Prognostic value of inflammation-based prognostic scores in patients with colorectal cancer

Background: Anatomopathological staging is the primary method to determine the prognosis of patients with colorectal carcinoma (CRC). However, new tools have been developed that can complement it, such as the analysis of the elevation of systemic inflammatory markers. Objective: To evaluate the impact of the elevation of scores based on inflammatory markers (the neutrophil-to-lymphocyte ratio [NLR], the Glasgow Prognostic Score [GPS], and isolated C-reactive protein [CRP]) in the prognosis of patients diagnosed with CRC and submitted to potentially curative surgery in Hospital de Braga, Portugal, between January 1st, 2005, and December 31st, 2010. Methods: A retrospective analysis of the data of 426 patients was performed, with a collection of several clinico-pathological variables, as well as the levels of lymphocytes, neutrophils, albumin and CRP, in the pre- and postoperative periods, to apply the different scores to the sample. Results: From the analysis of the survival curves, we concluded that patients with increased NLR in the pre- and postoperative periods present a lower cancer-related survival than patients with normal NLR (preoperative period: 93.7 versus 122 months; p<0.001; postoperative period: 112 versus 131 months; p=0.002). Patients with increased NLR in the pre- and postoperative periods also had a lower disease-free survival (preoperative period: 88.0 versus 122 months; p<0.001; postoperative period: 111 versus 132 months; p=0.002). In addition, increased pre- and postoperative NLR was associatedwith a higher risk of death due to CRC (preoperatively: hazard ratio [HR]=2.25; p<0.001; postoperatively: HR=2.18; p=0.003). However, the multivariate analysis shows that only postoperative NLR (ajusted HR =2.66; p=0.002) does so independently of the remaining variables. Conclusion: Regarding the scores applied to the sample, the NLR was the one that most consistently related to the prognosis of the patients. However, it would be useful to develop a prospective study that could confirm this relationship. (AU)

Estrogen receptors participate in carcinogenesis signaling pathways by directly regulating NOD-like receptors.

Increasing evidence indicates that the NOD-like receptors (NLRs) family may act as critical back-up defenses and provide synergistic responses when confronted with persistent danger. However, the precise regulatory mechanism of NLRs and the contribution of NLRs to cancer are still unknown. In our previous study, we found that estrogen receptors (ERs) have a close connection with NLRs in the inflammatory response. Here, ERs are first identified as NLRs transcription regulation factors, both regulate NLRs expression and promote inflammasome co-localization. Furthermore, we identified that NLRP3 was differentially expressed in colon normal and cancer cells, selective ERα antagonist could significantly decrease pro-inflammatory cytokines expression, suppress proliferation and promote apoptosis by inhibited NLRP3 expression and inflammasome activity. In short, the research demonstrates that ERs participate in the NLR-associated signaling pathway in cancer by directly regulating NLRs. Our results provide novel insight into ERs as therapeutic targets in NLR-related inflammation and cancer.