| BackgroundHepatic cirrhosis and hepatocellular carcinoma (HCC) caused by chronic infection with hepatitis B virus (HBV) has increasingly caused great social and medical burdens for China. The long latency between infection and disease onset in this high-risk population provides an opportunity for early detection before the onset of advanced disease. Development of more sensitive and specific serum markers for the early detection of HCC in the at-risk population and early detection of postoperative recurrence may improve survival of patients with this deadly tumor. The routine used biomarker AFP indicates a sensitivity of 39-65%, averagely about 50%. As a surveillance tool, both the sensitivity and specificity of AFP are far from satisfaction. Resulted from which, some patients couldn't be detected at the early stage of HCC and then treated promptly.Recent proteomics techniques have developed and suggested a group of novel HCC serum tumor markers, which could become the hope of HCC early detection. Among them, Golgi Protein 73 (GP73) is one of the most prominent and promising serum markers, the value of which has gradually been proven in various studies. Our previous large multicenter clinical study regarding GP73 with over 4,000 subjects and fully comparisons has shown the confirmed and steady advantages of serum GP73 (sGP73) in diagnose of HCC over AFP.However, the majority of relevant researches on GP73, including our large cohort study, have been focused on the feasibility of sGP73 as the value of tumor biomarker. Few studies that have investigated GP73 expression pattern in liver tissues, and were mainly confined to immunohistochemistry, and lack of whole scale investigation. To the best of our knowledge, there were no study to research GP73 expression at both protein and mRNA levels in HCC tumors, paracarcinomatous liver (PCL) tissues and normal liver (NL) tissues, and the correlation between its expression pattern and patients' clinicopathologic parameters. GP73's biological role and molecular function in hepatocarcinogenesis haven't been clarified. AimThis study aimed to investigate GP73 expression pattern in HCC tissue, the corresponding patients'sGP73 and its correlation with the clinicopathologic parameters and further the potential relationship between GP73 and the growth, invasion, recurrence and metastasis of HCC. The result illustrated GP73'biological role in hepatocarcinogenesis at both molecular and genetic levels, providing novel pathway of tumor growth restraining and HCC targeted treatment.MethodsWe examined GP73 expression in HCC tumors and paracarcinomatous liver tissues (PCLT) from 36 HCC patients and that in normal liver (NL) tissues from 14 hepatic hemangioma patients, using Western blot analysis and Quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR), respectively. Further, we try to observe the correlation between GP73 expression level in HCC tumors and patients' clinicopathologic parameters such as sex, age, liver function, tumor size, tumor differentiation, tumor nodules, vein invasion, AFP levels, and recurrent status, including patients'prognosis.ResultsCoincide with that from our previous large cohort study, the medium sGP73 value in the HCC patients was 10.2 (4.8-18.4) relative units (RU), which was significantly elevated compared with that in control group [1.1 (0.7-1.4) RU, P<0.001]. The median protein level of GP73 in HCC tumor was 11.0 RU, with a range from 7.5-15.5 RU, which was significantly higher than that in PCL tissues [3.9 (2.5-6.6) RU, P<0.001], and NL tissues [1.5 (1.1-2.4) RU, P<0.001]. Consistently with these protein expressions, mRNA level of GP73 in HCC tissues [3.3 (1.6-5.2) RU] was also significantly higher than that in PCL tissues [1.8 (1.0-2.9) RU, P<0.01] and NL tissues [1.1 (0.7-1.4) RU, P<0.001]. There was, however, no significant positive correlation between the increased levels of GP73 protein and mRNA by spearman correlation coefficient analysis (r=0.225; P=0.188). That was also true between tissue GP73 protein and serum GP73 in the corresponding HCC patients (r=0.141; P=0.413).Tissue protein expressions of GP73 in the HCC patients with tumor size> 3cm were markedly higher than those with tumor size≤3cm [12.3 (9.3-16.5) RU vs.7.6 (5.0-12.4) RU, P<0.05]. GP73 protein levels in the HCC patients with venous invasion were significantly higher when compared with those without venous invasion [16.2 (11.2-21.5) RU vs.9.9 (6.8-13.4) RU, P<0.05]. Over expressions of GP73 protein were shown in the tumors with moderate differentiation compared with high differentiation [13.5 (10.0-18.5) RU vs.9.7 (7.6-12.5) RU, |
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