| Research background and objectivePrimary liver cancer(PHC)is one of the most common malignant tumors in the world.Its morbidity and mortality rank fifth and fourth respectively,and it is one of the malignant tumors with high mortality.Nearly half of new cases and deaths occur in China.Hepatocellular carcinoma(HCC)is the most common type of primary liver cancer,and the treatment is mainly surgical resection.Although comprehensive treatments such as radiochemotherapy and molecular targeted therapy have made great progress in recent years,the 5-year survival rate of each clinical stage is still very low.In both European and American countries or in China,HCC is still considered to be a malignant tumor with a poor prognosis,which is related to its high degree of malignancy and early infiltration and metastasis.The early symptoms of the patient are not easy to be noticed,and most of the patients have progressed to the middle and late stages when they are diagnosed,so the opportunity for early detection and treatment is lost.Therefore,finding an effective and simple screening marker to make it a screening indicator for high-risk groups can achieve early detection,early diagnosis and early treatment,and can assist in the differential diagnosis,histological classification,and prognosis judgment of HCC.This screening index can provide a basis for the rational formulation of clinical diagnosis and treatment plans,so as to achieve the purpose of improving the prognosis of HCC patients.With the rapid development and the widespread clinical application of immunohistochemistry(IHC)in pathological diagnosis,various immunohistochemical markers have emerged widely,which has become more and more helpful for the accurate diagnosis and treatment of malignant tumors.At present,GPC-3 is one of the most reliable tumor markers for differential diagnosis between HCC and benign liver lesions,intrahepatic cholangiocarcinoma,metastatic cancer and other non-HCC liver diseases.Ki-67 is another biomarker that exists only in proliferating cells,so its expression can indirectly reflect the number of proliferating cells,and can be used to predict the malignant degree of the tumor.This study intends to explore the relationship between tumor pathological differentiation and GPC-3 and Ki-67 indexes in HCC tissues,as well as the correlation between GPC-3 and Ki-67 index in order to more fully understand the proliferative activity of liver cancer.These will help to further judge the prognosis of HCC patients and provide a basis for the diagnosis and treatment plan of HCC.MethodsThis study collected a total of 404 patients with primary hepatocellular carcinoma confirmed by surgical pathology or biopsy pathology in Shandong Provincial Hospital from January 2014 to July 2018,inclusion criteria:postoperative pathologically confirmed patients with hepatocellular carcinoma who did not receive any anti-tumor treatment prior to surgery or biopsy.Clinical data of these patients,such as aspartate aminotransferase,alanine aminotransferase,AFP,hepatitis B,etc.were collected within ten days before surgery or biopsy.If there are multiple intrahepatic tumors,take the largest lesion as the research object.According to the Edmondson-Steiner pathological grading method for liver cancer,the degree of differentiation of tumor tissue is divided into four levels:high differentiation,medium differentiation,low differentiation,and undifferentiated.When the tumor tissue of the same patient shows two or more different degrees of pathological differentiation,the lower differentiation prevails.For example,high-medium differentiation is recorded as medium differentiation,and medium-low differentiation is recorded as lowdifferentiation.SPSS 18.0 statistical software was used for data analysis.Measurement data conforming to the normal distribution were compared using t test.χ2 test was used to analyze the difference in expression of GPC-3 or Ki-67 between different clinical feature groups.The correlation analysis between Ki-67 and serum AFP level or the maximum diameter of the lesion was performed by Spearman correlation test.Correlation analysis was used to correlate Ki-67 expression with each pathological grade.P<0.05 was considered as statistically different.ResultsA total of 404 patients met the inclusion criteria,of which 308 were positive for GPC-3 expression and 96 were negative.The positive rate of GPC-3 in HCC was 76.2%.The positive rate of GPC-3 was the lowest in well-differentiated tumors,while it was significantly increased in low-differentiated and undifferentiated hepatocellular carcinoma.The positive rate of GPC-3 was statistically different between clinicopathological characteristics such as different age of onset,degree of pathological differentiation,plasma AFP level(P<0.05).The Ki-67 index is(23.9±18)%(the lowest value is 1%and the highest value is 90%).There is a significant correlation between the level of Ki-67 index and the degree of differentiation of tumor tissue,the maximum diameter of the lesion,and the level of AFP(P<0.05).There was no significant correlation between Ki-67 index and clinicopathological features such as gender,age,lesion location,hepatitis B infection pattern,AST,ALT,total bilirubin,albumin,etc.(P>0.05).Correlation analysis showed that the degree of pathological differentiation of hepatocellular carcinoma had a significant correlation with Ki-67 index.The lower the degree of tumor differentiation,the higher the Ki-67 index.The t-test was used to analyze the distribution of Ki-67 index in the GPC-3 positive group and the negative group.The Ki-67 index of the GPC-3 positive group was(25.96 ± 17.65)%,and the Ki-67 of the negative group was(17.46±17.70)%.There is a significant statistical difference between the two groups(P<0.01),that is,compared with HCC patients with negative GPC-3 expression,the tumor proliferation index Ki-67 is higher in those with positive GPC-3 expression.Conclusion1.The expression of GPC-3 in hepatocellular carcinoma is related to the degree of tumor pathological differentiation.The GPC-3 positive rate of well-differentiated hepatocellular carcinoma is significantly lower than that in poorly differentiated patients.2.The Ki-67 index of patients with differently differentiated hepatocellular carcinoma is significantly different and has statistical significance.The Ki-67 index is negatively correlated with the degree of pathological differentiation of hepatocellular carcinoma.3.The expression of GPC-3 is positively correlated with Ki-67 index,that is,the expression of Ki-67 is higher in GPC-3 positive patients.Since GPC-3 is only highly expressed in hepatocellular carcinoma tissues,targeted therapy for GPC-3 will likely become a research hotspot. |
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