Division of Colon and Rectal Surgery, Department of Surgery, St Luke-Roosevelt Hospital Center, Suite 7B, 425 West, 59th Street, New York, NY 10019, USA.
Surg Endosc. 2012 Oct;26(10):2751-7. doi: 10.1007/s00464-012-2269-5. Epub 2012 May 2.
Surgery has been associated with proangiogenic plasma protein changes that may promote tumor growth. Angiopoietin-like protein 4 (ANGPTL4) is expressed by endothelial cells and other tissues in response to hypoxia. Both intact ANGPTL4 and its partly degraded C-terminal fragment may promote tumor angiogenesis. This study had two purposes: to measure and compare preoperative plasma ANGPTL4 levels in patients with colorectal cancer (CRC) and benign colorectal disease (BCD) and to determine plasma levels after minimally invasive colorectal resection (MICR) for CRC.
Plasma was obtained from an IRB-approved plasma/data bank. Preoperative plasma ANGPTL4 levels were measured for CRC and BCD patients, but postoperative levels were determined only for CRC patients for whom a preoperative, a postoperative day (POD) 3, and at least one late postoperative sample (POD 7-55) were available. Late samples were bundled into four time blocks and considered as single time points. ANGPTL4 levels (mean ± SD) were measured via ELISA and compared (significance, p < 0.01 after Bonferroni correction).
Eighty CRC (71 % colon, 29 % rectal) and 60 BCD (62 % diverticulitis, 38 % adenoma) patients were studied. The mean preoperative plasma ANGPTL4 level in CRC patients (247.2 ± 230.7 ng/ml) was lower than the BCD group result (330.8 ± 239.0 ng/ml, p = 0.01). There was an inverse relationship between plasma levels and advanced CRC as judged by three criteria. In regard to the postoperative CRC analysis, the "n" for each time point varied: lower plasma levels (p < 0.001) were noted on POD 3 (161.4 ± 140.4 ng/ml, n = 80), POD 7-13 (144.6 ± 134.5 ng/ml, n = 46), POD 14-20 (139.0 ± 117.8 ng/ml, n = 27), POD 21-27 (138.9 ± 202.4, n = 20), and POD 28-55 (160.1 ± 179.0, n = 42) when compared to preoperative results.
CRC is associated with lower preoperative plasma ANGPTL4 levels compared with BCD, and the levels may vary inversely with disease severity. After MICR for CRC, levels are significantly lower for over a month compared with the preoperative level; the cause for this persistent decrease is unclear. The implications of both the lower preoperative level and the persistently decreased postoperative levels are unclear. Further studies are needed.
手术与促进肿瘤生长的促血管生成血浆蛋白变化有关。血管生成素样蛋白 4（ANGPTL4）由内皮细胞和其他组织在缺氧时表达。完整的 ANGPTL4 及其部分降解的 C 端片段都可能促进肿瘤血管生成。本研究有两个目的：测量并比较结直肠癌（CRC）和良性结直肠疾病（BCD）患者术前血浆 ANGPTL4 水平，并确定 CRC 患者微创结直肠切除（MICR）术后的血浆水平。
从经 IRB 批准的血浆/数据银行获得血浆。对 CRC 和 BCD 患者进行术前血浆 ANGPTL4 水平测量，但仅对 CRC 患者进行术后水平测量，这些患者术前、术后第 3 天（POD3）以及至少有一个晚期术后样本（POD7-55）可用。晚期样本分为四个时间块并视为单个时间点。通过 ELISA 测量 ANGPTL4 水平（平均值±SD）并进行比较（在经过 Bonferroni 校正后具有统计学意义，p<0.01）。
共纳入 80 例 CRC（71%结肠癌，29%直肠癌）和 60 例 BCD（62%憩室炎，38%腺瘤）患者。CRC 患者术前平均血浆 ANGPTL4 水平（247.2±230.7ng/ml）低于 BCD 组（330.8±239.0ng/ml，p=0.01）。根据三个标准判断，血浆水平与晚期 CRC 呈负相关。关于术后 CRC 分析，每个时间点的“n”不同：POD3（161.4±140.4ng/ml，n=80）、POD7-13（144.6±134.5ng/ml，n=46）、POD14-20（139.0±117.8ng/ml，n=27）、POD21-27（138.9±202.4ng/ml，n=20）和 POD28-55（160.1±179.0ng/ml，n=42）时，血浆水平显著低于术前水平（p<0.001）。
与 BCD 相比，CRC 术前血浆 ANGPTL4 水平较低，且水平可能与疾病严重程度呈负相关。CRC 患者行 MICR 后，一个月以上的术后水平明显低于术前水平；这种持续下降的原因尚不清楚。术前水平较低和术后水平持续降低的意义尚不清楚。需要进一步研究。
