title: Improved tumour marker sensitivity in detecting colorectal liver metastases by combined type IV collagen and CEA measurement.
abstract: Carcinoembryonic antigen (CEA) is the best circulating tumour marker for colorectal liver metastasis (CLM) but has suboptimal sensitivity and specificity. Circulating type IV collagen (COLIV) is a new potential CLM marker. Here, COLIV and CEA were measured in patients with resectable CLM. COLIV levels were also related to the type of CLM. The prognostic value of these markers and the type of CLM on survival was evaluated. Preoperative plasma samples (n = 94) from patients (n = 85) with CLM undergoing liver resection were used. Seven patients underwent repeated liver resection. Samples from 118 healthy individuals served as control. Samples after liver resection (n = 27) were analysed and related to recurrence. COLIV and CEA levels were analysed, and the type of CLM was classified using paraffinated tissue. Results were analysed by logistic regression and receiver operating characteristic (ROC) curve analysis. CLM patients had significantly elevated levels of COLIV compared to controls (p = 0.001). The sensitivity of COLIV was not better than CEA, but improved sensitivity for detecting CLM was observed with a combination of the two markers compared to using either marker alone (p = 0.001). Circulating COLIV was elevated in 81 % and CEA in 56 % of CLM patients at diagnosis, and high marker levels were related to poor survival. In follow-up samples (n = 27), patients with CLM recurrence (n = 14) had significantly elevated COLIV levels compared to patients without postoperative recurrence (n = 10) (p = 0.001). COLIV is a promising tumour marker for CLM and can possibly be used to detect postoperative CLM recurrence. The combination of COLIV and CEA is superior to either marker alone in detecting CLM.
authors.affiliation: Department of Surgical and Perioperative Sciences, Surgery, Umeå University, 90185, Umeå, Sweden. hanna.nystrom@umu.se.
authors.forename: Hanna
authors.initials: H
authors.lastname: Nyström
authors.affiliation: Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden.
authors.forename: Björn
authors.initials: B
authors.lastname: Tavelin
authors.affiliation: Department of Surgical and Perioperative Sciences, Surgery, Umeå University, 90185, Umeå, Sweden.
authors.forename: Moa
authors.initials: M
authors.lastname: Björklund
authors.affiliation: Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Naredi
authors.affiliation: Department of Surgical and Perioperative Sciences, Surgery, Umeå University, 90185, Umeå, Sweden.
authors.forename: Malin
authors.initials: M
authors.lastname: Sund
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics; D002272:Carcinoembryonic Antigen / Q000097:blood* / Q000235:genetics; D024141:Collagen Type IV / Q000097:blood*; D015179:Colorectal Neoplasms / Q000097:blood* / Q000235:genetics / Q000473:pathology; D005109:Extracellular Matrix / Q000235:genetics; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology / Q000556:secondary; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000473:pathology; D009360:Neoplastic Cells, Circulating; D011184:Postoperative Period; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen; D024141:Collagen Type IV
keywords: CEA; Circulating biomarkers; Colorectal liver metastases; Extracellular matrix; Type IV collagen