PMID- 32256215 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20231113 IS - 1476-9255 (Print) IS - 1476-9255 (Electronic) IS - 1476-9255 (Linking) VI - 17 DP - 2020 TI - Elevated soluble TNFalpha levels and upregulated TNFalpha mRNA expression in purified peripheral blood monocyte subsets associated with high-grade hepatocellular carcinoma. PG - 14 LID - 10.1186/s12950-020-00243-7 [doi] LID - 14 AB - 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 TNFalpha 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 TNFalpha 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 TNFalpha as a prognostic peripheral biomarker in HCC patients, indicating the presence of high-grade tumors that should be further validated. CI - (c) The Author(s) 2020. FAU - Martin-Sierra, C AU - Martin-Sierra C AUID- ORCID: 0000-0001-5120-1054 AD - 1Flow Cytometry Unit, Clinical Pathology Service, Centro Hospitalar e Universitario de Coimbra, Praceta Prof. Mota Pinto, Ed. S. Jeronimo, 3 degrees piso, Coimbra, Portugal. GRID: grid.28911.33. ISNI: 0000000106861985 AD - 2Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, Coimbra, Portugal. GRID: grid.8051.c. ISNI: 0000 0000 9511 4342 AD - 3Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, Coimbra, Portugal. GRID: grid.8051.c. ISNI: 0000 0000 9511 4342 FAU - Martins, R AU - Martins R AD - 4Unidade Transplantacao Hepatica Pediatrica e de Adultos, Centro Hospitalar e Universitario de Coimbra (UTHPA, CHUC), Coimbra, Portugal. GRID: grid.28911.33. ISNI: 0000000106861985 AD - 5Servico de Cirurgia Geral, Unidade HBP, Centro Hospitalar e Universitario de Coimbra (CHUC), Coimbra, Portugal. GRID: grid.28911.33. ISNI: 0000000106861985 AD - 6Instituto de Biofisica, IBILI, Faculdade de Medicina, Universidade de Coimbra, Coimbra, Portugal. GRID: grid.8051.c. ISNI: 0000 0000 9511 4342 AD - 7Coimbra Institute for Clinical and Biomedical Research (iCBR) area of Environment Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, Coimbra, Portugal. GRID: grid.8051.c. ISNI: 0000 0000 9511 4342 FAU - Coucelo, M AU - Coucelo M AD - 8Unidade de Hematologia Molecular, Servico de Hematologia Clinica, Centro Hospitalar e Universitario de Coimbra (CHUC), Coimbra, Portugal. GRID: grid.28911.33. ISNI: 0000000106861985 FAU - Abrantes, A M AU - Abrantes AM AD - 6Instituto de Biofisica, IBILI, Faculdade de Medicina, Universidade de Coimbra, Coimbra, Portugal. GRID: grid.8051.c. ISNI: 0000 0000 9511 4342 AD - 7Coimbra Institute for Clinical and Biomedical Research (iCBR) area of Environment Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, Coimbra, Portugal. GRID: grid.8051.c. ISNI: 0000 0000 9511 4342 FAU - Oliveira, R C AU - Oliveira RC AD - 6Instituto de Biofisica, IBILI, Faculdade de Medicina, Universidade de Coimbra, Coimbra, Portugal. GRID: grid.8051.c. ISNI: 0000 0000 9511 4342 AD - 7Coimbra Institute for Clinical and Biomedical Research (iCBR) area of Environment Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, Coimbra, Portugal. GRID: grid.8051.c. ISNI: 0000 0000 9511 4342 AD - 9Servico de Anatomia Patologica, Centro Hospitalar e Universitario de Coimbra (CHUC), Coimbra, Portugal. GRID: grid.28911.33. ISNI: 0000000106861985 FAU - Tralhao, J G AU - Tralhao JG AD - 4Unidade Transplantacao Hepatica Pediatrica e de Adultos, Centro Hospitalar e Universitario de Coimbra (UTHPA, CHUC), Coimbra, Portugal. GRID: grid.28911.33. ISNI: 