Abstract B041: Hypoxia up-regulated protein 1 and its related genes as potential prognostic markers in papillary thyroid cancer
Abstract
Papillary thyroid cancer (PTC) exhibits differences in incidence, recurrence, and survival among racial and ethnic groups, suggesting underlying molecular mechanisms contributing to disease progression. In a previous bulk RNA-sequencing study of the Loma Linda University cohort, we identified Hypoxia up-regulated protein 1 (HYOU1) as differentially expressed among four ethnic groups. HYOU1 is a gene involved in protein folding and adaptation during hypoxia and endoplasmic-reticulum stress. HYOU1 expression has been associated with tumor-cell survival, disease progression, and poor clinical outcomes in several malignancies. We hypothesized that HYOU1 and its related genes are associated with papillary thyroid cancer progression and survival. The Cancer Genome Atlas (TCGA) thyroid carcinoma datasets were analyzed using the University of Alabama at Birmingham Cancer (UALCAN) data analysis platform to evaluate HYOU1 and its positively correlated genes for tumor-versus-normal expression, race, sex, tumor stage, survival, and thyroid cancer cell-line dependency. Three positively correlated genes-SRPRB, DDOST, and TTC30A-were selected based on Pearson correlation strength, expression differences, survival associations, and DepMap gene-effect scores. HYOU1 was significantly downregulated in thyroid tumors and demonstrated reduced expression across racial, sex, and tumor-stage subgroups. Higher tumor expression was associated with poorer overall survival. DepMap CRISPR-knockout analysis showed that loss of HYOU1 reduced the viability of several thyroid cancer cell lines, suggesting these cells may depend on HYOU1 for survival. These three correlated genes were also downregulated in thyroid tumors, associated with poorer survival, and showed similar dependency in DepMap thyroid cancer cell lines. SRPRB and DDOST are involved in endoplasmic-reticulum protein targeting and processing, whereas TTC30A functions in ciliary transport. HYOU1 and its related gene expressions in the LLU cohort were confirmed using RT-qPCR. HYOU1, SRPRB, DDOST, and TTC30A were consistently downregulated in thyroid tumors compared to normal tissue across multiple clinical subgroups, including race, sex, and tumor stage. Elevated expression of each gene was significantly associated with poorer overall survival in TCGA PTC patients. CRISPR-knockout dependency mapping revealed that loss of any of these four genes reduced viability in multiple thyroid cancer cell lines, indicating a potential functional reliance on these genes for tumor cell survival. RT-qPCR validation in the LLU cohort confirmed the differential expression pattern of HYOU1 observed in the TCGA analysis. These findings suggest that HYOU1, SRPRB, DDOST, and TTC30A may serve as potential prognostic markers in papillary thyroid cancer. Additional studies are needed to determine their potential as prognostic biomarkers or therapeutic targets. Olabisi T. Bamidele, James Kuo, Samuel Chan, Luiza Barseghyan, Celena R. Yamauchi, Alfred A. Simental, Salma Khan. Hypoxia up-regulated protein 1 and its related genes as potential prognostic markers in papillary thyroid cancer [abstract]. In: Proceedings of the 19th AACR Conference on the Science of Cancer Health Disparities; 2026 Oct 18-21; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2026;35(10 Suppl):Abstract nr B041.
