Endo Kazuya, Kohnoe Shunji, Watanabe Akihiro, Tashiro Hideya, Sakata Hisanobu, Morita Masaru, Kakeji Yoshihiro, Maehara Yoshihiko
Department of Surgery and Science, Kyushu University, Fukuoka 812-8582, Japan.
Oncol Rep. 2009 Feb;21(2):351-5.
Second mitochondria-derived activator of caspases/direct inhibitor of apoptosis-binding protein with low pI (Smac/DIABLO) is released by mitochondria in response to apoptotic stimuli and is thought to regulate apoptosis by antagonizing inhibitors of apoptosis proteins, which play an important role in sensitization of cancer cells to various therapeutic regimens. The expression of Smac/DIABLO has been demonstrated in various cancer cells, though little is known about its clinical significance with respect to colorectal cancer. The current study was designed to evaluate the relationship between prognosis and Smac/DIABLO expression by clinicopathological analysis of patients with colorectal cancer. Smac/DIABLO expression was evaluated using immunohistochemical staining in 121 consecutive patients with colorectal cancer and the relationship between Smac/DIABLO expression and clinicopathological factors was analyzed. Smac/DIABLO-positive expression was detected in 80 of the 121 patients (66%). The incidence of lymph node and distant metastasis in Smac/DIABLO-negative cancer was significantly higher than that in Smac/DIABLO-positive cancer (P=0.0004 and P=0.003, respectively). While univariate analysis showed that survival in patients with Smac/DIABLO-negative expression was significantly poorer than in Smac/DIABLO-positive cases (P<0.0001), Smac/DIABLO-negative expression was a prognostic indicator independent of Dukes' staging and lymph node metastasis by multivariate analysis. This study proposes that the decrease of Smac/DIABLO expression is an independent factor determining the poorer prognosis of patients with colorectal cancer.
第二线粒体衍生的半胱天冬酶激活剂/低pI凋亡直接抑制因子结合蛋白（Smac/DIABLO）由线粒体在凋亡刺激下释放，被认为通过拮抗凋亡抑制蛋白来调节凋亡，而凋亡抑制蛋白在癌细胞对各种治疗方案的致敏中起重要作用。Smac/DIABLO的表达已在多种癌细胞中得到证实，尽管关于其在结直肠癌中的临床意义知之甚少。本研究旨在通过对结直肠癌患者的临床病理分析来评估预后与Smac/DIABLO表达之间的关系。采用免疫组织化学染色对121例连续的结直肠癌患者进行Smac/DIABLO表达评估，并分析Smac/DIABLO表达与临床病理因素之间的关系。121例患者中有80例（66%）检测到Smac/DIABLO阳性表达。Smac/DIABLO阴性癌的淋巴结转移和远处转移发生率显著高于Smac/DIABLO阳性癌（分别为P = 0.0004和P = 0.003）。单因素分析显示，Smac/DIABLO阴性表达患者的生存率显著低于Smac/DIABLO阳性患者（P < 0.0001），多因素分析表明Smac/DIABLO阴性表达是独立于Dukes分期和淋巴结转移的预后指标。本研究表明，Smac/DIABLO表达降低是决定结直肠癌患者预后较差的独立因素。
