The Value Of IGF2BP1 And IGF2BP3 In The Diagnosis Of Hepatocellular Carcinoma

Objective: To investigate the applicative value of insulin-like growth factor II mRNA binding protein 1(IGF2BP1)and insulin-like growth factor II mRNA binding protein 3(IGF2BP3)in the diagnosis of hepatocellular carcinoma(HCC).To explore the diagnostic difference in HCC between them alone or combination and together with the detection of phosphatidylinositol proteoglycan-3(GPC3),and also to discuss the diagnostic difference in HCC between joint detection of the three index above and cooperative detection of GS,HSP70 and GPC3.Methods:The expression of IGF2BP1,IGF2BP3 was detected immunohistochemistrically in 163 cases HCC surgical specimens and corresponding paracancerous nontumor liver tissues made by tissue chip technology.The relationship between the expressive levels of IGF2BP1 and IGF2BP3 in HCC and the clinicopathological characters were also studied.The sensitivity and specificity of IGF2BP1 and IGF2BP3 alone or combined with GPC3 in detecting HCC were analyzed.Meanwhile,immunohistochemistry was also used to detect the expression of IGF2BP1 and IGF2BP3 in 53 cases HCC biopsy specimens,4 cases High Grade Dysplastic Nodules(HGDN)specimens and 6 cases Low Grade Dysplastic Nodules(LGDN)specimens respectively.These results were compared with those of microarray detection.At the same time,tissue microarray technique was used to detect the expression of HSP70 and GS in the same 163 cases HCC and corresponding paracancerous non-tumor liver tissues by immunohistochemical method.The sensitivity and specificity were analyzed between the joint detection of IGF2BP1,IGF2BP3,GPC3 and combined detection of HSP70,GS,GPC3.Results : IGF2BP1 and IGF2BP3 were highly expressed in tissue microarrays of 163 cases HCC surgical specimens,and were not expressed in corresponding adjacent nontumor liver tissues,high and low grade dysplastic nodules.The difference was obviously(P<0.05).The expressive level of IGF2BP1 in HCC was related to serum AFP level and cirrhosis(P<0.05).The expressive level of IGF2BP3 in HCC was also related with serum AFP level and vascular invasion(P<0.05).The expressive level of IGF2BP3 and GPC3 in HCC were related to the degree of HCC differentiation,and the expression of poor differentiation was higher(P<0.05).The sensitivity of IGF2BP1 in the tissue microarray was 52.8%,the specificity was 100%;the sensitivity of IGF2BP3 was 46.1%,the specificity was 100%;the sensitivity of IGF2BP1 combined with IGF2BP3 was 71.2%,the specificity was 100%;the sensitivity of IGF2BP1 combined with GPC3 was 88.96%,the specificity was 97.56%;the sensitivity of IGF2BP3 combined with GPC3 was 85.89%,the specificity was 98.16%;the specificity of three above combination was 91.4%,the specificity was 96.9%,The combined detection improved HCC diagnostic sensitivity significantly(P<0.05).In HCC biopsy specimens,the sensitivity of IGF2BP1,IGF2BP3 and GPC3 were 58.5%,45.3% and 58.5% respectively.The sensitivity of IGF2BP1 combined with IGF2BP3 was 71.7%,IGF2BP1 combined with GPC3 was 84.9%,IGF2BP3 combined with GPC3 was 75.5%,and the three combined detection was 92.5%.The expressive differences of IGF2BP1,IGF2BP3 in HCC punctured specimens and surgical specimens were not statistically significant(P>0.05).The sensitivity of combined HSP70,GS and GCP3 detection in HCC was 98.2%,and the specificity was 83.4%.The combined detections of IGF2BP1,IGF2BP2 and GPC3 were not significant than those of joint detections of HSP70,GS and GPC3(P>0.05).The specificity of the latter was slightly higher.Conclusion: IGF2BP1 and IGF2BP3 were highly expressed in HCC,and not expressed in corresponding adjacent non-tumor liver tissues,high and low grade dysplastic nodules,and their expressive levels in HCC were related to serum AFP levels,which suggests that IGF2BP1 IGF2BP3 may be related to the occurrence of HCC.They may provide some reference value for pathological diagnosis of benign and malignant liver diseases.The expressive level of IGF2BP1 in HCC was related to cirrhosis,and the expressive level of IGF2BP3 in HCC was also related to differentiation and vascular invasion.IGF2BP1 and IGF2BP3 are not sensitive to the diagnosis of HCC alone,but can significantly improve detective sensitivity combined with GPC3;No difference is observed between the expression of IGF2BP1 and IGF2BP3 in the tissue microarray and biopsy specimens.It implies that the biopsy specimens may use to take pathological diagnosis.There is no difference between HSP70,GS,GPC3 combined detection and those of IGF2BP1,IGF2BP3,GPC3.The combination of IGF2BP1,IGF2BP3 and GPC3 has slight lower sensitivity and higher specificity.It suggestes that different screening schemes may be selected according to different diagnostic needs.