Ahn Byung Kyu, Kim Sung Hoo, Paik Seung Sam, Lee Kang Hong
Department of Surgery, College of Medicine, Hanyang University, 222-1, Wangsimni-ro, Seongdong-gu, Seoul, 133-792, Korea.
Department of Pathology, College of Medicine, Hanyang University, Seoul, Korea.
Langenbecks Arch Surg. 2016 Dec;401(8):1203-1210. doi: 10.1007/s00423-016-1483-3. Epub 2016 Aug 2.
Apoptotic protease activating factor-1 (APAF-1) is a key regulator in the mitochondrial apoptotic pathway and an important diagnostic and therapeutic biomarker. Loss of APAF-1 expression has been observed in various tumors including colorectal cancer. The aim of our study was to evaluate the relationship between loss of APAF-1 expression and early recurrence of stage I-III colorectal cancer.
We investigated 165 out of 492 patients who had undergone curative resection for colorectal cancer between 1991 and 2001. Sixty-one patients (37.0 %) had early recurrence within 1 year after surgery. Tissue microarrays were used for immunohistochemical detection of APAF-1.
The mean age of patients with recurrence was 58 years (range, 24-85); 88 (53.3 %, 88/165) were male. APAF-1 was expressed in 32 (19.4 %, 32/165) cases and was not expressed in 133 (80.6 %, 133/165). In univariate analysis, early recurrence significantly correlated with loss of APAF-1 expression (p = 0.017), tumor stage (p = 0.005), N category (p = 0.001), and lymphatic invasion (p = 0.008). In a logistic regression model, loss of APAF-1 expression (p = 0.015, 95 % CI = 1.280-10.063) and N category (p = 0.001, 95 % CI = 0.004-0.739) proved to be independent risk factors associated with early recurrence. In patients with lymph node metastasis, early recurrence was more frequent in the APAF-1-negative group than in the APAF-1-positive group (46.2 % (54/117) vs. 22.2 % (6/27), p = 0.023).
Loss of APAF-1 expression is associated with early recurrence in stage I-III colorectal cancer, suggesting that APAF-1 may have clinical value as a predictive marker of early recurrence.
凋亡蛋白酶激活因子-1（APAF-1）是线粒体凋亡途径中的关键调节因子，也是重要的诊断和治疗生物标志物。在包括结直肠癌在内的多种肿瘤中均观察到APAF-1表达缺失。本研究旨在评估APAF-1表达缺失与I-III期结直肠癌早期复发之间的关系。
我们调查了1991年至2001年间接受结直肠癌根治性切除术的492例患者中的165例。61例患者（37.0%）在术后1年内出现早期复发。使用组织芯片进行APAF-1的免疫组化检测。
复发患者的平均年龄为58岁（范围24-85岁）；88例（53.3%，88/165）为男性。32例（19.4%，32/165）病例中APAF-1表达阳性，133例（80.6%，133/165）病例中APAF-1表达阴性。单因素分析中，早期复发与APAF-1表达缺失（p = 0.017）、肿瘤分期（p = 0.005）、N分期（p = 0.001）及淋巴浸润（p = 0.008）显著相关。在逻辑回归模型中，APAF-1表达缺失（p = 0.015，95%CI = 1.280-10.063）和N分期（p = 0.001，95%CI = 0.004-0.739）被证明是与早期复发相关的独立危险因素。在有淋巴结转移的患者中，APAF-1阴性组的早期复发比APAF-1阳性组更常见（46.2%（54/117）对22.2%（6/27），p = 0.023）。
APAF-1表达缺失与I-III期结直肠癌的早期复发相关，提示APAF-1可能作为早期复发的预测标志物具有临床价值。
