Trial reportOncotarget2015
SLC15A2 genomic variation is associated with the extraordinary response of sorafenib treatment: whole-genome analysis in patients with hepatocellular carcinoma.
Trial report in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
28 citing papers in PubMed.
- Integrative analysis and experimental validation of dioxin-interacting genes reveal diagnostic and prognostic biomarkers in lung adenocarcinoma.Clinical and experimental medicine · 2026Article
- Understanding exceptional response: The role of MINDY1 SNP in CDK4/6 inhibitor therapy for ERHGG advances · 2026Article
- Integrated in vivo combinatorial functional genomics and spatial transcriptomics of tumours to decode genotype-to-phenotype relationships.Nature biomedical engineering · 2026Article
- Upregulated E26 Transformation-Specific Variant Transcription Factor 7 in Oral Squamous Cell Carcinoma: Clinicopathological Correlations and Immune Regulatory Mechanisms.World journal of oncology · 2025Article
- Discovering the interactome, functions, and clinical relevance of enhancer RNAs in kidney renal clear cell carcinoma.BMC medical genomics · 2025Article
- Thai pharmacogenomics database -2 (TPGxD-2) sequel to TPGxD-1, analyzing genetic variants in 26 non-VIPGx genes within the Thai population.Clinical and translational science · 2024Article
- Genetic predisposition and high exposure to colistin in the early treatment period as independent risk factors for colistin-induced nephrotoxicity.Clinical and translational science · 2024Article
- Clinical trial design in the era of precision medicine.Genome medicine · 2022Review
- Current and emerging anti-angiogenic therapies in gastrointestinal and hepatobiliary cancers.Frontiers in oncology · 2022Review
- Genetic Heterogeneity, Therapeutic Hurdle Confronting Sorafenib and Immune Checkpoint Inhibitors in Hepatocellular Carcinoma.Cancers · 2021Review
- Minor Allele Frequencies and Molecular Pathways Differences for SNPs Associated with Amyotrophic Lateral Sclerosis in Subjects Participating in the UKBB and 1000 Genomes Project.Journal of clinical medicine · 2021Article
- The Hydrogen-Coupled Oligopeptide Membrane Cotransporter Pept2 is SUMOylated in Kidney Distal Convoluted Tubule Cells.Frontiers in molecular biosciences · 2021Article
- SLC15A4 Serves as a Novel Prognostic Biomarker and Target for Lung Adenocarcinoma.Frontiers in genetics · 2021Article
- Immunotherapy and Targeted Therapy for Hepatocellular Carcinoma: A Literature Review and Treatment Perspectives.Pharmaceuticals (Basel, Switzerland) · 2020Review
- Hepatocyte ploidy and pathological mutations in hepatocellular carcinoma: impact on oncogenesis and therapeutics.Global health & medicine · 2020Review
- Review
- Targeted therapy for hepatocellular carcinoma.Signal transduction and targeted therapy · 2020Review
- Limited bias effect of intratumoral heterogeneity on genetic profiling of hepatocellular carcinoma.Journal of gastrointestinal oncology · 2020Article
- Is the era of sorafenib over? A review of the literature.Therapeutic advances in medical oncology · 2020Review
- The genetic landscape of the human solute carrier (SLC) transporter superfamily.Human genetics · 2019Article
Corrections and comments
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Authors and funding
12 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Reliable biomarkers are required to predict the response to sorafenib. We investigated genomic variations associated with responsiveness to sorafenib for patients with unresectable hepatocellular carcinoma (HCC). Blood samples from 2 extreme, 2 strong and 3 poor responders to sorafenib were subjected to whole-genome analysis. Then, we validated candidate genomic variations with another 174 HCC patients, and performed in vitro functional analysis and in silico analyses. Genomic data of >96 gigabases/sample was generated at average of ~34X sequencing depth. In total, 1813 genomic variations were matched to sorafenib responses in clinical data; 708 were located within regions for sorafenib-target genes or drug absorption, distribution, metabolism, and excretion (ADME)-related genes. From them, 36 variants were within the coding regions and 6 identified as non-synonymous single-nucleotide variants from 4 ADME-related genes (ABCB1, FMO3, MUSK, and SLC15A2). Validation genotyping confirmed sequencing results and revealed patients genotype for rs2257212 in SLC15A2 showed longer progression-free survival (HR = 2.18). In vitro study displayed different response to sorafenib depending on the genotype of SLC15A2. Structural prediction analysis revealed changes of the phosphorylation levels in protein, potentially affecting sorafenib-associated enzymatic activity. Our finding using extreme responder seems to generate robust biomarker to predict the response of sorafenib treatment for HCC.
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