Expression Of MALAT1 In Hepatocellular Carcioma And Its Clinical Significance

Background: Hepatocellular carcinoma has the characteristics of high incidence, high mortality and poor prognosis as the primary malignant tumor of the liver. Most of early stage HCC patients could benefit from surgery, but postoperative recurrence is a bottleneck which restricts the long-term efficacy of HCC patients. Therefore, searching for an effective biological index to predict the recurrence and metastasis of patients appears extremely important. MALAT1,one of the lncRNAs, widely expresse in a variety of normal tissues, and has tissue specificity. However, MALAT1 was found abnormally expression in a variety of malignant tumor tissues and plasma. The level expression of MALAT1 is closely related to tumorigeness,development, metastasis and prognosis. However, the study of MALAT1 is less coverage especially on clinical parameters and prognosis of HCC patients.Objective: To explore the expression of MALAT1 in hepatocellular carcinoma tissue, the relationship between the expression of MALAT1 and clinical pathological features of HCC patients . Furthermore, analysis of the role of MALAT1 in the recurrence of hepatocellular carcinoma after radical operation, which may help us evaluate the prognosis of patients with liver cancer biomarkers providing clinical basis.Methods: In the present study, trizol method was used to extract total RNA from the tissues, and reverse transcription of RNA. We evaluated the expression of MALAT 1 by quantitative real-time PCR in 73 HCC cases who received radical resection of liver cancer with complete follow up data, and the clinicopathological significance of the MALAT 1 expression was evaluated.Results: 1. MALAT1 amplification plot and melt curve: MALAT1 amplification plot showed the type of smooth "S" with significant period of amplification and plateau. MALAT 1 dissolution curve showed one single peak,suggesting that the MALAT 1 was good purity, and the solution temperature was 80.96℃. 2. Real-time fluorescence quantitative PCR determination: In 73 cases of HCC, the expression of MALAT 1mRNA was significantly lower than that of the corresponding noncancerous tissues. The median value of 3.15 (1.46, 6.63)vs 17.45 (8.77, 22.15). The difference between the two groups displayed statistical significance (Z=2.547,P<0.001).3. The relationship between expression of MALAT 1mRNA and clinical case characteristics in HCC: The expression of MALAT 1 was related to the size of HCC tumor, preoperative AFP,and cirrhosis. MALAT 1mRNA relative expression was significantly higher in maximum tumor diameter > 5cm group compared with the other group, the difference was statistical significance (Z=-2.611, P = 0.009). MALAT1mRNA expression in high level of AFP was significantly higher than the low level of AFP, the difference between the groups was statistically significant (Z=6.201,P=0.045). In combined with liver cirrhosis and HCC tissues and MALAT1mRNA expression levels for 3.91 (1.9443, 9.6541, significantly higher than non cirrhotic HCC the expression level of 2.08 (1.2854,3.3997), the difference has statistical significance (Z=-2.351, P = 0.019).The difference of MALAT1 expression level had no statistical significance in different age, gender,ethnicity, smoking history, family history, history of hepatitis, different levels of ALT, AST, TB, tumor numbers,envelope,vascular invasion,grading,TNM and BCLC (P>0.05).4. The relationship between MALAT1mRNA expression and the prognosis of HCC: In 73 cases of HCC, 44 cases recurred after operation and 29 cases did not. The expression level of MALAT1mRNA in 12～18m group was significantly higher than other periods after HCC radical operation, and the difference was statistically significant (Z=9.437,P=0. 028) . MALAT1mRNA expression level was the lowest after radical postoperative in 6 months relapse.MALAT1mRNA expression level was the highest after the radical postoperative in 12～18m recurrence,which indicated that the expression of MALAT1mRNA was related to the recurrence time of HCC after radical operation. The role of MALAT1 in the mechanism of recurrence and metastasis of primary hepatocellular carcinoma is worthy of further study.Conclusion: 1 .The expression of MALAT1 mRNA in adjacent tissues was significantly higher than that in the cancer tissues.2. The expression level of MALAT1 was significantly increased in the preoperative APF > 400 g/L group.3. The expression level of MALAT1 was significantly higher in the tumor diameter >5cm group compared with the other group.4. The up-expression of MALAT1 in HCC tissues suggests that 12～18m is prone to recurrence after surgery, which could be used as an indicator to predict the risk of recurrence after radical surgery for HCC patients.