The Prospective Epidemiologic Risk Factor (PERF I) Study: A novel prognostic serum biomarker reflectingtype I collagen degradationis associated withtumor burden

Background:Matrix metalloproteinase (MMP) mediated degradation of the extracellular matrix (ECM) plays an important role in the development of cancer. One of the most abundant ECM proteins is type I collagen, which is commonly dysregulated and degraded duringtumorigenesis.We have identified a novel serum biomarker that reflects type I collagen degradation by MMP's (C1M).The aim of this study was to investigate if C1M could be used as a tool for early detection ofcancer both in relation to early diagnosis and tumor burden prognosis in a large prospective study.

Material and Methods: From 1999-2001, 5855 womenaged48-89 participated in the Prospective Epidemiologic Risk Factor (PERF I) study. Demographics and serum samples were collected at time of enrollment. Cancer diagnoses, including cancer stage were obtained from the Danish Cancer Registry ultimo 2014. Serum C1M (sC1M)levels were measured by ELISA in patients. The sC1M level in cancer patients diagnosed up to 400 days (mean days = 135.8) after blood draw was compared withnon-cancer diagnosed and non-diseased women (healthy). Cancer patients were sub grouped into three groups based on their cancer stage (localized, lymph node invasion and metastasized) and the levels of sC1M werecompared.Data were analyzed using a non-parametric t-test (Mann-Whitney) andone way ANOVA(Kruskal-Wallis).

Results:sC1M, at baseline, was significantly elevated in women diagnosed up to 400 days after blood draw compared to healthy women (p=0.0007) (see table).Furthermore, there was a clear trend towards elevated sC1Mwith increasing tumor burden (see table).sC1M wasable to discriminate between localized and metastasized cancer in women diagnosed up to 400 days after blood draw (p=0.04).

Conclusion: This study evaluated a novel ECM serum biomarker having potential as a new tool in early cancer diagnosis and prognosis.The ability of a biomarker to predict tumor burden is very important as this could improve treatment and thereby increase the overall survival rate in cancer patients. Further investigations into C1M as a diagnostic and prognostic marker for cancer are highly relevant.

Healthy
(95% CI)
N=3201 / Cancer diagnosed<400 days (95% CI)
N=120 / Localized
(95% CI)
N=76 / Lymph node invasion(95% CI)
N=31 / Metastasized(95% CI)
N=12
C1M (ng/ml) / 50.1 (48.9-51.4) / 61.4 (52.4-70.3) / 52.8 (45.8-59.7) / 75.5 (47.5-103.4) / 80.2 (46.5-113.8)

Keywords: Cancer, serum biomarker, extracellular matrix degradation

Kehlet SN, Bager CL, Willumsen N, Dragsbaek K, Neergaard JS, Hansen HB, Bay-Jensen A, Leeming DJ, Christiansen C, Karsdal M