ArticlePathology oncology research : POR2015
Differential Expression of Sonic Hedgehog Protein in Human Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma.
Article in Pathology oncology research : POR, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 2 of them syntheses that pooled it.
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Who cites it
15 citing papers in PubMed, 2 syntheses or guidelines pooled it, 26 citations in OpenAlex.
- Does Oral Microbiota Have a Close Relationship with Pancreatic Cancer? A Systematic Review and Meta-Analysis.Annals of surgical oncology · 2023Pooled it
- Mitochondrial Dysfunction and Induction of Apoptosis in Hepatocellular Carcinoma and Cholangiocarcinoma Cell Lines by Thymoquinone.International journal of molecular sciences · 2022Pooled it
- Greater susceptibility of patients with idiopathic pulmonary fibrosis to basal cell carcinoma: a combined genomics and Mendelian randomization analysis.Translational cancer research · 2026Article
- Molecular Alterations and Pathways in Intrahepatic Cholangiocarcinoma: Available Evidence and New Perspectives.International journal of molecular sciences · 2025Review
- Signaling pathways in liver cancer: pathogenesis and targeted therapy.Molecular biomedicine · 2024Review
- The Role of the Hedgehog Pathway in Cholangiocarcinoma.Cancers · 2021Review
- The microbiota of the bilio-pancreatic system: a cohort, STROBE-compliant study.Infection and drug resistance · 2019Article
- Molecular pathways of nonalcoholic fatty liver disease development and progression.Cellular and molecular life sciences : CMLS · 2019Review
- The expressions of Hedgehog and PI3K-AKT pathway components correlate with invasion and metastasis in hepatocellular carcinoma.International journal of clinical and experimental pathology · 2019Article
- The hedgehog pathway in nonalcoholic fatty liver disease.Critical reviews in biochemistry and molecular biology · 2018Review
- A nomogram incorporating six easily obtained parameters to discriminate intrahepatic cholangiocarcinoma and hepatocellular carcinoma.Cancer medicine · 2018Article
- Biliary tract cancer stem cells - translational options and challenges.World journal of gastroenterology · 2017Review
- The Role of Cancer-Associated Fibroblasts and Fibrosis in Liver Cancer.Annual review of pathology · 2017Review
- Hedgehog signaling pathway in colorectal cancer: function, mechanism, and therapy.OncoTargets and therapy · 2017Review
- Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (CCA) are the two most common primary liver malignancies in adult patients. The molecular mechanisms underlying the pathogenesis of HCC and CCA are still poorly understood. Sonic hedgehog (SHH) signaling plays an essential role during mammalian development, i.e., promoting organ growth, tissue differentiation, and cell polarity. The upregulation of SHH has been observed during carcinogenesis, including colorectal carcinoma. Our aim was to investigate the expression pattern of SHH in HCC and CCA. We investigated 40 malignant tumors of the liver, including 21 HCC and 19 of intrahepatic CCA cases by immunohistochemistry (IHC) using a polyclonal antibody against SHH and Avidin-Biotin Complex method. We also investigated the co-localization of SHH and Bone morphogenetic protein 4 (BMP4) in CCA using indirect double IHC. Moreover, we examined whether SHH is expressed in two HCC cell lines HepG2 and HuH-7 and three CCA cell lines OZ, HuCCT1 and HuH28. We found that SHH was expressed in 15 out of 21 cases (71.4 %) of HCC and 100 % of CCA cases by immunohistochemistry. SHH expression showed a positive trend in liver tumors (HCC, CCA) with high grade (G2-G3). SHH localized to the epithelial cells, while BMP4 was expressed in the stromal cells in CCA by double IHC. However, both HCC and CCA cell lines showed SHH expression by Western blot analysis. In conclusion, SHH seems to be an interesting marker of de-differentiation in liver tumors and the simultaneous epithelial-mesenchymal expression may be an intriguing prompt to investigate cross-talks between SHH and BMP4.
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