👤 Matthieu Bouaziz

Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype, characterized by a lack of targeted therapies and poor prognosis. The tumor microenvironment (TME) plays a pivotal role in TNBC progression, with immune mediators such as cytokines, chemokines, growth factors, and immune checkpoints driving inflammation, angiogenesis, and immune evasion. We conducted a comparative analysis of 81 immune-related proteins in serum samples from 137 participants: 49 healthy controls (HC), 63 non-TNBC (NTNBC) patients, and 25 TNBC patients. Protein expression was quantified using multiplex immunoassays (ProcartaPlex and MILLIPLEX MAP® panels). Statistical analyses included principal component analysis (PCA), hierarchical clustering, receive operating curves (ROC), and pathway enrichment to identify diagnostic biomarkers and molecular networks associated with TNBC aggressiveness. Ou results revealed distinct immune dysregulation in TNBC, characterized by significant overexpression of pro-inflammatory cytokines (IFN-γ, IL-12p70, IL-8), chemokines (MIP-1α, Fractalkine), growth factors (VEGF-A, SCF), and immune checkpoints (LAG-3, PD-L1). ROC curve analyses identified LAG-3, Fractalkine, and VEGF-A as the top biomarkers distinguishing healthy controls from TNBC, while IL-5, IL-27, and TNF-β effectively discriminated TNBC from NTNBC. Cytokine network analysis highlighted TSLP, IL-12p70, and IL-17 A as central hubs coordinating Th1/Th17 inflammatory responses, stromal remodeling, and immune evasion, with strong interactions between IL-17 A-ENA-78-SCF and IL-3-IL-21 axes driving TNBC aggressiveness. Stratified analyses further demonstrated stage, grade, and metastasis revealed that IL-12p70, MIP-1α, and IL-18 were elevated in late-stage TNBC; IL-17 A, IL-5, and TWEAK were significantly overexpressed in high-grade tumors; and IFN-γ, IL-8, CTLA-4 and TSLP peaked in metastatic TNBC. Our findings identify immune mediator panels as promising diagnostic and prognostic biomarkers for TNBC. Show less

Circulating fatty acids (FA) have an endogenous or exogenous origin and are metabolized under the effect of many enzymes. They play crucial roles in many mechanisms: cell signaling, modulation of gene expression, etc., which leads to the hypothesis that their perturbation could be the cause of disease development. FA in erythrocytes and plasma rather than dietary FA could be used as a biomarker for many diseases. Cardiovascular disease was associated with elevated trans FA and decreased DHA and EPA. Increased arachidonic acid and decreased Docosahexaenoic Acids (DHA) were associated with Alzheimer's disease. Low Arachidonic acid and DHA are associated with neonatal morbidities and mortality. Decreased saturated fatty acids (SFA), increased monounsaturated FA (MUFA) and polyunsaturated FA (PUFA) (C18:2 n-6 and C20:3 n-6) are associated with cancer. Additionally, genetic polymorphisms in genes coding for enzymes implicated in FA metabolism are associated with disease development. FA desaturase (FADS1 and FADS2) polymorphisms are associated with Alzheimer's disease, Acute Coronary Syndrome, Autism spectrum disorder and obesity. Polymorphisms in FA elongase (ELOVL2) are associated with Alzheimer's disease, Autism spectrum disorder and obesity. FA-binding protein polymorphism is associated with dyslipidemia, type 2 diabetes, metabolic syndrome, obesity, hypertension, non-alcoholic fatty liver disease, peripheral atherosclerosis combined with type 2 diabetes and polycystic ovary syndrome. Acetyl-coenzyme A carboxylase polymorphisms are associated with diabetes, obesity and diabetic nephropathy. FA profile and genetic variants of proteins implicated in FA metabolism could be considered as disease biomarkers and may help with the prevention and management of diseases. Show less

Autosomal recessive (AR) STAT1 deficiency is a severe inborn error of immunity disrupting cellular responses to type I, II, and III IFNs, and IL-27, and conferring a predisposition to both viral and mycobacterial infections. We report the genetic, immunological, and clinical features of an international cohort of 32 patients from 20 kindreds: 24 patients with complete deficiency, and 8 patients with partial deficiency. Twenty-four patients suffered from mycobacterial disease (bacillus Calmette-Guérin = 13, environmental mycobacteria = 10, or both in 1 patient). Fifty-four severe viral episodes occurred in sixteen patients, mainly caused by Show less

Hereditary breast cancer accounts for 5-10% of all breast cancer cases. So far, known genetic risk factors account for only 50% of the breast cancer genetic component and almost a quarter of hereditary cases are carriers of pathogenic mutations in BRCA1/2 genes. Hence, the genetic basis for a significant fraction of familial cases remains unsolved. This missing heritability may be explained in part by Copy Number Variations (CNVs). We herein aimed to evaluate the contribution of CNVs to hereditary breast cancer in Tunisia. Whole exome sequencing was performed for 9 BRCA negative cases with a strong family history of breast cancer and 10 matched controls. CNVs were called using the ExomeDepth R-package and investigated by pathway analysis and web-based bioinformatic tools. Overall, 483 CNVs have been identified in breast cancer patients. Rare CNVs affecting cancer genes were detected, of special interest were those disrupting APC2, POU5F1, DOCK8, KANSL1, TMTC3 and the mismatch repair gene PMS2. In addition, common CNVs known to be associated with breast cancer risk have also been identified including CNVs on APOBECA/B, UGT2B17 and GSTT1 genes. Whereas those disrupting SULT1A1 and UGT2B15 seem to correlate with good clinical response to tamoxifen. Our study revealed new insights regarding CNVs and breast cancer risk in the Tunisian population. These findings suggest that rare and common CNVs may contribute to disease susceptibility. Those affecting mismatch repair genes are of interest and require additional attention since it may help to select candidates for immunotherapy leading to better outcomes. Show less