title: Plasma levels of angiopoietin-like protein 4 (ANGPTL4) are significantly lower preoperatively in colorectal cancer patients than in cancer-free patients and are further decreased during the first month after minimally invasive colorectal resection.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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).
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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. cmudiyanselage@chpnet.org
authors.forename: H M C
authors.initials: HM
authors.lastname: Shantha Kumara
authors.forename: Daniel
authors.initials: D
authors.lastname: Kirchoff
authors.forename: Sajith A
authors.initials: SA
authors.lastname: Herath
authors.forename: Joon Ho
authors.initials: JH
authors.lastname: Jang
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Yan
authors.forename: Michael
authors.initials: M
authors.lastname: Grieco
authors.forename: Vesna
authors.initials: V
authors.lastname: Cekic
authors.forename: Richard L
authors.initials: RL
authors.lastname: Whelan
mesh_terms: D000368:Aged; D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins / Q000097:blood*; D014408:Biomarkers, Tumor / Q000097:blood*; D003082:Colectomy / Q000706:statistics & numerical data; D003108:Colonic Diseases / Q000097:blood; D015179:Colorectal Neoplasms / Q000097:blood* / Q000601:surgery*; D005260:Female; D006801:Humans; D010535:Laparoscopy / Q000706:statistics & numerical data; D007902:Length of Stay; D008297:Male; D008875:Middle Aged; D019060:Minimally Invasive Surgical Procedures; D011184:Postoperative Period; D057234:Preoperative Period; D012002:Rectal Diseases / Q000097:blood
chemical_list: C474772:ANGPTL4 protein, human; D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins; D014408:Biomarkers, Tumor