Serum Cartilage Oligomeric Matrix Protein and Golgi Protein-73: New Diagnostic and Predictive Tools for Liver Fibrosis and Hepatocellular Cancer?

Abstract

The cartilage oligomeric matrix protein (COMP) and Golgi-protein-73 (GP73) have been proposed as markers of liver fibrosis and hepatocellular carcinoma (HCC). Our aim was to assess the performance of the combination of these markers in diagnosing cirrhosis and predicting HCC development. Sera from 288 consecutive patients with chronic liver diseases were investigated by using COMP and GP73-ELISAs. Dual positivity for COMP (>15 U/L) and GP73 (>20 units) was observed in 24 (8.3%) patients, while 30 (10.4%) were GP73(+)/COMP(−), 37/288 (12.8%) GP73(−)/COMP(+), and 197 (68.5%) GP73(−)/COMP(−). Positivity for both markers was associated with cirrhosis [23/24 (95.8%) for GP73(+)/COMP(+) vs. 22/30 (73.3%) for GP73(+)/COMP(−) vs. 25/37 (67.6%) for GP73(−)/COMP(+) vs. 46/197 (23.4%) for GP73(−)/COMP(−); P < 0.001]. The combination of GP73, COMP, the aspartate aminotransferase/platelets ratio index, and the Fibrosis-4 score had even higher diagnostic accuracy to detect the presence of cirrhosis [AUC (95% CI): 0.916 (0.878–0.946)] or significant liver fibrosis (METAVIR ≥ F2) [AUC (95% CI): 0.832 (0.768–0.883)] than each marker alone. Kaplan-Meier analysis showed that positivity for both GP73 and COMP was associated with higher rates of HCC development (P < 0.001) and liver-related deaths (P < 0.001) during follow-up. In conclusion, the combination of GP73 and COMP seems efficient to detect cirrhosis and predict worse outcomes and the development of HCC in patients with chronic liver diseases.

A meta-analysis and of clinical values of 11 blood biomarkers, such as AFP, DCP, and GP73 for diagnosis of hepatocellular carcinoma

“…Gatselis et al. reported that the combination of GP73 and the cartilage oligomeric matrix protein (COMP) seems efficient to detect the development of HCC in patients with chronic liver diseases [ 98 ].…”

Long-term results of mycophenolate mofetil vs. azathioprine use in individuals with autoimmune hepatitis

“… 28 In individuals with cirrhosis who had not undergone liver biopsy, the diagnosis was based on clinical findings of decompensated disease, and/or supportive ultrasonography (coarse echo pattern of the parenchyma in association with irregular hepatic margins, spleen >12 cm, portal vein >16 mm), and/or liver stiffness measurements (LSM) using FibroScan® 502 (Echosens, Paris, France) >9 kPa, and/or endoscopic findings of portal hypertension, as we have reported recently. 29 , 30 …”

Cartilage Oligomeric Matrix Protein, Diseases, and Therapeutic Opportunities

“…Elevated serum COMP is strongly associated with hepatocellular carcinoma (HCC) progression [ 95 ], suggesting that it can be used for non-invasive assessments of HCC progression. Moreover, the combination of COMP and GP73 showed a pronounced performance in detecting severe fibrosis/cirrhosis and predicting the development of HCC in patients with chronic liver diseases [ 30 ]. A recent study also showed that a multi-marker panel (AFP and PIVKA-II, with either IGFBP3, COMP or MMP3, plus age and sex) is efficient for the detection of early- and all-stage HCC [ 96 ].…”

“…Serum COMP has been demonstrated to be a sensitive non-invasive diagnostic biomarker for liver fibrosis [ 122 ]. Gatselis et al discovered that serum COMP is efficient to detect cirrhosis in the patients with chronic liver diseases [ 30 ].…”

“…Due to the protective effects of COMP on cartilage, a thorough understanding of COMP functions and the related signaling pathways is beneficial for novel therapeutic strategies for cartilage degradation diseases. Recent exciting achievements have implied that COMP is an important gene contributing to other diseases, such as cancer/malignancy [ 22 , 23 , 24 ], cardiovascular diseases [ 25 , 26 , 27 ], and fibrosis [ 28 , 29 , 30 ]. These findings renewed our understanding of COMP functions and ECM biology beyond skeleton.…”