Elevated soluble TNFα levels and upregulated TNFα mRNA expression in purified peripheral blood monocyte subsets associated with high-grade hepatocellular carcinoma
Abstract Background Chronic inflammation is involved in the initiation and progression of various cancers, including liver cancer. The current study focuses on the characterization of the peripheral immune response in hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) patients, before and a...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2020-03-01
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| Series: | Journal of Inflammation |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12950-020-00243-7 |
| _version_ | 1828775760038461440 |
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| author | C. Martín-Sierra R. Martins M. Coucelo A. M. Abrantes R. C. Oliveira J. G. Tralhão M. F. Botelho E. Furtado M. R. Domingues A. Paiva P. Laranjeira |
| author_facet | C. Martín-Sierra R. Martins M. Coucelo A. M. Abrantes R. C. Oliveira J. G. Tralhão M. F. Botelho E. Furtado M. R. Domingues A. Paiva P. Laranjeira |
| author_sort | C. Martín-Sierra |
| collection | DOAJ |
| description | Abstract Background Chronic inflammation is involved in the initiation and progression of various cancers, including liver cancer. The current study focuses on the characterization of the peripheral immune response in hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) patients, before and after surgical procedure, in order to assess the effect of tumor resection in the immune system homeostasis and to determine possible prognostic factors associated with high-grade tumors. We developed a whole-blood assay to monitor immune alterations and functional competence of peripheral monocytes in a group of 10 healthy individuals (HG), in 20 HCC patients and 8 CCA patients, by multi-color flow cytometry, qRT-PCR, and ELISA techniques. Results The qRT-PCR analysis showed an upregulation of TNFα expression by classical and intermediate monocytes purified from HCC patients presenting tumors in grade G3-G4 as compared to G1-G2 HCC patients. Moreover, ELISA assay confirmed elevated serum levels of TNFα in G3-G4 compared to G1-G2 HCC patients. A significant decrease of circulating non-classical monocytes was detected in both CCA and HCC patients before and after surgical procedure. In addition, a functional defect in circulating classical and intermediate monocytes was observed in both groups of cancer patients when compared to the HG, with partial recovery after the surgical intervention. Conclusions This integrated analysis permitted the identification of altered functional competence of monocyte subsets in CCA and HCC patients. In addition, our results point to a potential role of TNFα as a prognostic peripheral biomarker in HCC patients, indicating the presence of high-grade tumors that should be further validated. |
| first_indexed | 2024-12-11T15:46:06Z |
| format | Article |
| id | doaj.art-e7a01e01a25148799ea2434cca8f361e |
| institution | Directory Open Access Journal |
| issn | 1476-9255 |
| language | English |
| last_indexed | 2024-12-11T15:46:06Z |
| publishDate | 2020-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Inflammation |
| spelling | doaj.art-e7a01e01a25148799ea2434cca8f361e2022-12-22T00:59:41ZengBMCJournal of Inflammation1476-92552020-03-0117111110.1186/s12950-020-00243-7Elevated soluble TNFα levels and upregulated TNFα mRNA expression in purified peripheral blood monocyte subsets associated with high-grade hepatocellular carcinomaC. Martín-Sierra0R. Martins1M. Coucelo2A. M. Abrantes3R. C. Oliveira4J. G. Tralhão5M. F. Botelho6E. Furtado7M. R. Domingues8A. Paiva9P. Laranjeira10Flow Cytometry Unit, Clinical Pathology Service, Centro Hospitalar e Universitário de CoimbraUnidade Transplantação Hepática Pediátrica e de Adultos, Centro Hospitalar e Universitário de Coimbra (UTHPA, CHUC)Unidade de Hematologia Molecular, Serviço de Hematologia Clínica, Centro Hospitalar e Universitário de Coimbra (CHUC)Instituto de Biofísica, IBILI, Faculdade de Medicina, Universidade de CoimbraInstituto de Biofísica, IBILI, Faculdade de Medicina, Universidade de CoimbraUnidade Transplantação Hepática