| Objective:①To study the distribution and the diagnosis value of sMICA in infectious diseases and malignant tumor in Han population in Hunan Province.②To study MICA gene polymorphism and the expression levels of sMICA in HBsAg positive cirrhosis, HBsAg positive and other types of liver cancer.Methods:①ELISA was used to detect the serum levels of sMICA in495patients with malignant tumor,546patients with infectious diseases and141normal controls. The correlation between the serum levels sMICA and different deseases was then analyzed.②PCR-STR microsatellite genotyping was used to characterize the polymorphism of MICA in exon5in101patients with HBsAg positive Cirrhosis and141normal controls, and the relevance index between them was calculated.③PCR-STR microsatellite genotyping was used to detect the polymorphism of MICA in Exon5in141cases of liver cancer and141cases of normal controls, and the relevance index between them was calculated.④PCR-STR microsatellite genotyping was used to detect the polymorphism of MICA in Exon5in101cases of HBsAg positive Cirrhosis and116cases of HBsAg positive liver cancer, and the relevance index between them was calculated. Results:①The serum levels of sMICA of patients by bacteria, tuberculosis, syphilis helicoid, HBV, HCV, EBV, HSV, CMV and COX-V infection could increase. From high to low levels of s-MICA were found in patients with gram-positive aureus(542.3±382.9pg/ml), tubercle bacillus (493.9±256.4pg/ml), enterobacter (492.2±295.9pg/ml), HCV (474.9±123.1pg/ml) and HBV (472.4±103.6pg/ml), respectively. The lowest serum levels of s-MICA (251.2±256.3pg/ml) was found in the patients with EBV, HSV, CMV, or COX-V infections. The serum levels of sMICA could be employed to diagnose diseases infected by gram-negative bacilli (AUC=0.742), tubercle bacili (AUC=0.766), hepatitis bvirus (AUC=0.712), syphilis helicoid (AUC=0.707) and hepatitis cvirus (AUC=0.701).②Among the patients with different types of malignant cancers, patients with liver cancer had the highest levels of sMICA (743.4±110.8pg/ml), and patients with gastric cancer had the second highest levels of sMICA (264.4±524.8pg/ml).In comparision, the serum levels of sMICA were relatively lower in patients with female reproductive system tumors and malignant lymphoma (140.9±137.6pg/ml and162.5±116.1pg/ml). The serum levels of sMICA in liver cancer patients exhibited diagnostic value (AUC=0.843).③5allelic genes and their frequencies were identified in MICA Exon5and showed as below:MICA*A4(10.9%), MICA*A5(37.1%), MICA*A5.1(34.1%), MICA*A6(7.4%), MICA*A9(10.4%). Only MICA*A5.1is positively associated with liver cirrhosis onset.④The serum levels of soluble MICA in the MICA*A5.1homozygous patients were the highest, up to596.6±163.3pg/ml. While the serum levels of soluble MICA in MICA*5.1heterozygous patients and patients without MICA*A5.1polymorphism were (549.1±101.1) pg/ml and (364.4±132.7)pg/ml, respectively.(5)5allelic genes were also identified in MICA Exon5in141patients with liver cancer in Hunan province. The alleles and their frequencies were MICA*A4(11.7%), MICA*A5(34.0%), MICA*A5.1(35.1%), MICA*A6(8.2%) and MICA*A9(11.0%), respectively. MICA*A5.1is positively associated with liver cancer incidence.⑥The soluble MICA levels appeared to be the highest in the serum of MICA*A5.1homozygous patients with liver cancer, up to (1284±295) pg/ml, compared to (981.4±252.5) pg/ml in MICA*A5.1heterozygote patients and (467.6±48.5)pg/ml in patients without MICA*A5.1.⑦MICA gene polymorphism was uniformly distributed in patients with HbsAg positive Cirrhosis and patients with HbsAg positive HCC. The sMICA level in the blood of MICA*A5.1homozygous patients with HbsAg positive Cirrhosis was (596.6±163.3)pg/ml, and was (983.3±266.6) pg/ml in those patients with HbsAg positive HCC, where was (549.1±101.1)pg/ml in the blood of A5.1heterozygote patients with HbsAg positive Cirrhosis and (813.6±212.3)pg/ml in the blood of A5.1heterozygote patients with HbsAg positive HCC. It appeared the lowest in the patients without A5.1genes, respectively529.1±186.2pg/ml in those with HbsAg positive Cirrhosis and (364.4±132.7)pg/ml in those with HbsAg positive HCC.Conclusion:①Infection of liver cancer, HBV, HCV, tuberculosis bacili and syphilis helicoid may cause significant increase of sMICA molecular in the serum of patients through some kind of mechanism; sMICA has some auxiliary diagnostic value in treating liver cancer, gram-negative bacilli, tuberculosis bacili, Hepatitis B virus, syphilis helicoid and Hepatitis C vims infection.②MICA*A5.1gene may be an important susceptibility gene leading to liver cirrhosis after infected with hepatitis B according to the positive correlation between MICA Exon5alleles A5.1and hepatitis b induced liver cirrhosis. Compared with the liver cirrhosis patients without MICA*A5.1, those with MICA*A5.1genes have a significantly higher serum levels of sMICA, indicating MICA*A5.1alleles take certain advantages in the production of serum sMICA molecules.③MICA Exon5alleles A5.1is positively correlated with liver cancer. Compared with liver cancer patients without MICA*A5.1, HCC patients with MICA*A5.1gene have significantly higher concentration of serum soluble MICA, indicating that the serum level of sMICA molecules is associated with the progress of liver cancer.④MICA Exon5gene polymorphism is uniformly distributed in liver cancer patients group and liver cirrhosis patients group. In both groups, levels of sMICA molecules in MICA*A5.1homozygous patients appeared to be greatly different from that in MICA*A5.1heterozygous patients. From the above results, it can be considered that serum sMICA molecular content is related to the progress of liver cirrhosis directing to liver cancer, and this is the function reflect of MICA Exon5alleles A5.1in protein levels. |
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