ArticlePloS one2013
Global gene expression profiling reveals SPINK1 as a potential hepatocellular carcinoma marker.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
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Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 68 citations in OpenAlex.
- Meta-analysis of gene expression profiles indicates genes in spliceosome pathway are up-regulated in hepatocellular carcinoma (HCC).Medical oncology (Northwood, London, England) · 2015Pooled it
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- Three-Dimensional Structure of Novel Liver Cancer Biomarker Liver Cancer-Specific Serine Protease Inhibitor Kazal (LC-SPIK) and Its Performance in Clinical Diagnosis of Hepatocellular Carcinoma (HCC).Diagnostics (Basel, Switzerland) · 2024Review
- Extraordinary variability in gene activation and repression programs during gonadal sex differentiation across vertebrates.Frontiers in cell and developmental biology · 2024Article
- A novel diagnostic four-gene signature for hepatocellular carcinoma based on artificial neural network: Development, validation, and drug screening.Frontiers in genetics · 2022Article
- Novel Molecular Targets for Hepatocellular Carcinoma.Cancers · 2021Article
- Performance of SPINK1 and SPINK1-based diagnostic model in detection of hepatocellular carcinoma.Journal of clinical laboratory analysis · 2021Article
- A hierarchical dynamic model used for investigating feed efficiency and its relationship with hepatic gene expression in APOE*3-Leiden.CETP mice.Physiological reports · 2021Article
- Evaluation of heat stress effects on cellular and transcriptional adaptation of bovine granulosa cells.Journal of animal science and biotechnology · 2020Article
- Fermentable fiber-induced hepatocellular carcinoma in mice recapitulates gene signatures found in human liver cancer.PloS one · 2020Article
- Overexpression of Hepatocyte Chemerin-156 Lowers Tumor Burden in a Murine Model of Diethylnitrosamine-Induced Hepatocellular Carcinoma.International journal of molecular sciences · 2019Article
- Dynamic edge-based biomarker non-invasively predicts hepatocellular carcinoma with hepatitis B virus infection for individual patients based on blood testing.Journal of molecular cell biology · 2019Article
- HBx-K130M/V131I Promotes Liver Cancer in Transgenic Mice via AKT/FOXO1 Signaling Pathway and Arachidonic Acid Metabolism.Molecular cancer research : MCR · 2019Article
- A novel tumor suppressor SPINK5 targets Wnt/β-catenin signaling pathway in esophageal cancer.Cancer medicine · 2019Article
- Classification of early and late stage liver hepatocellular carcinoma patients from their genomics and epigenomics profiles.PloS one · 2019Article
- Identification of Platform-Independent Diagnostic Biomarker Panel for Hepatocellular Carcinoma Using Large-Scale Transcriptomics Data.Frontiers in genetics · 2019Article
- Bad Tumors Made Worse: SPINK1.Frontiers in cell and developmental biology · 2019Article
- Hepatitis B Virus X Protein-Induced Serine Protease Inhibitor Kazal Type 1 Is Associated with the Progression of HBV-Related Diseases.BioMed research international · 2019Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundLiver cirrhosis is the most important risk factor for hepatocellular carcinoma (HCC) but the role of liver disease aetiology in cancer development remains under-explored. We investigated global gene expression profiles from HCC arising in different liver diseases to test whether HCC development is driven by expression of common or different genes, which could provide new diagnostic markers or therapeutic targets. METHODOLOGY AND PRINCIPAL
findingsGlobal gene expression profiling was performed for 4 normal (control) livers as well as 8 background liver and 7 HCC from 3 patients with hereditary haemochromatosis (HH) undergoing surgery. In order to investigate different disease phenotypes causing HCC, the data were compared with public microarray repositories for gene expression in normal liver, hepatitis C virus (HCV) cirrhosis, HCV-related HCC (HCV-HCC), hepatitis B virus (HBV) cirrhosis and HBV-related HCC (HBV-HCC). Principal component analysis and differential gene expression analysis were carried out using R Bioconductor. Liver disease-specific and shared gene lists were created and genes identified as highly expressed in hereditary haemochromatosis HCC (HH-HCC) were validated using quantitative RT-PCR. Selected genes were investigated further using immunohistochemistry in 86 HCC arising in liver disorders with varied aetiology. Using a 2-fold cut-off, 9 genes were highly expressed in all HCC, 11 in HH-HCC, 270 in HBV-HCC and 9 in HCV-HCC. Six genes identified by microarray as highly expressed in HH-HCC were confirmed by RT qPCR. Serine peptidase inhibitor, Kazal type 1 (SPINK1) mRNA was very highly expressed in HH-HCC (median fold change 2291, p = 0.0072) and was detected by immunohistochemistry in 91% of HH-HCC, 0% of HH-related cirrhotic or dysplastic nodules and 79% of mixed-aetiology HCC.
conclusionHCC, arising from diverse backgrounds, uniformly over-express a small set of genes. SPINK1, a secretory trypsin inhibitor, demonstrated potential as a diagnostic HCC marker and should be evaluated in future studies.
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