sHLA-G as a biomarker for colorectal cancer pathogenesis

Objectives: Colorectal cancer (CRC) is a serious gastrointestinal disease. Cancer cells can survive in a microenvironment that includes distinct immune cells, various immune checkpoints including HLA-G, and different immune effectors such as interleukin-6 (IL-6), TNF-alpha (TNF-α), and interferon-ga...

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Autores principales:	Sabrine Dhouioui, Nadia Boujelbene, Hanen Chelbi, Ines Zemni, Ines Ben Safta, Hadda-Imene Ouzari, Amel Mezlini, Abdel Halim Harrath, Vera Rebmann, Inès Zidi
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2022
Materias:	Colorectal cancer sHLA-G Extracellular vesicles Cytokines T lymphocytes Science (General) Q1-390
Acceso en línea:	https://doaj.org/article/e1e037c8ecbf48bfba706e45f9e7065c
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spelling	oai:doaj.org-article:e1e037c8ecbf48bfba706e45f9e7065c2021-12-02T04:59:30ZsHLA-G as a biomarker for colorectal cancer pathogenesis1018-364710.1016/j.jksus.2021.101708https://doaj.org/article/e1e037c8ecbf48bfba706e45f9e7065c2022-01-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S1018364721003700https://doaj.org/toc/1018-3647Objectives: Colorectal cancer (CRC) is a serious gastrointestinal disease. Cancer cells can survive in a microenvironment that includes distinct immune cells, various immune checkpoints including HLA-G, and different immune effectors such as interleukin-6 (IL-6), TNF-alpha (TNF-α), and interferon-gamma (IFN-γ). Thus, the objective of this study was to investigate HLA-G involvement in CRC as a prognostic factor in the Tunisian population, both in its soluble form (sHLA-G) and in its form linked to extracellular vesicles (HLA-GEV). Additionally, we examined its association to the secretion of cytokines. Methods: Fifty Tunisian patients, diagnosed with CRC, matched with ninety-eight healthy blood donors (HD) were enrolled in this study. Levels of sHLA-G, HLA-GEV, IL-6, TNF-α, and IFN-γ were dosed in plasma samples using specific ELISA. For the functional assay, we assessed sHLA-G effects on the production of cytokines by stimulated T lymphocytes. We measured the concentration of IL-6, TNF-α, and IFN-γ produced by activated T lymphocytes pre-stimulated by plasma sHLA-G and HLA-GEV. Results: Our case-control analysis showed high concentration of both sHLA-G (8.8 [0–63] ng/ml vs. 2.1 [0–63] ng/ml, p < 0.0001) and HLA-GEV (0.9 [0–17.8] ng/ml vs. 0.3 [0–31.0] ng/ml, p = 0.018) in CRC patients compared to HD. Concerning cytokines, IL-6 exclusively increased compared to HD (7.1[0.0–104.0] pg/ml vs. 3.6[0.0–58.22] pg/ml, p = 0.005). The evaluation of diagnostic performance using the receiver operating characteristic (ROC) curves and the area under the curve (AUC) showed sHLA-G (AUC = 0.828) as the more adequate biomarker in colorectal carcinoma prediction compared to HLA-GEV (AUC = 0.615) and IL-6 (AUC = 0.664). We found that sHLA-G is able to decrease IL-6, TNF-α, and IFN-γ production by stimulated T lymphocytes in a concentration-independent manner. Additionally, HLA-GEV appears to downregulate solely IL-6 release by stimulated T lymphocytes. Interestingly, HLA-GEV was related to lymph node infiltration, which represents the most common metastatic route for colorectal cancer via the lymphatic system. Conclusions: We outlined the importance of sHLA-G and HLA-GEV as substantial immune biomarkers in CRC. Our findings suggest that HLA-G could be an effective diagnostic tool for colorectal cancer.Sabrine DhouiouiNadia BoujelbeneHanen ChelbiInes ZemniInes Ben SaftaHadda-Imene OuzariAmel MezliniAbdel Halim HarrathVera RebmannInès ZidiElsevierarticleColorectal cancersHLA-GExtracellular vesiclesCytokinesT lymphocytesScience (General)Q1-390ENJournal of King Saud University: Science, Vol 34, Iss 1, Pp 101708- (2022)
institution	DOAJ
collection	DOAJ
language	EN
topic	Colorectal cancer sHLA-G Extracellular vesicles Cytokines T lymphocytes Science (General) Q1-390
spellingShingle	Colorectal cancer sHLA-G Extracellular vesicles Cytokines T lymphocytes Science (General) Q1-390 Sabrine Dhouioui Nadia Boujelbene Hanen Chelbi Ines Zemni Ines Ben Safta Hadda-Imene Ouzari Amel Mezlini Abdel Halim Harrath Vera Rebmann Inès Zidi sHLA-G as a biomarker for colorectal cancer pathogenesis
