Soluble Axl Is a Novel Diagnostic Biomarker of Hepatocellular Carcinoma in Chinese Patients with Chronic Hepatitis B Virus Infection

Abstract

PurposeThe purpose of this study was to evaluate the diagnostic value of soluble Axl (sAxl) in hepatocellular carcinoma (HCC) in comparison with serum α-fetoprotein (AFP).Materials and MethodsEighty HCC patients, 80 liver cirrhosis patients (LC), 80 patients with hepatitis B virus (HBV) infection, and 80 healthy controls (HC) were enrolled. sAxl levels were measured by an enzyme-linked immunosorbent assay, serum AFP levelswere measured by an electrochemiluminescence immunoassay. Receiver operating characteristic (ROC) curves were used to evaluate diagnostic performances.ResultsThe results show that levels of sAxl were high expression in patients with HCC (p < 0.05), varied with disease state as follows: HCC > LC > HC > HBV. Logistic regression and ROC curve analysis identified the optimal cut-off for sAxl in differentiating all HCC and non-HCC patients was 1,202 pg/mL (area under the receiver operating characteristic [AUC], 0.888; 95% confidence interval [CI], 0.852 to 0.924) with sensitivity 95.0%, specificity 73.3%. Furthermore, differential diagnosis of early HCC with non-HCC patients for sAxl showed the optimal cut-off was 1,202 pg/mL (AUC, 0.881; 95% CI, 0.831 to 0.931; sensitivity, 94.1%; specificity, 73.3%). Among AFP-negative HCC patients with non-HCC patients, the cut-off was 1,301 pg/mL (AUC, 0.898; 95% CI, 0.854 to 0.942) with a sensitivity of 84.6%, a specificity of 76.3%. The optimal cut-off for sAxl in differentiating all HCC and chronic liver disease patients was 1,243 pg/mL (AUC, 0.840; 95% CI, 0.791 to 0.888) with sensitivity 93.8%, specificity 61.9%. The combination of AFP and sAxl increased diagnostic value for HCC.ConclusionsAxl outperforms AFP in detecting HCC, especially in early HCC and in AFP-negative HCC. Combination sAxl with AFP improved the specificity for early HCC diagnosis. In summary, sAxl is a candidate serum marker for diagnosing HCC.

RETRACTED ARTICLE: A meta-analysis and of clinical values of 11 blood biomarkers, such as AFP, DCP, and GP73 for diagnosis of hepatocellular carcinoma

“…Hsp90alpha keeps silent in normal cells while active in tumour cells. Midkine (MDK) is a secretory cytokine, which can participate in the occurrence and development of malignant tumours by promoting division, promoting angiogenesis, and antiapoptosis [ 14 , 15 ]. In recent years, there were more and more studies on the diagnostic value of the above biomarkers for HCC, so which biomarker had a better diagnostic value?…”

AXL Knock-Out in SNU475 Hepatocellular Carcinoma Cells Provides Evidence for Lethal Effect Associated with G2 Arrest and Polyploidization

“…Its expression in clinical samples correlated with advanced tumor stage, multiple tumors, a higher incidence of vascular invasion, recurrence of disease, and mortality [10,18,32]. In addition, serum soluble AXL protein levels were reported as a new biomarker for HCC [33][34][35]. Phenotypic effects of AXL expression in HCC cell lines have been studied by RNA interference-mediated knock-down experiments.…”

New Blood Biomarkers for the Diagnosis of AFP-Negative Hepatocellular Carcinoma

“…In ANHC, sAxl was also indicated as a valid diagnostic biomarker (AUROC 0.803, sensitivity 73.0%, and specificity 70.8%), and in very early ANHC, sAxl presented an even higher diagnostic value (AUROC 0.863, sensitivity 80%, and specificity 69.2%) ( 113 ). A recent study also found that sAxl had an AUROC of 0.898, sensitivity 84.6%, and specificity 76.3% for the diagnosis of ANHC and had a higher diagnostic performance (AUROC 0.881, sensitivity 94.1%, and specificity 74.2%) than that of AFP (AUROC 0.705, sensitivity 58.8%, and specificity 73.3%) for early HCC ( 114 ). These findings implicate that sAxl is a diagnostic biomarker with high accuracy for very early HCC and ANHC.…”