Abstract 298: Senescence-associated gene expression in head and neck cancer in TCGA samples
Authors: Sanjana Arji, Beverly R. Wuertz, Frank G. Ondrey
Journal: Cancer Research (2025)

Abstract Introduction: Senescent cells in tumors constitute an important cell population that may be both anti- and pro-tumorigenic. Head and neck cancer (HNC) is associated with treatment resistance, recurrence, and decreased survival rates that are somewhat stagnant. We examined the TCGA for differences in senescence-associated genes using various parameters. Methods: 83 established HNC senescence-associated genes were examined in the TCGA Pancancer Atlas dataset via CBioPortal. mRNA expression (RSEM; Batch normalized from Illumina HiSeq_RNASeqV2) for each of the genes of interest was examined. Demographic information, disease stage, and HPV subtype data were also collected. Student's t-tests were conducted using RStudio's tidyverse package to determine statistically differentially expressed genes (p &amp;lt; 0.05). Then, Gene Ontology, through DAVID Bioinformatics, was conducted on the set of statistically significant genes found from each comparison to determine overexpressed pathways and adjusted p-values post-Benjamini-Hochberg correction (q &amp;lt; 0.05). Results: Considering HPV Status: 65/83 of the tested genes statistically differed between HPV+ and HPV-. Out of the 65 significant genes, 6 were related to peptidyl-serine phosphorylation: TOP1, NEK6, LATS2, MAPK1, MAP4K1, TGFBR1(p = 4.3E-5; q = 1.7E-2), 5 were related to the G1/S transition of the mitotic cell cycle: CCND1, CDK6, CDKN1A, EZH2, LATS2 (p = 2.7E-5; q = 1.7E-2), and 5 were related to canonical WNT signaling pathway: YAP1, CAV1, LATS1, PTEN, SIAH1(p = 1.7e-4; q = 3.5E-2). Considering Caucasian vs African American, HSPA5 (p=0.02), NEK6 (p = 0.0163), and SMURF1 (p = 0.0015) were all found to be statistically significant. SMURF1 and HSPA5 were found to negatively regulate the TGF-beta receptor signaling pathway (p = 1.3e-2; q = 7.6e-1). Considering 1st vs 4th quartile age: SERPINE1 (p = 0.00301), POU5F1 (p = 0.0063) and CDKN2A (p = 0.0653) were differentially expressed. No overexpressed pathways were noted in the Gene Ontology Biological Process Analysis. Considering tumor stage: AREG (p=0.01405), GAPDH (p = 0.01475), PSMB5 (p = 0.04848), LIMA1 (p = 0.04709), EHF (p = 0.03858), and DPY30 (p = 0.003711) were found to be differentially expressed. However, no overexpressed pathways were found in Gene Ontology Biological Process Analysis. Conclusions: We identified various statistically different senescence-associated markers between various parameters in our analysis of TCGA-associated data. Furthermore, four overexpressed pathways were identified through gene ontology of statistically significant genes between HPV status and race. Identifying these pathways and genes may help better understand variations in HNC presentation and create more definitive senescent markers to determine prognosis based on these parameters. Further analysis of the genes with higher stringency thresholds and consideration of epigenetic factors must be done to solidify the findings. Citation Format: Sanjana Arji, Beverly R. Wuertz, Frank G. Ondrey. Senescence-associated gene expression in head and neck cancer in TCGA samples [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 298.