Diagnostic Value of Telomere-Binding Proteins (TPP1, POT1) in Hepatocellular Carcinoma

Abstract

Background: Previous studies have indicated that telomere-binding proteins, like TPP1 (telomere protection protein 1) and POT1 (protection of telomeres 1) might be associated with the aggressive biological behavior and prognosis of hepatocellular carcinoma (HCC). This study assessed TPP1 and POT1 in patients with hepatitis, liver cirrhosis, and HCC, and then evaluated their diagnostic value to differentiate HCC from benign liver disease. Methods: Whole blood TPP1 and POT1 levels in healthy controls (n = 267), and patients with hepatitis B (n = 209), liver cirrhosis (n = 248), or HCC (n = 248) were measured by real-time reverse transcriptase-polymerase chain reaction and Western blotting. Receiver operating characteristic curve analysis evaluated the diagnostic value of TPP1 and POT1 in HCC. Results: TPP1 and POT1 levels in whole blood of HCC patients were higher than that those with benign liver disease (hepatitis B + liver cirrhosis) and healthy controls (p < 0.05). In addition, TPP1 and POT1 showed good diagnostic performance to distinguish HCC from healthy controls, with an area under the curve (AUC) of 0.86 for TPP1, a sensitivity of 81.63%, and a specificity of 86.50%. The AUC of POT1 was 0.87, the sensitivity was 81.79%, and the specificity was 87.20%. Moreover, the combined diagnosis effect was more accurate, the AUC of TPP1 + POT1 was 0.91, the sensitivity was 84.50%, and the specificity was 91.80%. Conclusions: TPP1 and POT1 are promising markers for distinguishing patients with HCC. HCC predictive accuracy could be improved significantly by the combination of TPP1 + POT1 with AFP (alpha-fetoprotein) or PIVKA-II (protein induced by vitamin K absence or antagonist-II).