Collagen degradation products measured in serum can separate ovarian and breast cancer patients from healthy controls: A preliminary study

Abstract

Abstract. BACKGROUND: During cancer the otherwise tightly controlled homeostasis of the extracellular matrix (ECM) is disturbed. The protein composition changes, the ECM stiffens and increased levels of proteases are secreted. The combination of these processes result in release of specific protein fragments (e.g. collagens) to the circulation, which when measured may reflect disease pathogenesis. OBJECTIVE: To investigate if biomarkers of protease-degraded collagen could differentiate ovarian and breast cancer patients from healthy controls when measured in serum. METHODS: The levels of markers reflecting MMP-degradation of type I (C1M), type III (C3M) and type IV (C4M, C4M12) collagen were assessed in serum from ovarian cancer patients (n = 10), breast cancer patients (n = 14) and healthy controls (n = 49) using validated ELISAs. The markers were compared using one way ANOVA and AUC was calculated. RESULTS: All markers were significantly elevated in serum from ovarian cancer patients (p < 0.0001) and breast cancer patients (p < 0.04-0.0001) compared to healthy controls. Furthermore, diagnostically the markers were able to differentiate ovarian (AUROC 90%-93%) and breast cancer patients (AUROC 76%-93%) from healthy controls, with C1M being the strongest differentiator of disease vs. controls. CONCLUSION: Four serum biomarkers reflecting altered MMP-mediated collagen turnover were able to differentiate ovarian and breast cancer patients from healthy controls.Keywords: Cancer, extracellular matrix, collagen, biomarkers, breast cancer, ovarian cancer, matrix metalloproteinase, degradation, remodeling, tumor microenvironment BackgroundWomen's health is significantly influenced by the occurrence of cancers, such as breast and ovarian can- cers. Breast cancer is the leading cause of cancer death among women in the US and EU [1,2], and ovarian cancer, although less frequent, is often discovered in the late clinical stages where the cancer has already spread and no curative interventions are possible [3]. Taken together, the medical needs for breast and ovarian cancer are early diagnosis, prognosis and prediction of a therapeutic response. One of the best ways to achieve this is to use serum biomarkers [4].

The transcriptional signature of human ovarian carcinoma macrophages is associated with extracellular matrix reorganization

“…Furthermore, previous proteomic profiling of ovarian cancer ascites identified several proteins relevant in this context, including multiple collagens and lumican [55]. In addition, collagen type I, III and IV fragments have been found at elevated levels in serum samples from ovarian cancer patients [56]. …”

Remodeling of the Tumor Microenvironment Predicts Increased Risk of Cancer in Postmenopausal Women: The Prospective Epidemiologic Risk Factor (PERF I) Study

“…We have previously seen that C1M, C4M, and VICM levels are elevated in serum of cancer patients compared with serum levels measured in healthy controls (21,23,24), but it is not known if these biomarkers are elevated prior to the diagnosis of cancer. The aim of this study was to investigate whether levels of C1M, C4M, and VICM in serum samples collected in a large prospective study of postmenopausal women could be used as predictors of increased risk of cancer.…”

Somatostatin Octapeptide Inhibits Cell Invasion and Metastasis in Hepatocellular Carcinoma Through PEBP1

“…MMPs are zinc-dependent endopeptidases involved in the degradation of extracellular matrix (ECM), and thus promote tumor metastasis [27]. Our results suggested that octreotide might regulate the MMP2-TIMP2 pathway (but not the MMP9-TIMP1 pathway) to influence cell invasion and metastasis.…”