Downregulation of tapasin expression in primary human oral squamous cell carcinoma: association with clinical outcome.
MHC class I peptide loading complex defects are frequently observed in tumor cells which facilitate tumor cells escaping from immune surveillance. Tapasin plays an important role in the assembly of MHC class I molecules with peptides in the endoplasmic reticulum. The aim of this study was to investigate the expression of tapasin in primary oral squamous cell carcinoma (OSCC) and its potential clinical implication. Formalin-fixed, paraffin-embedded tumor biopsies from 67 patients with primary OSCC were analyzed for tapasin expression using immunohistochemistry. Tapasin promoter methylation status in OSCC cell lines was determined using ethylation-specific polymerase chain reaction, bisulphate genomic sequencing, and expression reactivation assay. Lack of tapasin expression was observed in 30 of 67 (43%) tumors and was significantly associated with poor pathologic differentiation grade of OSCC (P = 0.028). The cumulative 5-year survival rate was also significantly correlated with pathologic differentiation grade (P = 0.001) and tapasin expression level (P = 0.015). Decreased tapasin expression was an indicator of poor survival (P = 0.048). Tapasin promoter methylation was observed in all three OSCC cell lines examined, and the mRNA and protein levels of tapasin increased markedly after treatment with 5-aza-2'-deoxycytidine. Downregulation of tapasin is associated with a poor clinical outcome for OSCC patients and may serve as a prognostic biomarker. The promoter methylation may contribute to the tapasin downregulation in OSCC.
Department of Oral and Maxillofacial Surgery, Ninth People's Hospital, College of Stamotology, Shanghai Jiao Tong University School of Medicine, Shanghai Research Institute of Stomatology, Shanghai, 200011, China.
Qian
Q
Jiang
Hong-ya
HY
Pan
Dong-xia
DX
Ye
Ping
P
Zhang
Lai-ping
LP
Zhong
Zhi-yuan
ZY
Zhang
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D026901:Membrane Transport Proteins / Q000096:biosynthesis*; D008875:Middle Aged; D008969:Molecular Sequence Data; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult
D014408:Biomarkers, Tumor; D026901:Membrane Transport Proteins; C107762:tapasin