Expression And Clinical Significance Of NPRL2 And Survivin In Hepatocellular Carcinoma

Background and Aim:Hepatocellulur carcinoma (HCC) is one of the most common malignant tumors in China. With the rapid development of medical technology, the early diagnosis, treantment, and prognosis of HCC have improved significantly, but unfortunately, its mortality rate is still high[1]. Gene mutation plays an important role in the development and progression of HCC, which results in activation of oncogenes and inactivation of anti-oncogenes[2] NPRL2 (nitrogen permease regulator-like 2), a candidate tumour suppressor gene found in lung cancer, expresses in many normal tissues including liver, lung and kidney, while its down-regulation is discovered in many malignant tumors like colorectal cancer and lung cancer[3,4] Nevertheless, there are few researches about NPRL2 in HCC. Survivin, which is one of inhibitor of apoptosis gene family, participates in the control of cell division, apoptosis and tumor angiogenesis. The upregulation of survivin is related to almost all cancers such as lung cancer and breast cancer[5]. The PI3K/PDK1/AKT signaling path refers to multiple functions, for instance, cellular homeostasis and proliferation, whose dysregulation may lead to cancers[6]. There have been researches that both NPRL2 and survivin are involved in the PI3K/PDK1/AKT pathway but with completely opposite effects. However, the relationship between NPRL2 and survivin has not been discussed yet. With using the methods of RT-PCR and immunohistochemistry, we studied the expression of NPRL2 and survivin in HCC from RNA to protein level, their relationships with clinical pathologic significance and the correlation between the two genes, to direct their clinical practice.Meterials and Methods:During the period from May 2013 to June 2014,45 cases of HCC tissues, paracancerous liver tissues and 15 cases of normal liver tissues were obtained from the operative specimens of Shandong Provincial Hosipital. Some tissue samples were used to extract RNA and others were embeded in paraffin. Immunohistochemistry and RT-PCR methods were used to measure the expression levels of NPRL2 and survivin. Meanwhile, we collected the clinical pathologic significance of all the HCC patients to analysis the connection between the two genes and the clinical indexes.Results:1.RT-PCR results showed that there were lower NPRL2 mRNA expression in HCC tissues than in paracancerous liver tissues and normal liver tissues, with their relative expression levels were 0.36±0.06,0.52±0.07,0.55±0.07, respectively. By immunohistochemistry, NPRL2 protein was expressed at significantly higher rate in normal liver tissues and paracancerous liver tissues compared with HCC tissues (P<0.01). Their positive rates were 86.67%(13/15),93.33%(42/45),33.33%(15/45), respectively. NPRL2 mRNA and protein were detected to be expressed equally in normal liver tissues and paracancerous liver tissues (P>0.05).2.The expression levels of survivin mRNA in HCC tissues (1.47±0.08) increased distinctly, compared with paracancerous liver tissues (0.78±0.05) and normal liver tissues (0.76±0.06) (P<0.01). The positive expression rates of survivin protein were apparently higher in HCC tissues than in paracancerous liver tissues and normal liver tissues (P<0.01). Their positive rates were 64.44%(29/45),8.89%(4/45),20%(3/15), respectively. However, survivin mRNA and protein were discovered to be expressed equally in paracancerous liver tissues and normal liver tissues (P>0.05).3.Analysis of NPRL2 and survivin immunohistochemical staining results showed that no distinct associations were observed with clinicopathological parameters including gender, age, tumor size, portal venous tumor thrombus, HBsAg, HBeAg, HBV-DNA (P>0.05), whereas both were related to lymph metastasis and TNM stage (P<0.05). Furthermore, survivin protein was correlated with serum AFP concentration (P<0.05).4.By spearman relative analysis, there was obvious negative correlation between NPRL2 mRNA and survivin mRNA in hepatocellular carcinoma (r=-0.45, P<0.01)Conclusion:Our results showed that anti-oncogene NPRL2 and oncogene survivin had negative regression in hepatocellular carcinoma. The two genes may provide novel theoretical basis and tumor therapy for HCC, due to their important roles in the occurence and development of HCC.