description	Objectives: Colorectal cancer (CRC) is a serious gastrointestinal disease. Cancer cells can survive in a microenvironment that includes distinct immune cells, various immune checkpoints including HLA-G, and different immune effectors such as interleukin-6 (IL-6), TNF-alpha (TNF-α), and interferon-gamma (IFN-γ). Thus, the objective of this study was to investigate HLA-G involvement in CRC as a prognostic factor in the Tunisian population, both in its soluble form (sHLA-G) and in its form linked to extracellular vesicles (HLA-GEV). Additionally, we examined its association to the secretion of cytokines. Methods: Fifty Tunisian patients, diagnosed with CRC, matched with ninety-eight healthy blood donors (HD) were enrolled in this study. Levels of sHLA-G, HLA-GEV, IL-6, TNF-α, and IFN-γ were dosed in plasma samples using specific ELISA. For the functional assay, we assessed sHLA-G effects on the production of cytokines by stimulated T lymphocytes. We measured the concentration of IL-6, TNF-α, and IFN-γ produced by activated T lymphocytes pre-stimulated by plasma sHLA-G and HLA-GEV. Results: Our case-control analysis showed high concentration of both sHLA-G (8.8 [0–63] ng/ml vs. 2.1 [0–63] ng/ml, p < 0.0001) and HLA-GEV (0.9 [0–17.8] ng/ml vs. 0.3 [0–31.0] ng/ml, p = 0.018) in CRC patients compared to HD. Concerning cytokines, IL-6 exclusively increased compared to HD (7.1[0.0–104.0] pg/ml vs. 3.6[0.0–58.22] pg/ml, p = 0.005). The evaluation of diagnostic performance using the receiver operating characteristic (ROC) curves and the area under the curve (AUC) showed sHLA-G (AUC = 0.828) as the more adequate biomarker in colorectal carcinoma prediction compared to HLA-GEV (AUC = 0.615) and IL-6 (AUC = 0.664). We found that sHLA-G is able to decrease IL-6, TNF-α, and IFN-γ production by stimulated T lymphocytes in a concentration-independent manner. Additionally, HLA-GEV appears to downregulate solely IL-6 release by stimulated T lymphocytes. Interestingly, HLA-GEV was related to lymph node infiltration, which represents the most common metastatic route for colorectal cancer via the lymphatic system. Conclusions: We outlined the importance of sHLA-G and HLA-GEV as substantial immune biomarkers in CRC. Our findings suggest that HLA-G could be an effective diagnostic tool for colorectal cancer.
format	article
author	Sabrine Dhouioui Nadia Boujelbene Hanen Chelbi Ines Zemni Ines Ben Safta Hadda-Imene Ouzari Amel Mezlini Abdel Halim Harrath Vera Rebmann Inès Zidi
author_facet	Sabrine Dhouioui Nadia Boujelbene Hanen Chelbi Ines Zemni Ines Ben Safta Hadda-Imene Ouzari Amel Mezlini Abdel Halim Harrath Vera Rebmann Inès Zidi
author_sort	Sabrine Dhouioui
title	sHLA-G as a biomarker for colorectal cancer pathogenesis
title_short	sHLA-G as a biomarker for colorectal cancer pathogenesis
title_full	sHLA-G as a biomarker for colorectal cancer pathogenesis
title_fullStr	sHLA-G as a biomarker for colorectal cancer pathogenesis
title_full_unstemmed	sHLA-G as a biomarker for colorectal cancer pathogenesis
title_sort	shla-g as a biomarker for colorectal cancer pathogenesis
publisher	Elsevier
publishDate	2022
url	https://doaj.org/article/e1e037c8ecbf48bfba706e45f9e7065c
work_keys_str_mv	AT sabrinedhouioui shlagasabiomarkerforcolorectalcancerpathogenesis AT nadiaboujelbene shlagasabiomarkerforcolorectalcancerpathogenesis AT hanenchelbi shlagasabiomarkerforcolorectalcancerpathogenesis AT ineszemni shlagasabiomarkerforcolorectalcancerpathogenesis AT inesbensafta shlagasabiomarkerforcolorectalcancerpathogenesis AT haddaimeneouzari shlagasabiomarkerforcolorectalcancerpathogenesis AT amelmezlini shlagasabiomarkerforcolorectalcancerpathogenesis AT abdelhalimharrath shlagasabiomarkerforcolorectalcancerpathogenesis AT verarebmann shlagasabiomarkerforcolorectalcancerpathogenesis AT ineszidi shlagasabiomarkerforcolorectalcancerpathogenesis
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sHLA-G as a biomarker for colorectal cancer pathogenesis

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