Advances in Cancer Biology - Metastasis (Dec 2022)
Systemic aftermaths of tobacco addiction on the physiological composite of human secretome and the prognostic potential of U2AF26 in oral cancers
Abstract
Objectives: Tobacco chewing and smoking practices have been a common trend among human populations. Tobacco addiction is a commonly known etiology for oral cancers. The study showcases a clinical case (I_5; a 36y male) with a chronic inflamed persistent oral lesion and positive addiction history of tobacco chewing & smoking to screen out a prognostic target for oral malignancy. Method: Two-dimensional gel electrophoreses (2DE), using the depleted serum proteome of I_5 and healthy control, were performed for resolving the complex protein repertoire of the secretome. MALDI-TOF-MS and in-silico peptide analyses were used for characterizing the 2DE protein spot of interest. The relative real-time PCR, used for validation of the modulations in the expression of the gene of interest, involved oral cancer (n = 14) and pre-cancer lesions (n = 9). The adjacent normal tissues (encircling oral diseased lesions) and healthy oral epithelia were used as the controls. Results: The comparative analysis of 2DE profiles uncovered substantial disparities between the depleted secretome of the case (I_5) and the control. The qualitative differential spot ‘a’ (absent in I_5 but present in healthy control) corresponding to HNCUP U2AF26-III was found to down-regulate in the serum proteome of OSCC cases (both tobacco addicts & non-addicts) compared to healthy non-addicts. Also, the expression of the nccpU2AF26 showed significant down-regulation in oral-precancerous and cancerous samples in comparison with the healthy oral epithelia while the expression levels were found to be significantly up-regulated when lesions were compared with their adjacent normal tissues. Conclusions: The serum proteome of a chronic tobacco addict deficits in multiple proteins constituting the physiological human secretome. The U2AF26-III may function as a prognostic biomarker and therapeutic target for oral malignancies. Also, a non-canonical transcript (nccpU2AF26) lacking exon 3 and 4 was identified to be present in normal oral epithelia and POLs, highlighting the need for rigorous analyses of the role(s) played by U2AF26 non-canonical isoform(s) in the genesis of oral precancer and cancer lesions.
