Accuracy of calprotectin using the Quantum Blue Reader for the diagnosis of spontaneous bacterial peritonitis in liver cirrhosis.

AIM: We aimed to evaluate the accuracy of the dosage of calprotectin in ascitic fluid (AF) using the Quantum Blue assay, for the prompt diagnosis of spontaneous bacterial peritonitis (SBP). METHODS: We prospectively collected 236 AF samples from 119 cirrhotic patients hospitalized in two French centers between May 2016 and May 2017. Bloody and chylous/cloudy AF, and secondary peritonitis were excluded. SBP was diagnosed if neutrophils in AF were >250/mm3 using standard cytology. The Quantum Blue Reader selectively measured the calprotectin antigen (MRP8/14) in 12 min within the measurable range from 0.18 to 1.80 µg/mL; values outside this range were registered as 0.17 and 1.81 µg/mL. RESULTS: A total of 36 AF were considered as SBP (15.2%). SBP had higher median levels of calprotectin than non-SBP (1.81 vs. 0.25 µg/mL, P < 0.001). Calprotectin levels were positively correlated with neutrophils in AF (r = 0.57, P < 0.001) and C-reactive protein (r = 0.43, P < 0.001), but not with the Child-Pugh and Model for End-Stage Liver Disease scores. The optimal threshold of calprotectin to diagnose SBP was set at 1.51 µg/mL (80th percentile of calprotectin), yielding sensitivity, specificity, and positive and negative predictive values of 86.1%, 92.0%, 65.9%, and 97.3%, respectively. Only one asymptomatic patient with SBP had a low calprotectin level, but a high serum C-reactive protein level that strongly suggested an ongoing infection. We also showed that intraclass correlation coefficients for inter- and intra-observer agreement were excellent, with 0.95 and 0.89, respectively. CONCLUSIONS: The dosage of calprotectin in AF using the Quantum Blue assay is a rapid and reliable method of ruling out SBP in hospitalized cirrhotic patients.

Autophagy is associated with a robust specific transcriptional signature in breast cancer subtypes.

Previous works have described that autophagy could be associated to both pro- and anti-cancer properties according to numerous factors, such as the gene considered, the step of autophagy involved or the cancer model used. These data might be explained by the fact that some autophagy-related genes may be involved in other cellular processes and therefore differently regulated according to the type or the grade of the tumor. Indeed, using different approaches of transcriptome analysis in breast cancers, and further confirmation using digital PCR, we identified a specific signature of autophagy gene expression associated to Luminal A or Triple Negative Breast Cancers (TNBC). Moreover, we confirmed that ATG5, an autophagy gene specifically expressed in TNBC, favored cell migration, whereas BECN1, an autophagy gene specifically associated with ER-positive breast cancers, induced opposite effects. We also showed that overall inhibition of autophagy promoted cell migration suggesting that the role of individual ATG genes in cancer phenotypes was not strictly dependent of their function during autophagy. Finally, our work led to the identification of TXNIP1 as a potential biomarker associated to autophagy induction in breast cancers. This gene could become an essential tool to quantify autophagy levels in fixed biopsies, sort tumors according to their autophagy levels and determine the best therapeutic treatment.

Epigenetic Control of Autophagy in Cancer Cells: A Key Process for Cancer-Related Phenotypes.

Although autophagy is a well-known and extensively described cell pathway, numerous studies have been recently interested in studying the importance of its regulation at different molecular levels, including the translational and post-translational levels. Therefore, this review focuses on the links between autophagy and epigenetics in cancer and summarizes the. following: (i) how ATG genes are regulated by epigenetics, including DNA methylation and post-translational histone modifications; (ii) how epidrugs are able to modulate autophagy in cancer and to alter cancer-related phenotypes (proliferation, migration, invasion, tumorigenesis, etc.) and; (iii) how epigenetic enzymes can also regulate autophagy at the protein level. One noteable observation was that researchers most often reported conclusions about the regulation of the autophagy flux, following the use of epidrugs, based only on the analysis of LC3B-II form in treated cells. However, it is now widely accepted that an increase in LC3B-II form could be the consequence of an induction of the autophagy flux, as well as a block in the autophagosome-lysosome fusion. Therefore, in our review, all the published results describing a link between epidrugs and autophagy were systematically reanalyzed to determine whether autophagy flux was indeed increased, or inhibited, following the use of these potentially new interesting treatments targeting the autophagy process. Altogether, these recent data strongly support the idea that the determination of autophagy status could be crucial for future anticancer therapies. Indeed, the use of a combination of epidrugs and autophagy inhibitors could be beneficial for some cancer patients, whereas, in other cases, an increase of autophagy, which is frequently observed following the use of epidrugs, could lead to increased autophagy cell death.