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Prognostic Value of Complement Properdin in Cancer

The complement system is readily triggered by the presence of damage-associated molecular patterns on the surface of tumor cells. The complement alternative pathway provides rapid amplification of the molecular stress signal, leading to complement cascade activation to deal with pathogens or maligna...

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Autores principales: Mangogna, Alessandro, Varghese, Praveen M., Agostinis, Chiara, Alrokayan, Salman H., Khan, Haseeb A., Stover, Cordula M., Belmonte, Beatrice, Martorana, Anna, Ricci, Giuseppe, Bulla, Roberta, Kishore, Uday
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7851055/
https://www.ncbi.nlm.nih.gov/pubmed/33542722
http://dx.doi.org/10.3389/fimmu.2020.614980
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author Mangogna, Alessandro
Varghese, Praveen M.
Agostinis, Chiara
Alrokayan, Salman H.
Khan, Haseeb A.
Stover, Cordula M.
Belmonte, Beatrice
Martorana, Anna
Ricci, Giuseppe
Bulla, Roberta
Kishore, Uday
author_facet Mangogna, Alessandro
Varghese, Praveen M.
Agostinis, Chiara
Alrokayan, Salman H.
Khan, Haseeb A.
Stover, Cordula M.
Belmonte, Beatrice
Martorana, Anna
Ricci, Giuseppe
Bulla, Roberta
Kishore, Uday
author_sort Mangogna, Alessandro
collection PubMed
description The complement system is readily triggered by the presence of damage-associated molecular patterns on the surface of tumor cells. The complement alternative pathway provides rapid amplification of the molecular stress signal, leading to complement cascade activation to deal with pathogens or malignant cells. Properdin is the only known positive regulator of the alternative pathway. In addition, properdin promotes the phagocytic uptake of apoptotic T cells by macrophages and dendritic cells without activating the complement system, thus, establishing its ability to recognize “altered-self”. Dysregulation of properdin has been implicated in substantial tissue damage in the host, and in some cases, chronic unresolved inflammation. A corollary of this may be the development of cancer. Hence, to establish a correlation between properdin presence/levels in normal and cancer tissues, we performed bioinformatics analysis, using Oncomine and UALCAN. Survival analyses were performed using UALCAN and PROGgeneV2 to assess if properdin can serve as a potential prognostic marker for human lung adenocarcinoma (LUAD), liver hepatocellular carcinoma (LIHC), cervical squamous cell carcinoma (CESC), and pancreatic adenocarcinoma (PAAD). We also analyzed levels of tumor-infiltrating immune cells using TIMER, a tool for characterizing immune cell composition in cancers. We found that in LUAD and LIHC, there was a lower expression of properdin in the tumors compared to normal tissues, while no significant difference was observed in CESC and PAAD. Survival analysis demonstrated a positive association between properdin mRNA expression and overall survival in all 4 types of cancers. TIMER analysis revealed that properdin expression correlated negatively with tumor purity and positively with levels of infiltrating B cells, cytotoxic CD8(+) T cells, CD4(+) helper T cells, macrophages, neutrophils and dendritic cells in LUAD, CESC and PAAD, and with levels of B cells, CD8(+) T cells and dendritic cells in LIHC. Immunohistochemical analysis revealed that infiltrating immune cells were the most likely source of properdin in the tumor microenvironment. Thus, complement protein properdin shows promise as a prognostic marker in cancer and warrants further study.
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spelling pubmed-78510552021-02-03 Prognostic Value of Complement Properdin in Cancer Mangogna, Alessandro Varghese, Praveen M. Agostinis, Chiara Alrokayan, Salman H. Khan, Haseeb A. Stover, Cordula M. Belmonte, Beatrice Martorana, Anna Ricci, Giuseppe Bulla, Roberta Kishore, Uday Front Immunol Immunology The complement system is readily triggered by the presence of damage-associated molecular patterns on the surface of tumor cells. The complement alternative pathway provides rapid amplification of the molecular stress signal, leading to complement cascade activation to deal with pathogens or malignant cells. Properdin is the only known positive regulator of the alternative pathway. In addition, properdin promotes the phagocytic uptake of apoptotic T cells by macrophages and dendritic cells without activating the complement system, thus, establishing its ability to recognize “altered-self”. Dysregulation of properdin has been implicated in substantial tissue damage in the host, and in some cases, chronic unresolved inflammation. A corollary of this may be the development of cancer. Hence, to establish a correlation between properdin presence/levels in normal and cancer tissues, we performed bioinformatics analysis, using Oncomine and UALCAN. Survival analyses were performed using UALCAN and PROGgeneV2 to assess if properdin can serve as a potential prognostic marker for human lung adenocarcinoma (LUAD), liver hepatocellular carcinoma (LIHC), cervical squamous cell carcinoma (CESC), and pancreatic adenocarcinoma (PAAD). We also analyzed levels of tumor-infiltrating immune cells using TIMER, a tool for characterizing immune cell composition in cancers. We found that in LUAD and LIHC, there was a lower expression of properdin in the tumors compared to normal tissues, while no significant difference was observed in CESC and PAAD. Survival analysis demonstrated a positive association between properdin mRNA expression and overall survival in all 4 types of cancers. TIMER analysis revealed that properdin expression correlated negatively with tumor purity and positively with levels of infiltrating B cells, cytotoxic CD8(+) T cells, CD4(+) helper T cells, macrophages, neutrophils and dendritic cells in LUAD, CESC and PAAD, and with levels of B cells, CD8(+) T cells and dendritic cells in LIHC. Immunohistochemical analysis revealed that infiltrating immune cells were the most likely source of properdin in the tumor microenvironment. Thus, complement protein properdin shows promise as a prognostic marker in cancer and warrants further study. Frontiers Media S.A. 2021-01-19 /pmc/articles/PMC7851055/ /pubmed/33542722 http://dx.doi.org/10.3389/fimmu.2020.614980 Text en Copyright © 2021 Mangogna, Varghese, Agostinis, Alrokayan, Khan, Stover, Belmonte, Martorana, Ricci, Bulla and Kishore http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Mangogna, Alessandro
Varghese, Praveen M.
Agostinis, Chiara
Alrokayan, Salman H.
Khan, Haseeb A.
Stover, Cordula M.
Belmonte, Beatrice
Martorana, Anna
Ricci, Giuseppe
Bulla, Roberta
Kishore, Uday
Prognostic Value of Complement Properdin in Cancer
title Prognostic Value of Complement Properdin in Cancer
title_full Prognostic Value of Complement Properdin in Cancer
title_fullStr Prognostic Value of Complement Properdin in Cancer
title_full_unstemmed Prognostic Value of Complement Properdin in Cancer
title_short Prognostic Value of Complement Properdin in Cancer
title_sort prognostic value of complement properdin in cancer
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7851055/
https://www.ncbi.nlm.nih.gov/pubmed/33542722
http://dx.doi.org/10.3389/fimmu.2020.614980
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