期（p值 = 0.009）、血管侵犯（p值 = 0.001）及较差的生存率（p值 = 0.017）相关。在MLH1阴性的CRC中，APAF-1缺失与转移（p值 = 0.041）、更差的预后（p值<0.001）相关，且独立预测较短的生存时间（p值<0.001）。在APAF-1的选定区域未发现甲基化。APAF-1是MMR功能正常的CRC中肿瘤进展的标志物，也是MLH1阴性的CRC中独立的不良预后因素。
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