Expression Of TKTL1,TUM2-PK And PFKFB3 In Hepatocellular Carcinoma And Its Clinical Significance

Objective To approach the expression of transketolase genes (TKT, TKTL1 and TKTL2) in human hepatocellular carcinoma (HCC) tissues, and to explore the association between the expression of transketolase genes mRNA and clinicopathological features in HCC. meanwhile, TUM2-PK and PFKFB3, the key enzyme of the upper reaches of transketolase reaction,were detected and these correlation with transketolase were study for discussing the regulation and implications factor of transketolase metabolic pathways.Methods Transketolase activity were assayed in 42 cases HCC and para-cancerous tissues, reverse transcription-polymerase chain reaction (RT-PCR)was used to detect the mRNA of transketolase genes (TKT, TKTL1 and TKTL2),TUM2-PK and PFKFB3.Reviewed the clinical and follow-up data and studied the clinicopathological implications of these genes.Kaplan-Meier test was used for univariate survival analysis, Cox's proportional hazards regression model was used for multivariate survival analysis.Results The transketolase activity in HCC and para-cancerous tissues were 20.16±1.67 and 2.62±0.88. transketolase activity in HCC were significantly higher than para-cancerous tissues(P<0.01). TKT, TKTL1, TKTL2 mRNA expression were 78.57% (33/42), 90.48% (38/42), 66.67% (28/42) in HCC, and 92.86% (39/42), 40.48% (17/42), 47.62% (20/42) in para-cancerous tissues respectively. the mRNA expression of TKTL1 in HCC was significantly higher than para-cancerous tissues(P<0.01), while there were no different in TKT and TKTL2 (P>0.05). The mRNA expression of TKTL1 was significantly higher than TKT and TKTL2 in HCC(P<0.05). The mRNA expression index(RI) of TKT,TKTL1,TKTL2 were 0.53±0.42, 0.73±0.47,0.72±0.53 in HCC,and 0.39±0.33,0.33±0.28,0.40±0.28 in para- cancerous tissues respectively. The RI of TKTL1 and TKTL2 mRNA in HCC was significantly higher than para-cancerous tissues(P<0.05), while there were no different in TKT (P>0.05). The expression of TKTL1 were related to tumor differentiation degree , cancer embolus in vein, intrahepatic metastasis and 5-year survival rate(P<0.05), but not to gender, age, tumor size, lymphatic metastasis and the level of AFP(P>0.05). There were no clinicopathological features related to TKTL2 except tumor differentiation degree(P<0.05). TUM2-PK and PFKFB3 mRNA expression were 83.33% (35/42), 73.81% (31/42) in HCC, and 57.14% (24/42), 52.38% (22/42) in para-cancerous tissues respectively.The RI of TUM2-PK and PFKFB3 were 0.7230±0.6744, 1.0751±0.1712 in HCC, and 0.2594±0.2835,0.8769±0.4511 in para-cancerous tissues respectively. Both the mRNA expression and RI of TUM2-PK and PFKFB3 in HCC were significantly higher than para-cancerous tissues(P<0.05). The expression of TUM2-PK were related to the degree of differentiation (P<0.05). The expression of PFKFB3 were related to degree of tumor differentiation, intrahepatic metastasis and 5-year survival rate (P<0.05). The mRNA expression intensity of TUM2-PK was positively correlated with TKTL1 (R=0.307,P<0.05).The mRNA expression intensity of PFKFB3 was positively correlated with TKTL1 too(R=0.329, P<0.05). While there were no correlation between TUM2-PK,PFKFB3 and TKTL2 (P>0.05). Clinicopathological parameters (Gender, age, tumor size, differentiation degree, lymphatic metastasis and cancer embolus in vein) and genes(TKTL1, TKTL2, TUM2-PK and PFKFB3) were bringed into the COX proportional hazards regression model.The results showed that TKTL1 was an independent risk factor of the prognosis of patients with HCC (RR=3.604, P<0.05).Conclusion This study show that transketolase may play an important role in carcinogenesis and development of HCC. The main reason of that is the high expression of TKTL1. TUM2-PK, PFKFB3 and TKTL1 may play cooperation role in carcinogenesis, development and metastasis of HCC. The high expression of TUM2-PK indicates poorly differentiated of HCC and the high expression of TKTL1 or PFKFB3 indicates poorly differentiated ,easy to transfer and poor prognosis of patients with HCC. They may be used as biological indicators of the degree of malignancy. TKTL1 may be an important prognostic marker for the clinical outcome.