Advances in Cancer Biology - Metastasis (Oct 2021)
Molecular winnowing, expressional analyses and interactome scrutiny of cellular proteomes of oral squamous cell carcinoma
Abstract
Background: Oral cancer is one of the highly aggravated conditions of oral pathologies. The commonly diagnosed form of oral cancer is oral squamous cell carcinoma (OSCC). The molecular players responsible for low post-treatment cancer-free survival rate and higher recurrence & metastasis rates associated with OSCC are still obscure. This study aims to perform comparative analyses of the cellular proteome of cancer lesion and adjacent normal tissue of OSCC clinical cases to identify protein(s) and gene(s) players functional during oral carcinogenesis. Material and methods: The cellular proteomes were resolved by one & two-dimensional gel electrophoreses (2DE). The protein(s) of interest were characterized by MALDI-TOF MS PMF. The in-silico analyses of identified peptide sequences were performed. The expressional scrutiny of target gene(s) was carried out using relative quantitative polymerase chain reaction methodology. Also, the interactome analysis of target gene(s) was accomplished. Results: The standardized 2DE protocol enabled the separation of proteins constituting the cellular proteome of OSCC lesions and adjacent normal tissues. Six differentially expressed 2DE protein spots were identified as followed SWT1, TMOD3, IFIT2, COL4A2, MMTAG2, and MIC27. The relative expression of MMTAG2, IFIT2, and COL4A2 genes/transcripts were up-regulated and SWT1, TMOD3, and MIC27 genes/transcripts were down-regulated in cancer cDNA pools in comparison to cDNA pools observed in healthy oral epithelium. The interaction network generated for target genes/proteins comprised of cancer-associated genes like AKTs, MAPKs, STATs, indicating the crucial involvement of target genes in malignant pathology of the oral cavity. Conclusions: The involvement of SWT1, TMOD3, IFIT2, COL4A2, MMTAG2, & MIC27 genes was found to be significant in oral carcinogenesis implicating their potential candidature as diagnostic and therapeutic markers. The normal oral mucosa surrounding OSCC lesions undergoes a proteome molecular shift similar to the adjoining OSCC tumors.
