A key genomic signature associated with lymphovascular invasion in head and neck squamous cell carcinoma

Abstract

Background: Lymphovascular invasion (LOI), a key pathological feature of head and neck squamous cell carcinoma (HNSCC), is predictive of poor survival; however, the associated clinical characteristics and underlying molecular mechanisms remain largely unknown. Methods: We performed weighted gene co-expression network analysis to construct gene co-expression networks and investigate the relationship between key modules and the LOI clinical phenotype. Functional enrichment and KEGG pathway analyses were performed with differentially expressed genes. A protein-protein interaction network was constructed using Cytoscape, and module analysis was performed using MCODE. Prognostic value, expression analysis, and survival analysis were conducted using hub genes; GEPIA and the Human Protein Atlas database were used to determine the mRNA and protein expression levels of hub genes, respectively. Multivariable Cox regression analysis was used to establish a prognostic risk formula and the areas under the receiver operating characteristic curve (AUCs) were used to evaluate prediction efficiency. Finally, potential small molecular agents that could target LOI were identified with DrugBank.

Identification of miR-203a, mir-10a, and miR-194 as predictors for risk of lymphovascular invasion in head and neck cancers

“…LVI has been established as an important indicator of disease outcome and treatment modalities in several cancers [ 8 , 29 ]. In HNSC, LVI is a well-known clinic-pathological feature that tends to adversely influence disease prognosis and negatively affect patient survival and is the primary indicator of lymph node metastasis [ 11 , 13 ]. Increased lymphangiogenesis is closely related with enhanced LVI and subsequent distant dissemination [ 10 ].…”

“…Thus, regulation of these pathways could have significant impact on LVI and subsequent lymph node metastasis and patient outcome. In one study, weighted gene co-expression network analysis was used to construct gene co-expression networks and investigate the relationship between key modules and the LVI clinical phenotype and identified 24 genes in the metabolic and immune reprogramming [ 13 ]. This is interesting all the miRNAs (miR-194, miR-10a and miR 203a) that show significant association with LVI in our study also regulate metabolic pathways and alteration of immune cell response that are known to remodel the metastatic lymph node [ 72 – 74 ].…”

“…LVI is a histopathological feature that established as an independent predictor of poor prognosis and lymph node metastasis (LNM) in several solid tumors. Although different molecular signatures are associated with HNSCC, most studies have typically overlooked the association of any molecular, genetic or clinical features with LVI and the factors contributing to LVI remain very poorly understood [11][12][13].…”

Molecular Characterization and Clinical Relevance of Lysine Acetylation Regulators in Urological Cancers

“…To validate the protein expression of differentially expressed genes and activity of cell cycle and oxidative phosphorylation related pathway, as per the method described by our previous study (23), the protein of EP300, cyclin dependent kinases 2 (CDK2), cyclin A2 (CCNA2), NADH ubiquinone oxidoreductase complex assembly factor 8 of complex I (NDUFB8) and succinate dehydrogenase complex iron sulfur subunit B of complex II (SDHB) in TGCT, kidney_Tumor, BLCA and PRAD were clarified by immunohistochemistry analysis. All captured images were manually annotated by certified pathologists.…”

Cyclin-dependent kinase inhibitors in head and neck cancer and glioblastoma—backbone or add-on in immune-oncology?

“…Of note, AT7519 likewise reduced phosphorylation of RNA polymerase II via CDK1/9 and affected expression levels of the oncoprotein N-Myc, making this compound a candidate for treatment of N-Myc-driven cancers. Zhang et al recently identified AT7519 for controlling lymphovascular invasion in HNSCC patients [86]. Clinical trials are on the way to prove efficacy in HNSCC and other malignancies (STable 1).…”