Vastatin (the NC1 domain of human type VIII collagen a1 chain) is linked to stromal reactivity and elevated in serum from patients with colorectal cancer

Cancer Biol Ther. 2019;20(5):692-699. doi: 10.1080/15384047.2018.1550571. Epub 2019 Jan 9.

Abstract

Vastatin, a fragment derived from type VIII collagen, is one of the least studied collagen-derived matrikines. Vastatin can be detected in serum but little is known regarding the relevance of serum vastatin in colorectal cancer (CRC). In this study, serum vastatin was measured (ELISA) in 67 healthy controls and 48 CRC patients prior to resection and compared to clinicopathological parameters and serum biomarkers of stromal reactivity (C3M, VICM). Impact of resection and chemotherapy were evaluated by comparing baseline values with a 3-month follow-up sample (n = 23). Serum vastatin was detectable in 114 of 115 subjects. At baseline vastatin was elevated in CRC compared to controls (P < 0.001) with a diagnostic accuracy (AUROC) of 0.865, p < 0.0001. Vastatin correlated with age in controls but not in patients with CRC; no association was seen with clinicopathological parameters. Vastatin was independently associated with C3M (stepwise linear regression coefficient 0.25, p = 0.046). Overall, no difference was seen in vastatin levels between baseline and follow-up. In conclusion, vastatin is elevated in serum from patients with CRC and correlate with interstitial matrix degradation (C3M). This indicates that vastatin is linked to stromal reactivity and suggests that vastatin has biomarker potential in CRC. The association with clinicopathological parameters and treatment effect needs further evaluation.

Keywords: CRC; ECM; biomarker; colorectal cancer; extracellular matrix; matrikine; serum; vastatin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / blood*
  • Biomarkers, Tumor / metabolism
  • Case-Control Studies
  • Chemotherapy, Adjuvant
  • Collagen Type VIII / blood*
  • Collagen Type VIII / metabolism
  • Colorectal Neoplasms / blood
  • Colorectal Neoplasms / diagnosis*
  • Colorectal Neoplasms / pathology
  • Colorectal Neoplasms / therapy
  • Extracellular Matrix / pathology*
  • Female
  • Follow-Up Studies
  • Healthy Volunteers
  • Humans
  • Male
  • Middle Aged
  • Young Adult

Substances

  • Biomarkers, Tumor
  • Col8A1 protein, human
  • Collagen Type VIII
  • vastatin