Auxiliary Diagnosis For Primary Hepatic Carcinoma: Feasibility Study On XAGE-1b

XAGE-1 is a new gene discovered by Brinkmann,Vasmatzis and others in 1999 by means of homologous walking,a kind of bioinformatic method.When they searched human expressed sequence tags library near MAGE-PAGE,it was found and located in Xp11.21-Xp11.22.Further study shows that it is typical CT-X antigen expressed in testis and many kinds of tumor restrictively,and it expresses four spliceosomes among which XAGE-1b is main expression product.Clinical research has get detailed expression spectra of XAGE-1b.It is expressed with high percentage in lung cancer,melanoma,prostatic cancer and so on.Furthermore, relationship is gradually being revealed between XAGE-1b expression and clinical factors such as patho-proceeding and tumor hypotype.This study focuses on XAGE-1b expression in healthy individuals and patients with primary hepatic carcinoma(PHC),benign hepatic disease and liver cirrhosis caused by hepatitis,so as to investigate XAGE-1b as a marker of PHC for diagnosis and prognosis judgement.Objective:To value the feasibility of XAGE-1b as auxiliary diagnosis for PHC.Methods:Peripheral blood from 125 patients with PHC,34 patients with benign hepatic disease,23 patients with liver cirrhosis caused by hepatitis and 41 healthy individuals was collected,and XAGE-1b mRNA was detected by quantitative real-time reverse transcription polymerase chain reaction(RT-PCR).Relationship between XAGE-1b mRNA expression and clinical factors such as sex,age,tumor size, pathologic type,clinical stage and AFP was investigated in PHC patients and expression diversity in healthy individuals and different patients was compared.ROC curve was used to analyse the results of XAGE-1b mRNA,AFP,CEA and CA199 to compare their diagnostic value for PHC.Furthermore,XAGE-1b mRNA was detected in tumor tissue and their adjacent non-tumor tissue from 18 PHC patients to compare expression diversity and 100 cases of tumor tissue and their adjacent non-tumor tissue were stained by S-P immunohistochemistry to investigate XAGE-1b protein. Results:XAGE-1b mRNA was detectable in blood from 80.8%of PHC patients. Among them,80.58%of male patients and 81.82%of female patients were detectable (P＞0.05),and detectable rate of different age group(20-39,40-59,60-79 years old group) was 90.0%,77.9%and 82.1%respectively(P＞0.05).Levels of XAGE-1b mRNA in blood were not obviously different between big hepatic carcinoma(tumor diameter＞5cm) and small hepatic carcinoma(tumor diameter≤5cm),hepatocellular carcinoma and cholangiocellular carcinoma,clinical stageⅠ,Ⅱ,ⅢandⅣ,patients with AFP positive and the AFP negative(P＞0.05),but the positive rate of XAGE-1b mRNA in blood from patients with hepatocellular carcinoma was obviously higher than that of AFP(P＜0.01).Especially,82.35%of PHC patients with AFP negative was found XAGE-1b mRNA in blood and there was no dependablity between XAGE-1b mRNA and AFP(95%confidence interval from -0.21 to 0.10.Levels of XAGE-1b mRNA in blood from PHC patients were higher than from other patients and healthy individuals(P＜0.01),and from liver cirrhosis patients were higher than from patients with benign hepatic disease and healthy individuals(P＜0.05),yet from patients with benign hepatic disease and healthy individuals were similar(P＞0.05).ROC curve judged the diagnostic value of XAGE-1b mRNA,AFP,CEA and CA199 for PHC,the AUC was 0.879,0.759,0.648 and 0.511 respectively.XAGE-1b mRNA was more accuracy than others and AFP was the second,but CEA and Ca199 had little diagnostic value.Levels of XAGE-1b mRNA in tumor tissue from 18 PHC patients were higher than in their adjacent non-tumor tissue and peripheral blood(P＜0.01),and in adjacent non-tumor tissue were higher than in peripheral blood(P＜0.01).Protein of XAGE-1b was detected in tumor tissue and adjacent non-tumor tissue from 100 PHC patients by immunohistochemistry,and it was more increased in distant metastasis than in primary tumor,which was observed in one case,but other cases were negative.Conclusion:The expression of XAGE-1b mRNA in blood from PHC patients doesn't associate with sex,age,tumor size,pathological category,clinical stage and AFP.Through XAGE-1b mRNA,PHC patients can be discriminated from healthy individuals and patients with benign hepatic disease or liver cirrhosis caused by hepatitis.It can predict tumor cell micrometastasis in blood and contribute to diagnose PHC as a tumor marker,especially has diagnostic value for hepatocellular carcinoma with AFP negative.It may have considerable significance for prognostic judgment and treatment selection for PHC.