Hedgehog components are overexpressed in a series of liver cancer cases.

Autor: Sales CBS; Department of Biomorphology, Institute of Health Sciences, Federal University of Bahia (UFBA), Salvador, Bahia, 40110-902, Brazil., Dias RB; Gonçalo Moniz Institute, Oswaldo Cruz Foundation (IGM-FIOCRUZ/BA), Salvador, Bahia, 40296-710, Brazil.; Department of Propedeutics, School of Dentistry of the Federal University of Bahia (UFBA), Salvador, Bahia, 40110-909, Brazil.; Department of Biological Sciences, State University of Feira de Santana (UEFS), Feira de Santana, Bahia, 44036-900, Brazil., de Faro Valverde L; Gonçalo Moniz Institute, Oswaldo Cruz Foundation (IGM-FIOCRUZ/BA), Salvador, Bahia, 40296-710, Brazil.; Department of Dentistry, Federal University of Sergipe (UFS), Lagarto, Sergipe, 49400-000, Brazil., Bomfim LM; Gonçalo Moniz Institute, Oswaldo Cruz Foundation (IGM-FIOCRUZ/BA), Salvador, Bahia, 40296-710, Brazil., Silva LA; Gonçalo Moniz Institute, Oswaldo Cruz Foundation (IGM-FIOCRUZ/BA), Salvador, Bahia, 40296-710, Brazil., de Carvalho NC; Gonçalo Moniz Institute, Oswaldo Cruz Foundation (IGM-FIOCRUZ/BA), Salvador, Bahia, 40296-710, Brazil., Bastos JLA; Medical School of Bahia, Federal University of Bahia (UFBA), Salvador, Bahia, 40110-100, Brazil., Tilli TM; Translational Oncology Platform, Center for Technological Development in Health, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Rio de Janeiro, 21040-900, Brazil.; Laboratory of Cardiovascular Research, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Rio de Janeiro, 21040-900, Brazil., Rocha GV; Gonçalo Moniz Institute, Oswaldo Cruz Foundation (IGM-FIOCRUZ/BA), Salvador, Bahia, 40296-710, Brazil.; D'Or Institute for Research and Education (IDOR), São Rafael Hospital Center for Biotechnology and Cell Therapy, Salvador, Bahia, 41650-010, Brazil., Soares MBP; Gonçalo Moniz Institute, Oswaldo Cruz Foundation (IGM-FIOCRUZ/BA), Salvador, Bahia, 40296-710, Brazil. milena.soares@fiocruz.br.; SENAI Institute for Innovation in Advanced Health Systems, SENAI CIMATEC, Salvador, Bahia, 41650-010, Brazil. milena.soares@fiocruz.br., de Freitas LAR; Gonçalo Moniz Institute, Oswaldo Cruz Foundation (IGM-FIOCRUZ/BA), Salvador, Bahia, 40296-710, Brazil. freitas.luizar@gmail.com.; Medical School of Bahia, Federal University of Bahia (UFBA), Salvador, Bahia, 40110-100, Brazil. freitas.luizar@gmail.com., Gurgel Rocha CA; Gonçalo Moniz Institute, Oswaldo Cruz Foundation (IGM-FIOCRUZ/BA), Salvador, Bahia, 40296-710, Brazil. clarissa.gurgel@fiocruz.br.; Department of Propedeutics, School of Dentistry of the Federal University of Bahia (UFBA), Salvador, Bahia, 40110-909, Brazil. clarissa.gurgel@fiocruz.br.; D'Or Institute for Research and Education (IDOR), São Rafael Hospital Center for Biotechnology and Cell Therapy, Salvador, Bahia, 41650-010, Brazil. clarissa.gurgel@fiocruz.br., Bezerra DP; Gonçalo Moniz Institute, Oswaldo Cruz Foundation (IGM-FIOCRUZ/BA), Salvador, Bahia, 40296-710, Brazil. daniel.bezerra@fiocruz.br.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2024 Aug 22; Vol. 14 (1), pp. 19507. Date of Electronic Publication: 2024 Aug 22.
DOI: 10.1038/s41598-024-70220-0
Abstrakt: Liver cancers, including hepatocellular carcinoma (HCC), are the sixth most common cancer and the third leading cause of cancer-related death worldwide, representing a global public health problem. This study evaluated nine patients with HCC. Six of the cases involved hepatic explants, and three involved hepatic segmentectomy for tumor resection. Eight out of nine tumors were HCC, with one being a combined hepatocellular-cholangiocarcinoma tumor. Conventional markers of hepatocellular differentiation (Hep Par-1, arginase, pCEA, and glutamine synthetase) were positive in all patients, while markers of hepatic precursor cells (CK19, CK7, EpCAM, and CD56) were negative in most patients, and when positive, they were detected in small, isolated foci. Based on in silico analysis of HCC tumors from The Cancer Genome Atlas database, we found that Hedgehog (HH) pathway components (GLI1, GLI2, GLI3 and GAS1) have high connectivity values (module membership > 0.7) and are strongly correlated with each other and with other genes in biologically relevant modules for HCC. We further validated this finding by analyzing the gene expression of HH components (PTCH1, GLI1, GLI2 and GLI3) in our samples through qPCR, as well as by immunohistochemical analysis. Additionally, we conducted a chemosensitivity analysis using primary HCC cultures treated with a panel of 18 drugs that affect the HH pathway and/or HCC. Most HCC samples were sensitive to sunitinib. Our results offer a comprehensive view of the molecular landscape of HCC, highlighting the significance of the HH pathway and providing insight into focused treatments for HCC.
(© 2024. The Author(s).)
Databáze: MEDLINE
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