The Role Of MUC16 In Nasopharyngeal Carcinoma And The Association Between MUC16 And Epstein-Barr Virus

OBJECTIVE MUC16 is a kind of high molecular weight cell surface glycoprotein,which is expressed in human normal airway epithelium and secreted mainly by goblet cells and mucus cells of submucous gland.At present,the regulatory mechanism of MUC16 has been studied in ovarian,breast,pancreatic and non-small cell lung cancer.The results show that MUC16 is overexpressed in tumor,but its role in nasopharyngeal carcinoma is not clear.Nasopharyngeal carcinoma is a type of malignant tumor that occurs at the upper and lateral walls of the nasopharyngeal cavity and it has the highest incidence of all types of otolaryngopharyngeal malignant tumor.There is a low incidence of nasopharyngeal carcinoma in the West,but a high incidence in Southeast Asia,particularly in Guangzhou,China.Among the tissue types of nasopharyngeal carcinoma,the non-keratinized subtype accounts for more than 95% of cases and is closely associated with Epstein-Barr virus infection.Epstein-Barr virus is a widespread virus that affects approximately 95% of the population worldwide.Under normal circumstances,Epstein-Barr virus is a latent infection.When nasopharyngeal epithelial cells are cancerous,the virus has been detected in the tumor cells,suggesting that Epstein-Barr virus infection is a risk factor for nasopharyngeal carcinoma.But the association between MUC16 and Epstein-Barr virus is not clear.In the present study,the role of MUC16 in nasopharyngeal carcinoma and the association between MUC16 and Epstein-Barr virus were investigated.METHODS 40 nasopharyngeal carcinoma specimens and 30 normal nasopharyngeal tissue specimens from the Department of Otorhinolaryngology,affiliated Hospital of Qingdao University were collected and fixed with formalin and embedded in paraffin.2 fresh NPC tissues(Q34 and Q36)and 4 fresh normal nasopharyngeal tissues(Q1,Q3,Q5 and Q6)from the Department of Otolaryngology,Affiliated Hospital of Qingdao University were used for q RT-PCR.Further,2 fresh NPC tissues(Q34 and Q36)and 3 fresh normal nasopharyngeal tissues(Q3,Q5 and Q6)were used for western blotting.Three NPC cell lines(C666 is an EBV-positive cell line,and HONE and CNE are EBV-negative cell lines)and six gastric carcinoma(GC)cell lines(GT38,GT39 and SUN719 are EBV-positive cell lines,and AGS,BGC-823 and SGC-7901 are EBV-negative cell lines)were used to analyze the relationship between MUC16 and Epstein-Barr virus infection.q RT-PCR and western blot analysis were conducted in cell lines and tumor samples.The clinical significance of MUC16 was evaluated usingimmunohistochemistry.RESULTS MUC16 was downregulated in the nasopharyngeal carcinoma tissues(Q34 and Q36)compared with the normal nasopharyngeal tissues(Q3,Q5 and Q6)which suggests that MUC16 is associated with the development of nasopharyngeal carcinoma at both the m RNA and protein levels(P<0.05).In addition,the experimental data indicated that MUC16 was significantly down regulated in the EBV-positive NPC cell lines(C666)compared with the EBV-negative NPC cell lines(HONE,CNE),in the EBV-positive gastric carcinoma cell lines(GT38,GT39 and SUN719)compared with the EBV-negative gastric carcinoma cell lines(AGS,BGC-823 and SGC-7901)(P<0.05).The immunohistochemistry staining indicated that MUC16 was located in the apical membrane of the ciliated cells of the normal nasopharyngeal epithelium.When comparing the MUC16 composite scores of the normal nasopharyngeal epithelium specimens with those of the NPC specimens,the difference was significant(P<0.05).Based on these date,low expression of MUC16 may be associated with EBV infection.CONCLUSION The findings of the present study indicate downregulated expression of MUC16 may be associated with NPC,and EBV infection may induce MUC16 downregulation at the m RNA and protein levels.Thus,MUC16 may participate in the development of NPC,and may promote NPC through EBV infection.However,the specific mechanism and pathway between MUC16 and NPC,and MUC16 and EBV remain unknown.MUC16 may be used as a tumor marker for NPC in the future.