Caspase-3 activity, response to chemotherapy and clinical outcome in patients with colon cancer
Caspase-3 activity, response to chemotherapy and clinical outcome in patients with colon cancer
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DOI：
10.1007/s00384-007-0362-3
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发表时间：
2008-01-01
影响因子：
2.8
通讯作者：
Rafecas, Antoni
中科院分区：
文献类型：
--
作者：
de Oca, Javier;Azuara, Daniel;Rafecas, Antoni
细胞凋亡程度在结直肠癌中的预后价值存在争议。本研究评估caspase-3活性作为结肠癌患者接受5-氟尿嘧啶辅助化疗的预后因素的假定临床应用价值。我们评估了肿瘤和正常结肠组织中caspase-3样蛋白酶活性。研究样本取自54名患者。这些患者要么是III期癌症(Dukes C期)，要么是高危II期癌症(Dukes B2期，伴有邻近器官侵犯、淋巴管或血管浸润性或癌胚抗原[CEA]和GT；5)。中位随访时间为73个月。已有单因素分析探讨不同变量(年龄、性别、术前CEA、肿瘤大小、Dukes分期、血管侵犯、淋巴侵犯、肿瘤caspase-3活性和正常粘膜caspase-3活性)与化疗后肿瘤复发的关系。肿瘤组织中caspase-3活性的中位数是正常粘膜的两倍多(881vs40.6U，p=0.001)，两者之间存在显著相关性(r=0.34)。多因素分析显示，男性(OR=3.53[1.13~10.90]，p=0.02)、年龄(OR=1.09[1.01~1.18]，p=0.03)、Dukes分期(OR=1.93[1.01~3.70])、正常黏膜中caspase-3活性(OR=1.02[1.01~1.04]，p=0.017)、肿瘤组织中caspase-3活性(OR=1.02[1.01~1.03])是影响复发的显著预后因素。正常粘膜和肿瘤组织中caspase-3活性低是结肠癌患者接受5-氟尿嘧啶辅助治疗后肿瘤复发的独立预后因素，与较低的无瘤生存率和较高的复发率相关。
The prognostic value of the degree of apoptosis in colorectal cancer is controversial. This study evaluates the putative clinical usefulness of measuring caspase-3 activity as a prognostic factor in colonic cancer patients receiving 5-fluoracil adjuvant chemotherapy.We evaluated caspase-3-like protease activity in tumours and in normal colon tissue. Specimens were studied from 54 patients. These patients had either stage III cancer (Dukes stage C) or high-risk stage II cancer (Dukes stage B2 with invasion of adjacent organs, lymphatic or vascular infiltration or carcinoembryonic antigen [CEA]> 5). Median follow-up was 73 months. Univariate analysis was performed previously to explore the relation of different variables (age, sex, preoperative CEA, tumour size, Dukes stage, vascular invasion, lymphatic invasion, caspase-3 activity in tumour and caspase-3 activity in normal mucosa) as prognostic factors of tumour recurrence after chemotherapy treatment. Subsequently, a multivariate Cox regression model was performed.Median values of caspase-3 activity in tumours were more than twice those in normal mucosa (88.1 vs 40.6 U, p=0.001), showing a statistically significant correlation (r=0.34). Significant prognostic factors of recurrence in multivariate analysis were: male sex (odds ratio, OR=3.53 [1.13-10.90], p=0.02), age (OR=1.09 [1.01-1.18], p=0.03), Dukes stage (OR=1.93 [1.01-3.70]), caspase-3 activity in normal mucosa (OR=1.02 [1.01-1.04], p=0.017) and caspase-3 activity in tumour (OR=1.02 [1.01-1.03], p=0.013).Low caspase-3 activity in the normal mucosa and tumour are independent prognostic factors of tumour recurrence in patients receiving adjuvant 5-fluoracil-based treatment in colon cancer, correlating with poor disease-free survival and higher recurrence rate.