Correlation Between Baseline Osteoprotegerin Serum Levels and Prognosis of Advanced-Stage Colorectal Cancer Patients

Abstract

Background/Aims: Osteoprotegerin (OPG) is a soluble receptor of the pro-apoptotic cytokine TRAIL which is thought to contribute to tumour development by inhibiting apoptosis or affecting other aspects of tumour biology, including cell proliferation and immune response. Although immunohistochemical studies suggest that OPG correlates with survival in metastatic colorectal cancer (mCRC), only scarce data are available on serum OPG in CRC patients. Methods: In this pilot study, we assessed the prognostic significance of serum OPG and CEA (Carcinoembryonic antigen) in 81 patients with UICC (Union for International Cancer Control) stage-IV mCRC. OPG was additionally assessed by immunohistochemistry in primary tissue samples from 33 patients of the same cohort. Results: Baseline serum OPG correlated with CEA (r=0.36, p=0.0011), but independently predicted survival of mCRC patients. Life expectancy was poorer in patients with OPG levels above the median concentration of 51ng/ml (median overall survival [95% confidence interval] 1.8 years [1.3-3.0] vs. 1.0 [0.7-1.2] p=0.013). Patients with high levels of both OPG and CEA had an even poorer life expectancy vs. low-OPG/low-CEA patients (0.9 years [0.6-1.5] vs. 3 years [1.2-4.4], p=0.015), indicating that CEA and OPG have additive prognostic significance. Immunohistochemical analysis of OPG failed to show a correlation between OPG staining and survival (p=0.055) or OPG concentration from matched serum samples. Conclusions: This pilot study provides evidence of independent prognostic significance of serum OPG in patients with advanced mCRC and warrants its further prospective validation.

Prognostic Value of RANKL/OPG Serum Levels and Disseminated Tumor Cells in Nonmetastatic Breast Cancer

“…However, OPG can also act as an inhibitor of TRAIL, which induces tumor cell apoptosis (30) and high levels of OPG were associated with a higher cancer-related mortality in a large observational study with more than 6,000 patients (31). High levels of OPG have conferred a poor prognosis in patients with metastatic colorectal cancer (32). In prostate cancer, increased levels of OPG have been observed in patients with advanced cancer (33,34).…”

Chronic Obstructive Pulmonary Disease and Its Acute Exacerbation before Colon Adenocarcinoma Treatment Are Associated with Higher Mortality: A Propensity Score-Matched, Nationwide, Population-Based Cohort Study

“…Increased serum levels of IL-8 because of polymorphisms in the IL-8/CXCR2 genes were associated with disease progression, disease recurrence, and drug resistance [ 43 , 44 , 45 , 46 ]. Furthermore, patients with COPD with frequent exacerbations were reported to have high levels of inflammatory markers, such as CRP [ 47 ], fibrinogen [ 47 ], IL-6 [ 48 ], soluble tumor necrosis factor-α receptors [ 37 , 49 , 50 ], and osteoprotegrin [ 37 ], which have been shown to be associated with the survival of patients with colorectal cancer [ 39 , 40 , 41 , 42 , 51 , 52 , 53 , 54 ]. In summary, the findings of our study are in line with those of previous studies regarding the COPD spillover hypothesis.…”

Prognostic Value of Serum Osteoprotegerin Level in Patients With Hepatocellular Carcinoma Following Surgical Resection

“…By this way, OPG can prevent tumor cell apoptosis and prolong cells’ survival time, which may partly explain the association between OPG and patients’ prognosis. In addition, it was reported that serum OPG levels were elevated in patients with advanced colorectal cancer (CRC) ( 19 ). Overexpression of OPG in CRC tissues was closely related with increased risk of tumor relapse and death, which was suggested as a potential prognostic biomarker for CRC patients.…”