Elevated preoperative serum levels of collagen I carboxyterminal telopeptide predict better outcome in early-stage luminal-B-like (HER2-negative) and triple-negative subtypes of breast cancer

Abstract

Type 1 collagen is an important part of the extracellular matrix and changes in its metabolism and distribution are essential in breast cancer induction and progression. Serum concentrations of type 1 collagen synthesis (aminoterminal propeptide (PINP)) and degradation markers (carboxyterminal telopeptide (ICTP)) have previously been studied in early and metastatic breast cancer, but no data are available on specific breast cancer subtypes. We assayed 662 preoperative serum samples for PINP and ICTP and 109 postoperative serum samples for ICTP. The results were linked to prospectively collected clinical data and the cases were divided into breast cancer subtypes for survival analyses. The concentrations of both pre- and postoperative ICTP serum levels increased linearly from ductal in situ carcinoma to stage I–II tumors, stage III tumors, and finally to those with concomitant primary metastases (preoperative ICTP, p = 0.009; postoperative ICTP, p = 0.016). High-preoperative ICTP levels were associated with better breast cancer-specific survival in connection with luminal-B-like (HER2-negative) tumors (p = 0.017), which was confirmed in Cox regression analysis (relative risk = 3.127; 95% confidence interval = 1.081–9.049, p = 0.035), when T-class (relative risk = 4.049; 95% confidence interval = 1.263–12.981; p = 0.019) and nodal status (relative risk = 3.896; 95% confidence interval = 1.088–13.959; p = 0.037) were included in the analysis. In patients with triple-negative breast cancer, a high-preoperative ICTP level was a significant predictor of local relapse-free survival in univariate (p = 0.0020) and multivariate analyses (relative risk = 13.04; 95% confidence interval = 1.354–125.5; p = 0.026; for T-class, relative risk = 2.128 and 95% confidence interval = 0.297–15.23; p = 0.452; for N-class, relative risk = 0.332 and 95% confidence interval = 0.033–3.307; p = 0.347). A preoperatively elevated serum ICTP level appears to be an important marker of better prognosis in triple-negative breast cancer and luminal-B-like (HER2-negative) subtypes.

Antitumor and antioxidant activities of polysaccharides from the seaweed Durvillaea antarctica

“…MMP‐1 cleaves type I collagen and inhibits TIMP‐1 function. Type I collagen cross‐linked carboxy terminal telopeptide acts as matrikine and appears to be an important marker of better prognosis in some types of cancer (Jääskeläinen et al., 2019). Additionally, polysaccharides from D. antarctica overexpressed THBS1 and THBS2 proteins that are potent endogenous inhibitors of angiogenesis (Lawler & Lawler, 2012) and exert negative effects on cell migration involved in sprouting angiogenesis (Esser et al., 2017) and cancer development.…”

Tumor Microenvironment: Extracellular Matrix Alterations Influence Tumor Progression

“…ICTP level in serum from patients with esophageal squamous cell carcinoma significantly correlates with tumor progression variables, including TNM stages (≥T2, N1, and M1), TNM stage ≥II, and maximal tumor length greater than 50 mm (117). A high level of ICTP in preoperated patient serum appears to be an important marker of better prognosis in triple-negative breast cancer and luminal-B-like [human epidermal growth factor receptor (HER)2-negative] subtypes (118). The elevation of the cross-linked N-telopeptide of type I collagen (NTx) appears positively related with the development and progression of bone metastasis in lung cancer (119).…”

Targeting type I collagen for cancer treatment

“…Serum levels of ICTP increase in prostate cancer patients with bone metastases, and in combination with other detection markers can improve their positive‐prediction value 162,163 . A preoperatively elevated serum ICTP level appears to be an important marker of prognosis for patients with triple‐negative breast cancer and luminal‐B‐like subtypes 164 . Multiple myeloma is the second most common hematologic malignancy, in which serum ICTP has been a useful prognostic indicator 165 …”

“…162,163 A preoperatively elevated serum ICTP level appears to be an important marker of prognosis for patients with triple-negative breast cancer and luminal-B-like subtypes. 164 Multiple myeloma is the second most common hematologic malignancy, in which serum ICTP has been a useful prognostic indicator. 165 Type I collagen cross-linked amino-telopeptide (NTx) is a newly identified noninvasive bone resorption marker that is easily quantified in urine.…”