DFF45/ICAD表达降低与食管癌患者的不良预后相关。

Decreased expression of DFF45/ICAD is correlated with a poor prognosis in patients with esophageal carcinoma.

作者信息

Konishi Shigeru, Ishiguro Hideyuki, Shibata Yasuyuki, Kudo Junzo, Terashita Yukio, Sugiura Hironori, Koyama Hiroshi, Kimura Masahiro, Sato Atsushi, Shinoda Noriyuki, Kuwabara Yoshiyuki, Fujii Yoshitaka

机构信息

Department of Surgery II, Nagoya City University Medical School, Mizuho-ku, Japan.

出版信息

Cancer. 2002 Dec 15;95(12):2473-8. doi: 10.1002/cncr.10987.

DOI:10.1002/cncr.10987

PMID:12467059

Abstract

BACKGROUND

DNA fragmentation factor 45 (DFF45)/inhibotor of caspase activated DNAse (ICAD) forms a complex with DFF40/CAD and inhibits its DNA cleaving function during apoptosis. DFF45 also functions as a chaperone for native DFF40 and is necessary for its function. It has been indicated that defects in the apoptotic pathway may exist in neoplastic cells.

METHODS

The authors investigated mRNA expression of DFF45 in a series of 46 esophageal squamous cell carcinoma (ESCC) specimens using polymerase chain reaction amplification. The results were correlated with the patients' clinicopathologic characteristics.

RESULTS

DFF45 mRNA expression was significantly lower in tumors with higher pathologic stage, higher tumor status (T status), lymph node metastasis, or more extensive lymphatic invasion. Patients who had low DFF45 mRNA expression (indicated by the ratio of DFF45 mRNA expression in tumor to DFF45 mRNA expression in normal esophageal mucosa [tumor:normal] < 1) had a significantly shorter survival after undergoing surgery compared with patients who had high DFF45 mRNA expression (tumor:normal > 1, P = 0.0006; log-rank test, P = 0.0003; median follow-up, 14.6 months).

CONCLUSIONS

Patients with ESCC with decreased DFF45 mRNA expression levels had a poor prognosis compared with patients who had high DFF45 mRNA expression levels.

摘要

背景

DNA片段化因子45（DFF45）/半胱天冬酶激活的脱氧核糖核酸酶抑制剂（ICAD）与DFF40/CAD形成复合物，并在细胞凋亡过程中抑制其DNA切割功能。DFF45还作为天然DFF40的伴侣蛋白发挥作用，并且对其功能是必需的。已有研究表明肿瘤细胞中可能存在凋亡途径缺陷。

方法

作者使用聚合酶链反应扩增法研究了46例食管鳞状细胞癌（ESCC）标本中DFF45的mRNA表达情况。将结果与患者的临床病理特征进行关联分析。

结果

在病理分期较高、肿瘤状态（T分期）较高、有淋巴结转移或有更广泛淋巴浸润的肿瘤中，DFF45 mRNA表达显著降低。与DFF45 mRNA高表达患者（肿瘤：正常>1，P = 0.0006；对数秩检验，P = 0.0003；中位随访时间14.6个月）相比，DFF45 mRNA低表达患者（以肿瘤中DFF45 mRNA表达与正常食管黏膜中DFF45 mRNA表达之比[肿瘤：正常]<1表示）术后生存期显著缩短。