The Expression And Clinical Significance Of CD24Protein In Plasma Of HCC Patients

Background and ObjectivesHepatocelluar carcinoma (HCC) is one of the most frequent malignant tumors in the world. It is the fifth most common cause of cancer and the third leading cause of death from cancer worldwide, with more than500000deaths annually. Liver cancer has been shown to have wide variations in the geographic distribution, and there is a remarkable difference in the incidence of genders. The highest incidence rates of HCC are in sub-Saharan Africa and East Asia, with China accounting for over50%of the cases. However, some countries including North and South America, Australia and Northern Europe have a low incidence rate. In most cases, the incidence of HCC is higher in males when compared to females. HCC is the second major cause of death related tumor in China and its incidence and mortality have risen in recent years. Carcinogenesis of HCC has been classified as a complex multistage process and many cellular signaling pathways have been reported to be involved in hepatocarcinogenesis. Major risk factors contributing to HCC include chronic hepatitis B and C virus infections, heavy alcohol intake, aflatoxin-B1exposure and hereditary diseases such as Wilson’s disease and hemochromatosis. These risk factors cause the chronic inflammation of liver through destroying the hepatocyte directly or in directly. Finally, hepatocellular carcinoma happens because of hepatocyte dysplasia and out of control of normal cell cycle.HCC remains silent in early stage and most of patients are diagnosed at an advance stage. The5-year survival rate is less than5percent without treatment. Intrahepatic and extrahepatic recurrence is still frequent in HCC patients, even after curative surgical resection. TACE, Ethanol percutaneous injection, radiofrequency ablation and cryosurgery are widely used treatment for HCC besides the surgery. However, these treatments have a poor prognosis. Therefore, early diagnosis of HCC is the most critical step in the management of HCC. Currently, serum a-fetoprotein (AFP), together with abdominal ultrasonography is the only available tool for the early detection of HCC. However, AFP is not sensitive enough to detect all HCC at the early stage since up to30%-40%of HCC patients have normal AFP levels. The abdominal ultrasonography is highly dependent on the examiner’s experience. Therefore, biomarker with better diagnostic value for HCC is urgently needed.CD24is a small, heavily glycosylated mucin-like cell surface protein comprising27amino acids, and is attached to cell membranes by a GPI anchor. However, increasing studies have found CD24to be overexpressed in a large variety of tumors. In our previous study, we note that CD24is up-regulated in the tissues of HCC patients using gene microarray assay. Studies have demonstrated that CD24, as a ligand for P-selectin, participates in cell proliferation, invasion and tumor metastasis. However, there is no report about the expression of CD24protein in plasma of patients with HCC. Therefore, we investigated the expression of CD24in plasma of patients with HCC and evaluate the diagnostic value of CD24protein as a biomarker for HCC patients.Materials and MethodsNinety consecutive patients with HCC, who were admitted to Henan Provincial People’s Hospital between March2012and July2012, were enrolled in this study. There were53males and37females. Plasma levels of CD24protein and AFP were measured by enzyme linked immunosorbent assay (ELISA) in the plasma of90patients with hepatocellular carcinoma and30healthy controls. The sensitivity and specificity were calculated and the relationship between the expression of CD24and clinical pathological parameters was analyzed. The difference between group means was tested using the Mann-Whitney or Kruskal-Wallis method. Spearman correlation test was used to measure association between CD24and AFP concentration. P values less than0.05(two tailed) was considered to be statistically significant.Results1. Both CD24and AFP levels in the plasma of patients with HCC were significantly higher than those in healthy controls (p<0.05). The median plasma level of CD24was4.43ng/ml in the HCC group, which was higher than2.96ng/ml in healthy controls, and the range of plasma CD24level was wider in patients with HCC compared to normal controls (ng/ml;2.58-14.25vs.1.86-3.54). In addition,there was no correlation between plasma levels of AFP and CD24in90patients with HCC (r=-0.084, p=0.430).2. The best cut-off value for CD24was3.31ng/ml with a sensitivity and specificity of83.3%and93.3%, respectively. The best cut-off value was12.1ng/ml for AFP, which yielded a sensitivity and specificity of75.6%and93.3%. No significant differences were found between the expression of CD24and clinical pathological parameters of HCC patients such as gender, age, hepatitis infection status, tumor size, degree of tumor differentiation and TNM stage (p>0.05).3. The area under the curve was0.955(95%CI:0.900-0.984) for plasma CD24and0.886(95%CI:0.816-0.937) for plasma AFP. There was a significant difference between the two areas (p=0.039).4. In the AFP negative HCC group, the best cut-off value determined by ROC curve was3.42ng/ml, which yielded a sensitivity and specificity of83.3%and96.7%.ConclusionPlasma CD24protein might serve as a novel tumor marker in differentiating HCC patients from normal individuals as well as monitor HCC status in AFP negative HCC patients.