Biomedical subjects

Jihye Park

Publications and source records attributed to Jihye Park.

3 recordsLinked to original sources

PubMed2026

Transcriptome-based epigenetic screening identifies DNA hypermethylation signatures as prognostic biomarkers in oral squamous cell carcinoma.

Promoter DNA hypermethylation is a key epigenetic mechanism of gene silencing in cancer, yet the DNA hypermethylome of oral squamous cell carcinoma (OSCC) and its prognostic relevance remain poorly characterized. Here, we systematically identified and validated novel hypermethylated genes with prognostic significance in OSCC using a genome-wide discovery and multi-platform validation strategy. Candidate genes were first identified by pharmacologic demethylation combined with RNA sequencing across OSCC cell lines, then validated by quantitative RT-PCR, methylation-specific PCR, and bisulfite sequencing in OSCC cell lines, normal oral mucosa, and primary OSCC tumors, with independent confirmation in the TCGA-HNSC dataset. Immunohistochemistry confirmed protein-level silencing, and Kaplan-Meier survival analysis assessed prognostic significance across both cohorts. This pipeline identified five candidate genes, GPX3, ANG, CTGF, GPRC5B, and BAMBI, exhibiting cancer-specific promoter hypermethylation associated with transcriptional and protein silencing in OSCC. Validation in oral cavity tumor samples extracted from the TCGA-HNSC dataset confirmed tumor-specific hypermethylation and revealed significant inverse correlations between methylation and expression for GPX3, GPRC5B, and CTGF. Notably, CTGF hypermethylation was independently associated with poor overall survival in both cohorts (institutional cohort, p=0.03; oral tumor subset from TCGA-HNSC, p=0.01), and a combined ANG+CTGF methylation signature showed superior and reproducible prognostic performance across both platforms. Pathway analysis linked these genes to epithelial-mesenchymal transition and interferon response signaling. This study establishes the first validated DNA methylation biomarker panel for OSCC prognosis, identifying CTGF hypermethylation as a robust prognostic driver with translational potential for clinical risk stratification.

Humans↗

PubMed2026

Distinct endogenous retroviruses are expressed in mutational subtypes of clear cell renal cell carcinoma and are linked to improved clinical outcomes.

Distinct mutations in chromatin regulators and aberrant expression of transposable elements (TEs), have been associated with clinical benefit to immunotherapy (IO) in specific clear cell renal cell carcinoma (ccRCC) clinical contexts. However, the relationship between mutations in chromatin regulators and TE expression, and their effect on clinical outcomes, are incompletely understood. Here, we identified TEs expressed in distinct mutational subtypes of ccRCC, with endogenous retroviruses (ERVs) comprising the majority of TEs observed. Of these, ERVs 544 and 2014 were upregulated in PBRM1 mutant samples. Patients with high expression of these ERVs and somatic PBRM1 mutations had improved progression-free survival with IO monotherapy, but not targeted therapy, and their upregulation associated with expression of innate immune pathways. Chromatin accessibility increased at ERV 544 and 2014 loci in PBRM1-deficient ccRCC cells, and ERV 544 and 2014 were upregulated upon in vitro PBRM1 knockout in ccRCC cell line clones. Broadly, our study supports a link between PBRM1 mutations, subsequent chromatin accessibility changes, and aberrant but immunoresponsive ERVs in ccRCC.

CP: cancer↗

PubMed2026

Diverse mediators of cancer predisposition uncovered by germline whole genome sequencing of unexplained familial cancers.

Cancer frequently clusters in families due to shared environment and genetics. However, many familial cancer cases lack a clinically recognized pathogenic germline variant (PGV). We analyzed germline genomes and family history from 2,726 individuals without a PGV in the All of Us Research Program, including 1,496 cases across 18 cancer types with extensive family history and 1,230 family history-negative, cancer-free controls. We identified allelic series of rare structural variants inactivating MSH2 in individuals with phenotypes consistent with Lynch syndrome and BRCA1 in breast cancer. Cancer polygenic risk scores were enriched in cases and correlated with patterns of cancer diagnoses within families. Exome-wide rare variant analyses nominated six candidate predisposition genes, including TSTD2 and BRAT1 in thyroid and breast cancer, respectively. Overall, polygenic risk and rare variants impacting known genes explained a median of 5% of unexplained familial cancers, increasing to 11% when including newly nominated risk factors.

Journal Article↗