0000000106861985 AD - 5Servico de Cirurgia Geral, Unidade HBP, Centro Hospitalar e Universitario de Coimbra (CHUC), Coimbra, Portugal. GRID: grid.28911.33. ISNI: 0000000106861985 AD - 6Instituto de Biofisica, IBILI, Faculdade de Medicina, Universidade de Coimbra, Coimbra, Portugal. GRID: grid.8051.c. ISNI: 0000 0000 9511 4342 AD - 7Coimbra Institute for Clinical and Biomedical Research (iCBR) area of Environment Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, Coimbra, Portugal. GRID: grid.8051.c. ISNI: 0000 0000 9511 4342 FAU - Botelho, M F AU - Botelho MF AD - 6Instituto de Biofisica, IBILI, Faculdade de Medicina, Universidade de Coimbra, Coimbra, Portugal. GRID: grid.8051.c. ISNI: 0000 0000 9511 4342 AD - 7Coimbra Institute for Clinical and Biomedical Research (iCBR) area of Environment Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, Coimbra, Portugal. GRID: grid.8051.c. ISNI: 0000 0000 9511 4342 FAU - Furtado, E AU - Furtado E AD - 4Unidade Transplantacao Hepatica Pediatrica e de Adultos, Centro Hospitalar e Universitario de Coimbra (UTHPA, CHUC), Coimbra, Portugal. GRID: grid.28911.33. ISNI: 0000000106861985 FAU - Domingues, M R AU - Domingues MR AD - 10Mass Spectrometry Centre, Department of Chemistry & QOPNA, University of Aveiro, Campus Universitario de Santiago, Aveiro, Portugal. GRID: grid.7311.4. ISNI: 0000000123236065 FAU - Paiva, A AU - Paiva A AUID- ORCID: 0000-0002-6562-5859 AD - 1Flow Cytometry Unit, Clinical Pathology Service, Centro Hospitalar e Universitario de Coimbra, Praceta Prof. Mota Pinto, Ed. S. Jeronimo, 3 degrees piso, Coimbra, Portugal. GRID: grid.28911.33. ISNI: 0000000106861985 AD - 2Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, Coimbra, Portugal. GRID: grid.8051.c. ISNI: 0000 0000 9511 4342 AD - 3Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, Coimbra, Portugal. GRID: grid.8051.c. ISNI: 0000 0000 9511 4342 AD - 11Instituto Politecnico de Coimbra, ESTESC-Coimbra Health School, Ciencias Biomedicas Laboratoriais, Coimbra, Portugal. GRID: grid.88832.39. ISNI: 0000 0001 2289 6301 FAU - Laranjeira, P AU - Laranjeira P AD - 1Flow Cytometry Unit, Clinical Pathology Service, Centro Hospitalar e Universitario de Coimbra, Praceta Prof. Mota Pinto, Ed. S. Jeronimo, 3 degrees piso, Coimbra, Portugal. GRID: grid.28911.33. ISNI: 0000000106861985 AD - 2Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, Coimbra, Portugal. GRID: grid.8051.c. ISNI: 0000 0000 9511 4342 AD - 3Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, Coimbra, Portugal. GRID: grid.8051.c. ISNI: 0000 0000 9511 4342 LA - eng PT - Journal Article DEP - 20200330 PL - England TA - J Inflamm (Lond) JT - Journal of inflammation (London, England) JID - 101232234 PMC - PMC7106708 OTO - NOTNLM OT - Cholangiocarcinoma OT - Circulating monocytes OT - Flow cytometry OT - Hepatocellular carcinoma OT - TNFalpha OT - qRT-PCR COIS- Competing interestsThe authors declare that they have no competing interests. EDAT- 2020/04/08 06:00 MHDA- 2020/04/08 06:01 PMCR- 2020/03/30 CRDT- 2020/04/08 06:00 PHST- 2019/12/13 00:00 [received] PHST- 2020/03/13 00:00 [accepted] PHST- 2020/04/08 06:00 [entrez] PHST- 2020/04/08 06:00 [pubmed] PHST- 2020/04/08 06:01 [medline] PHST- 2020/03/30 00:00 [pmc-release] AID - 243 [pii] AID - 10.1186/s12950-020-00243-7 [doi] PST - epublish SO - J Inflamm (Lond). 2020 Mar 30;17:14. doi: 10.1186/s12950-020-00243-7. eCollection 2020.