Annexin A3 in sepsis: novel perspectives from an exploration of public transcriptome data
IMMUNOLOGY
Authors: Toufiq, Mohammed; Roelands, Jessica; Alfaki, Mohamed; Syed Ahamed Kabeer, Basirudeen; Saadaoui, Marwa; Lakshmanan, Arun Prasath; Bangarusamy, Dhinoth Kumar; Murugesan, Selvasankar; Bedognetti, Davide; Hendrickx, Wouter; Al Khodor, Souhaila; Terranegra, Annalisa; Rinchai, Darawan; Chaussabel, Damien; Garand, Mathieu
Abstract
According to publicly available transcriptome datasets, the abundance of Annexin A3 (ANXA3) is robustly increased during the course of sepsis; however, no studies have examined the biological significance or clinical relevance of ANXA3 in this pathology. Here we explored this interpretation gap and identified possible directions for future research. Based on reference transcriptome datasets, we found that ANXA3 expression is restricted to neutrophils, is upregulatedin vitroafter exposure to plasma obtained from septic patients, and is associated with adverse clinical outcomes. Secondly, an increase in ANXA3 transcript abundance was also observedin vivo, in the blood of septic patients in multiple independent studies. ANXA3 is known to mediate calcium-dependent granules-phagosome fusion in support of microbicidal activity in neutrophils. More recent work has also shown that ANXA3 enhances proliferation and survival of tumour cells via a Caspase-3-dependent mechanism. And this same molecule is also known to play a critical role in regulation of apoptotic events in neutrophils. Thus, we posit that during sepsis ANXA3 might either play a beneficial role, by facilitating microbial clearance and resolution of the infection; or a detrimental role, by prolonging neutrophil survival, which is known to contribute to sepsis-mediated organ damage.
Quantitative tissue proteomic investigation of invasive ductal carcinoma of breast with luminal B HER2 positive and HER2 enriched subtypes towards potential diagnostic and therapeutic biomarkers
JOURNAL OF PROTEOMICS
Authors: Pendharkar, Namita; Gajbhiye, Akshada; Taunk, Khushman; RoyChoudhury, Sourav; Dhali, Snigdha; Seal, Shubhendu; Mane, Anupama; Abhang, Subodhini; Santra, Manas K.; Chaudhury, Koel; Rapole, Srikanth
Abstract
Worldwide, breast cancer is one of the frequently diagnosed cancers in women with high mortality if not diagnosed at early stage. Although biomarker discoveries through various proteomic approaches have been studied in breast cancer, a limited number of studies have explored the invasive ductal carcinoma with Luminal B HER2 positive (LB) and HER2 enriched (HE) subtypes. The present study employed the complementary quantitative proteomic approaches to find a panel of markers that could discriminate LB and HE subtypes as well as early (ES) and late stages (LS) of these subtypes. A total of 67 and 68 differentially expressed proteins were identified by DIGE for the subtype and stage wise categories, respectively. Multivariate statistical analysis was employed to identify the set of most significant proteins, which could discriminate between these two subtypes and also early and late stages under study. Immunoblotting and MRM based validation in a separate cohort of samples confirmed that panel of biosignatures for LB are APOA1, GELS, HS90B, EF1A1, NHRF1 and PRDX3 and for HE are PRDX1, CATD, CALR, ATPB and CH60. For the diagnosis of early and late stages the potential markers are TPM4, CATD, PRDX3, ANXA3, HSPB1 and CALR, TRFE, GELS, CH60, CAPG, NHRF1, 1433G, GRP78 respectively. (C) 2015 Elsevier B.V. All rights reserved.