Pediátrica e de Adultos, Centro Hospitalar e Universitário de Coimbra (UTHPA, CHUC)Instituto de Biofísica, IBILI, Faculdade de Medicina, Universidade de CoimbraUnidade Transplantação Hepática Pediátrica e de Adultos, Centro Hospitalar e Universitário de Coimbra (UTHPA, CHUC)Mass Spectrometry Centre, Department of Chemistry & QOPNA, University of Aveiro, Campus Universitário de SantiagoFlow Cytometry Unit, Clinical Pathology Service, Centro Hospitalar e Universitário de CoimbraFlow Cytometry Unit, Clinical Pathology Service, Centro Hospitalar e Universitário de CoimbraAbstract Background Chronic inflammation is involved in the initiation and progression of various cancers, including liver cancer. The current study focuses on the characterization of the peripheral immune response in hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) patients, before and after surgical procedure, in order to assess the effect of tumor resection in the immune system homeostasis and to determine possible prognostic factors associated with high-grade tumors. We developed a whole-blood assay to monitor immune alterations and functional competence of peripheral monocytes in a group of 10 healthy individuals (HG), in 20 HCC patients and 8 CCA patients, by multi-color flow cytometry, qRT-PCR, and ELISA techniques. Results The qRT-PCR analysis showed an upregulation of TNFα expression by classical and intermediate monocytes purified from HCC patients presenting tumors in grade G3-G4 as compared to G1-G2 HCC patients. Moreover, ELISA assay confirmed elevated serum levels of TNFα in G3-G4 compared to G1-G2 HCC patients. A significant decrease of circulating non-classical monocytes was detected in both CCA and HCC patients before and after surgical procedure. In addition, a functional defect in circulating classical and intermediate monocytes was observed in both groups of cancer patients when compared to the HG, with partial recovery after the surgical intervention. Conclusions This integrated analysis permitted the identification of altered functional competence of monocyte subsets in CCA and HCC patients. In addition, our results point to a potential role of TNFα as a prognostic peripheral biomarker in HCC patients, indicating the presence of high-grade tumors that should be further validated.http://link.springer.com/article/10.1186/s12950-020-00243-7Flow cytometryqRT-PCRHepatocellular carcinomaCholangiocarcinomaCirculating monocytesTNFα |
| spellingShingle | C. Martín-Sierra R. Martins M. Coucelo A. M. Abrantes R. C. Oliveira J. G. Tralhão M. F. Botelho E. Furtado M. R. Domingues A. Paiva P. Laranjeira Elevated soluble TNFα levels and upregulated TNFα mRNA expression in purified peripheral blood monocyte subsets associated with high-grade hepatocellular carcinoma Journal of Inflammation Flow cytometry qRT-PCR Hepatocellular carcinoma Cholangiocarcinoma Circulating monocytes TNFα |
| title | Elevated soluble TNFα levels and upregulated TNFα mRNA expression in purified peripheral blood monocyte subsets associated with high-grade hepatocellular carcinoma |
| title_full | Elevated soluble TNFα levels and upregulated TNFα mRNA expression in purified peripheral blood monocyte subsets associated with high-grade hepatocellular carcinoma |
| title_fullStr | Elevated soluble TNFα levels and upregulated TNFα mRNA expression in purified peripheral blood monocyte subsets associated with high-grade hepatocellular carcinoma |
| title_full_unstemmed | Elevated soluble TNFα levels and upregulated TNFα mRNA expression in purified peripheral blood monocyte subsets associated with high-grade hepatocellular carcinoma |
| title_short | Elevated soluble TNFα levels and upregulated TNFα mRNA expression in purified peripheral blood monocyte subsets associated with high-grade hepatocellular carcinoma |
| title_sort | elevated soluble tnfα levels and upregulated tnfα mrna expression in purified peripheral blood monocyte subsets associated with high grade hepatocellular carcinoma |
| topic | Flow cytometry qRT-PCR Hepatocellular carcinoma Cholangiocarcinoma Circulating monocytes TNFα |
| url | http://link.springer.com/article/10.1186/s12950-020-00243-7 |
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