Downstream Signaling of Inflammasome Pathway Affects Patients’ Outcome in the Context of Distinct Molecular Breast Cancer Subtypes

Abstract

Inflammasomes are protein complexes involved in the regulation of different biological conditions. Over the past few years, the role of NLRP3 in different tumor types has gained interest. In breast cancer (BC), NLRP3 has been associated with multiple processes including epithelia mesenchymal transition, invasion and metastization. Little is known about molecular modifications of NLRP3 up-regulation. In this study, in a cohort of BCs, the expression levels of NLRP3 and PYCARD were analyzed in combination with CyclinD1 and MYC ones and their gene alterations. We described a correlation between the NLRP3/PYCARD axis and CyclinD1 (p < 0.0001). NLRP3, PYCARD and CyclinD1's positive expression was observed in estrogen receptor (ER) and progesterone receptor (PgR) positive cases (p < 0.0001). Furthermore, a reduction of NLRP3 and PYCARD expression has been observed in triple negative breast cancers (TNBCs) with respect to the Luminal phenotypes (p = 0.017 and p = 0.0015, respectively). The association NLRP3+/CCND1+ or PYCARD+/CCND1+ was related to more aggressive clinicopathological characteristics and a worse clinical outcome, both for progression free survival (PFS) and overall survival (OS) with respect to NLRP3+/CCND1− or PYCARD+/CCND1− patients, both in the whole cohort and also in the subset of Luminal tumors. In conclusion, our study shows that the NLRP3 inflammasome complex is down-regulated in TNBC compared to the Luminal subgroup. Moreover, the expression levels of NLRP3 and PYCARD together with the alterations of CCND1 results in Luminal subtype BC's poor prognosis.

The Co-Localization of NLRP3 and ASC Specks Does Not Automatically Entail NLRP3 Inflammasome Functionality in PDAC Cell Lines

“…We also observed a difference in the ASC amount between cell lines, but a higher ASC amount was not associated with more ASC speck formation. A high expression of ASC protein is often used as a marker for inflammasome formation in multiple types of cancer [21,31,[43][44][45][46][47][48][49]. The ASC protein levels [13] and PYCARD gene expression [50] (Figure 5e) were increased in the PDAC tissue, but our results imply that the ASC amount alone may be a poor marker for inflammasome formation.…”

VEGFA Status as a Predictive Marker of Therapy Outcome in Metastatic Gastric Cancer Patients Following Ramucirumab-Based Treatment

“…For each case, at least 20 non-overlapping nuclei were analyzed. The VEGFA copy number was evaluated as reported in https://doi.org/10.3390/ph15060651 accessed on 1 June 2023 [25].…”

Agri-Food By-Products in Cancer: New Targets and Strategies

“…Most BC patients exhibit increased levels of inflammasome components, such as interleukins (IL-1β and IL-18) compared with their normal counterparts. Again, elevated serum levels of IL-1βb in BC patients is associated with the establishment of inflammatory TME, tumor progression, and acquisition of a metastatic phenotype [ 98 ].…”