Tobacco-Associated Dysregulation in TAP-1 and TAP-2 Expression in Oral Premalignant Lesions and Oral Squamous Cell Carcinoma

Document Type : Research Articles

Authors

1 Department of Medical Laboratory Technology, School of Allied Health Sciences, Galgotias University, Greater Noida, Uttar Pradesh, India.

2 Department of Biochemistry, All India Institute of Medical Sciences, Gorakhpur, Uttar Pradesh, India.

3 Department of Radiotherapy, All India Institute of Medical Sciences, Gorakhpur, Uttar Pradesh, India.

4 Department of E.N.T, All India Institute of Medical Sciences, Gorakhpur, Uttar Pradesh, India.

5 Department of Pathology, All India Institute of Medical Sciences, Gorakhpur, Uttar Pradesh, India.

6 Department of Dentistry, All India Institute of Medical Sciences, Gorakhpur, Uttar Pradesh, India.

7 Department of Biochemistry, Rajiv Gandhi Medical College Thane Kalva, Maharashtra, India.

Abstract

Background: TAP-1, and TAP-2 are required for MHC class I–restricted antigen surveillance. Downregulated TAP expression in oral carcinogenesis might affect the antigen presentation system, leading to immune evasion. Tobacco is the most common aetiologic risk factor for Oral Squamous Cell Cancer, and it could influence antigen-processing mechanisms throughout the stages of Oral Squamous Cell Cancer. Materials and Methods: This hospital-based case-control study included 60 cases of oral squamous cell carcinoma (OSCC), 60 oral premalignant lesions, and 60 age and sex-matched healthy controls. A standardised questionnaire was used to collect information about tobacco exposure patterns. Before beginning treatment, peripheral blood samples were taken. Total RNA was extracted and reverse-transcribed, and TAP-1 and TAP-2 gene expression was measured using SYBR Green-based real-time PCR, with relative gene expression calculated using the 2-ΔΔCt method with normalization to the housekeeping gene. Non-parametric tests and multivariate linear regression was used for statistical analysis. Results: Combined tobacco users were most common among OSCC (50–55%), with about 88.3% of controls being non-users. TAP-1 expression demonstrated a significant decrease in leukoplakia smokeless tobacco-related (mean = 0.80; p = 0.048), and with the OSCC dedifferentiation, which was even lower in poorly differentiated tumours (mean = 0.68; p = 0.029). Expression of TAP-2 was not altered in premalignant conditions, whereas it was remarkably decreased in OSCC patients with mixed tobacco habit (mean = 0.85; p = 0.044). Multivariate analysis revealed an independent effect of mixed tobacco on lower TAP expression, as well as a role for grade (p < 0.05). Conclusion: Simultaneous tobacco exposure induces a modest but significant decline in TAP-2 with differentiation-dependent reduction of TAP-1, suggesting that the subtle dysfunction in antigen processing machinery during oral carcinogenesis.

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