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Gene & Protein in Disease                                           Pre-metastatic niche oral cancer: Insights












































            Figure 1. Representative immunohistochemical staining characteristics of SERPINE1, SPP1, L1CAM, PER3, and BHLHE40 expressions in normal and oral
            cancer patients. Data were extracted from The Human Protein Atlas (https://www.proteinatlas.org/)


            genome-wide biological data with molecular networks   pattern in DEGs and revealing their association with 473
            is essential for elucidating the complex mechanisms and   pre-metastatic-related genes. DAVID functional analysis
            molecular signatures linked to various disease subtypes.   of the combined pre-metastatic-related gene list and DEGs
            Several studies have identified biomarkers associated   showed the activation of multiple pathways involved in
            with cancer  invasion, migration, and metastasis in oral   cancer development. A  particularly striking observation
            cancer. 1,11,23,24  However, only a few have performed meta-  from  our  lymph  node  analysis  was  the  inactivation of
            analyses that encompass transcriptomic data from normal,   immune response pathways in metastatic lymph nodes,
            cancerous, and lymph node samples. Our previous study   coupled with the upregulation of genes linked to cancer
            demonstrated overexpression of organ-specific metastasis-  pathways and circadian rhythm. The upregulation of genes
            associated proteins in non-metastatic lymph nodes.  These   associated with Schwann cell dedifferentiation in metastatic
                                                     8
            proteins can modify the microenvironment, attracting   and perineural invasion-positive tumors underscores the
            tumor  cells  and  facilitating  their  establishment  within  a   multifaceted nature of OSCC metastasis.
            pre-metastatic niche. 1,4
                                                                 The molecular mechanisms related to the circadian
              The purpose of our study was to identify the molecular   rhythm in metastatic progression have been documented
            mechanisms governing the pre-metastatic niche in OSCC.   in tumor samples. 25-27  A previous study demonstrated that
            Employing a variety of analytical methods, we identified   the expression patterns of circadian rhythm genes, such as
            DEGs in healthy oral tissues and OSCC, non-metastatic   PER2 or BMAL1, are correlated with lymph node metastasis
            and metastatic primary tumors, and normal and metastatic   in breast cancer.  These genes are involved in melatonin
                                                                            26
            lymph nodes. Our results indicate that the upregulated                                   28,29
            genes in primary tumor samples were closely associated   production, a key regulator of circadian rhythm.
            with cancer pathways. Validation through TCGA data   Melatonin, an antioxidant released in response to
            confirmed  these  findings,  demonstrating  a  consistent   light, plays a significant role in sleep regulation. 30,31


            Volume 3 Issue 4 (2024)                         17                              doi: 10.36922/gpd.2971
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