evaluation-interplay-between-complement-protein-c1q-hyaluronic-acid

Evaluation of the Interplay Between the Complement Protein C1q and Hyaluronic Acid in Promoting Cell Adhesion

It has been increasingly demonstrated that the tumor microenvironment plays an active role in neoplasia growth and metastasis. Through different pathways, ...

University of Trieste

In pregnancy, excessive inflammation and break down of immunologic tolerance can contribute to miscarriage. Endothelial cells (ECs) are able to orchestrate the inflammatory processes by secreting pro-inflammatory mediators and bactericidal factors by modulating leakiness and leukocyte trafficking, via the expression of adhesion molecules and chemokines. The aim of this study was to analyse the differences in the phenotype between microvascular ECs isolated from decidua (DECs) and ECs isolated from human skin (ADMECs).

Transcriptomics and Immunological Analyses Reveal a Pro-Angiogenic and Anti-Inflammatory Phenotype for Decidual Endothelial Cells.

C1q is the first subcomponent of the classical pathway of the complement system and belongs to the C1q/Tumor Necrosis Factor superfamily. C1q can perform a diverse range of immune and non-immune functions in a complement-dependent as well as -independent manner. Being a pattern recognition molecule of the innate immunity, C1q can recognize a number of self, non-self and altered-self ligands and bring about effector mechanisms designed to clear pathogens via opsonisation and inflammatory response. C1q is locally synthesized by macrophages and dendritic cells, and thus, can get involved in a range of biological processes, such as angiogenesis and tissue remodeling, immune modulation, and immunologic tolerance. The notion of C1q involvement in the pathogenesis of cancer is still evolving. C1q appears to have a dual role in cancer: tumor promoting as well as tumor-protective, depending on the context of the disease. In the current study, we performed a bioinformatics analysis to investigate whether C1q can serve as a potential prognostic marker for human carcinoma. We used the Oncomine database and the survival analysis platforms Kaplan-Meier plotter. Our results showed that high levels of C1q have a favorable prognostic index in basal-like breast cancer for disease-free survival, and in HER2-positive breast cancer for overall survival, while it showed a pro-tumorigenic role of C1q in lung adenocarcinoma, and in clear cell renal cell carcinoma. This  study, if validated via a retrospective study, can be a step forward in establishing C1q as a new tool as a prognostic biomarker for various carcinoma.

Is the Complement Protein C1q a Pro- or Anti-tumorigenic Factor? Bioinformatics Analysis Involving Human Carcinomas.

Microenvironment-related immune and inflammatory markers, when combined with established Ki-67 and morphology parameters, can improve prognostic prediction in gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NENs). Therefore, we evaluate the prognostic value of microenvironment and tumor inflammatory features (MoTIFs) in GEP-NENs. For this purpose, formalin-fixed paraffin-embedded tissue sections from 350 patients were profiled by immunohistochemistry for immune, inflammatory, angiogenesis, proliferation, NEN- and fibroblast-related markers. 314 patients were used to generate overall survival (OS) and disease-free survival (DFS) MoTIFs prognostic indices (PIs). PIs and additional variables were assessed using Cox models to generate nomograms for predicting 5-year OS and DFS. 36 patients were used for external validation of PIs and nomograms' prognostic segregations. From our analysis, G1/G2 vs G3 GEP-NENs showed phenotypic divergence with immune-inflammatory markers. HLA, CD3, CD8, and PD-1/PD-L1 IHC expression separated G3 into two sub-categories with high vs low adaptive immunity-related features. MoTIFs PI for OS based on COX-2 >4, PD-1 >0, CD8 <1, and HLA-I <1 was associated with worst survival [hazard ratio (HR) 2.50; 95% confidence interval (CI), 2.12-2.96; p<0.0001]. MoTIFs PI for DFS was based on COX-2 >4, PD-1 >4, HLA-I <1, HLA-I <2, HLA-DR <6 (HR 1.77; 95% CI, 1.58-1.99; p <0.0001). Two nomograms were developed including morphology (HR 4.83; 95% CI, 2.30-10.15; p <0.001) and Ki-67 (HR 11.32; 95% CI, 5.28-24.24; p <0.001) for OS, and morphology (PI=0: HR 10.23; 95% CI, 5.67-18.47; PI=5: HR 2.87; 95% CI, 1.21-6.81; p <0.001) and MoTIFs PI for DFS in well-differentiated GEP-NENs (HR 6.21; 95% CI, 2.52-13.31; p <0.001). We conclude that G1/G2 to G3 transition is associated with immune-inflammatory profile changes; in fact, MoTIFs combined with morphology and Ki-67 improve 5-year DFS prediction in GEP-NENs. The immune context of a subset of G3 poorly differentiated tumors is consistent with activation of adaptive immunity, suggesting a potential for responsiveness to immunotherapy targeting immune checkpoints. This article is protected by copyright. All rights reserved.

Article	Year
Transcriptomics and Immunological Analyses Reveal a Pro-Angiogenic and Anti-Inflammatory Phenotype for Decidual Endothelial Cells. International journal of molecular sciences\| PubMed ID: 30935090	2019
Is the Complement Protein C1q a Pro- or Anti-tumorigenic Factor? Bioinformatics Analysis Involving Human Carcinomas. Frontiers in immunology\| PubMed ID: 31130944	2019
Microenvironment and Tumor Inflammatory Features improve prognostic prediction in gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NENs). The journal of pathology. Clinical research\| PubMed ID: 31136102	2019

Alessandro Mangogna

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