Prognostic significance of NLRP-3 expression in solid cancers: a systematic review and meta-analysis

Background The inflammasome is a critical immunological sensor comprised of NLRP-3, ASC, and CASPASE-1. Mutations in NLRP-3 are prevalent in inflammatory diseases. However, the role of NLRP-3 in cancer is controversial. This study investigates whether NLRP-3 expression is associated with clinical outcomes in patients with solid cancers.Methods PubMed (MEDLINE), Embase, Cochrane, and Google Scholar were searched for articles reporting NLRP-3 expression and disease outcome data in cancer patients. RevMan Review Manager was used to calculate pooled hazard ratios and Mantel–Haenszel pooled odds ratios. RNA sequencing datasets from the TCGA Pan-Cancer (PANCAN) were used for external validation.Results Patients with higher NLRP-3 expression showed a significant association with larger tumor size, advanced tumor grade, TNM stage, and presence of metastasis. High NLRP-3 expression has a significant association with poor OS (HR:2.12, 95% CI = 1.49–3.03), p < 0.0001) and DFS (HR:1.86, 95% CI = 1.30– 2.65, p = 0.0007). Subgroup analysis showed that higher NLRP-3 expression is associated with worse OS in head and neck cancer (HR: 2.77, 95% CI = 1.88–4.09, p < 0.00001), colorectal cancers (HR:2.14, 95% CI= 1.59– 2.87, p < 0.00001), and pancreatic cancer patients (HR: 3.19, 95% CI = 1.73–5.91, p = 0.0002).Conclusion High NLRP-3 expression is associated with advanced disease and poor outcomes in many solid tumours.