The Value Of Hexokinase-2Expressions In Evaluating Hepatocellular Carcinoma Prognosis

Objective: Hepatocellular Carcinoma HCC is the malignancy with relatively highincidence and mortality rates. As the development of treatment methods, the overallglobal survival rate of HCC has been increased, however, still in a relatively low level.There are many factors that can affect HCC patients’survival rates. Currently,researches on unusual tumor tissue glycolytic process (Warburg effect) has discoveredthat Hexokinase2(HK-II, a significant regulator in malignant tissues’energy metabolicprocess that has close relationship with cancerous cells’growth and aggresivity) is thefirst significant enzyme in catalytic glycolysis. This study was aimed to examine theprotein expression of HK2in HCC and the correlation between major clinicalpathological factors and prognosis of HCC,and to provide new clinical research basis onnew HCC treatments.Methods: Our samples were120HCC patients who had their first tylectomys fromJanuary2008to May2013in First Affiliated Hospital, Da Lian Medical University.120patients’paraffin-embedded cancerous tissues,30paraffin-embedded adjacentnoncancerous tissues, and every patient’s clinical information were collected. At thesame time, patients’life spans were inquired from Diseases Control Center and hospitalrecords. With the assistance of pathology department instructors, immunohistochemicalmethod was employed in detecting the expression of HK-II in these cancerous andadjacent noncancerous tissue samples, and then the relationship between the detectingresults and clinical features and patients’prognosis were analyzed. χ2was used toexamine and analyze the numerical data. Kaplan-Meier method was used in evaluatingsurvival rate. Log-rank sequence checking test and Cox proportional hazards regression model was used in making mono-factorial and muti-factorial analysis respectively.Results:1. HCC patients’clinical characteristics distributionThe majority of the120samples were male, with male female ratio3.62:1, age from23to83, average age55.9±4.95, median52.5. Age distribution (years):<60had80samples (66.67%),≥60had40samples(33.33%). HBV infection history distribution:106samples (88.33%) with HBV infection history and14samples (11.67%) with noHBV infection history. TBIL (μm/L) distribution:97samples (80.83%)<24,20samples (16.67%) from24to51, and3samples (2.5%)>51.ALB distribution (g/L):97samples(80.83%)>35,21samples (17.50%) from28to35, and2samples (1.67%)<28.In Child-Pugh classification distribution, there were103samples (85.83%),14samples(11.67%), and3samples (2.5%) inA, B, and C stages respectively.AFP(ug/L)distribution:30(25.00%)samples≥400and90samples (75%)<400. Tumor size(cm)distribution:37samples (30.83%)≥5,83samples (69.17%)<5. Clinical TNM stagedistribution: there were46samples (38.34%),34samples (28.33%),36samples(30.00%), and4samples (3.33%), in stage I, II, III, and IV respectively. BLAC stagedistribution: majority of the samples were inAstage with98samples (81.67%). Thereare9samples (7.50%),10samples (8.33%),3samples (2.50%), in stage B, C, and Drespectively.2. The expression of HK-II protein in HCCThe positive express rate of HK-II protein in HCC was57.50%; the positive expressrate of30samples’paraneoplastic tissues was0%. There were prominent differencesbetween hepatoma carcinoma tissues and paraneoplastic tissues (χ2=17.633，p<0.05).3. The expression of HK-II protein’s relationship with clinical characteristicsThere was no prominent relationship between HK-II protein expression and patients’ages, genders, tumor sizes, HBV infection history, BLACK staging, and Child-Pughclassifications(p>0.05). However, there were correlations between such expressions andAFP,ALB, and TNM classifications(p<0.05). The expression rate of HK-II protein ofHCC tissues in stage I, II, III and IV were27.54%,34.78%, and37.68%respectively, which show remarkable differences(χ2=5.124, p=0.0236). Meanwhile, there was a directrelationship between HK-II protein expression and TNM classification(γ=0.208,p=0.0224).4. Monofactorial analysis between clinical characteristics and prognosis effectsThe results of Kaplan-Meier method monofacorial analysis have indicated that therewere significant differences between the expressions of HK-II and HCC patients’prognosis(p<0.05).5. Mutifactorial analysis between clinical characteristics and prognosis effectsThe hierarchical information above has been substituted into Cox proportionalhazards regression model and then Forward mehtod has been used to make muti-factorial analysis. The results indicated that HK-II protein expression, gender and TNMstage have statistical significances(p<0.05). They were independent prognostic factorsthat could affect HCC patients’prognosis.However, age, HBV infection history,ALBdata hierarchy, TBIL data hierarchy, Child-Pugh category,AFP data hierarchy, tumorsizes, and BLAC staging have no statistical significance towards HCC patients’prognosis(p>0.05). They were not independent factors that could affect HCC patients’prognosis.Conclusion:1. Examining HK-II protein expression in HCC can help in determining malignancy andillness progression.2. HK-II’s positive expression is an independent factor that can affect patients’prognosis after tylectomys.