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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

