An Initial Indonesian Genome-Wide SNP-Array Study with Functional Variant Prioritization Reveals NASP and GPR78 Candidate SNVs in Hepatocellular Carcinoma
Penulis:Â Lalisang, Toar Jean Maurice;Â Marbun, Vania Myralda Giamour;Â Erlina, Linda;Â Zacharia, Nathaniel Jason;Â Allo, Kezia Nathania Limbong
Informasi
JurnalBiomedicines
PenerbitMultidisciplinary Digital Publishing Institute (MDPI)
Volume & EdisiVol. 14,Edisi 4
Halaman -
Tahun Publikasi2026
ISSN22279059
Jenis SumberScopus
Abstrak
Background/Objectives: Population-specific genomic data are essential for understanding hepatocellular carcinoma (HCC) biology, particularly in underrepresented regions. This study aimed to perform exploratory single-nucleotide polymorphism (SNP)-array-based profiling of HCC tumor samples from Indonesian patients and to prioritize candidate functional variants using a systematic in silico framework. Methods: This retrospective cross-sectional study included 15 resected HCC cases with available formalin-fixed paraffin-embedded (FFPE) tumor tissue. Genome-wide SNP genotyping was performed using the Illumina Asian Screening Array. Following quality control and filtering, variants were annotated using the Ensembl Variant Effect Predictor. A case-only functional prioritization approach incorporating multiple in silico prediction tools was applied, followed by gene-level burden aggregation. Results: After multistep filtering, 11 samples and 104 prioritized variants were retained for analysis. Variants consisted predominantly of splice-region, missense, and regulatory changes. Gene-level burden analysis identified Nuclear Autoantigenic Sperm Protein (NASP, rs775916096) as the highest-ranked candidate gene, while G protein-coupled receptor 78 (GPR78, rs558447540) emerged as a secondary candidate with predicted functional annotations but currently limited biological evidence in HCC. Given the tumor-only design without matched normal tissue, the prioritized variants cannot be distinguished from rare germline variants. Conclusions: This exploratory SNP-array study provides a hypothesis-generating framework for functional variant prioritization in Indonesian HCC. NASP and GPR78 represent preliminary candidates that require validation in larger cohorts with matched normal tissue and sequencing-based confirmation. © 2026 by the authors.
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