Identification of a NEK7-related pyroptosis gene signature against pancreatic cancer and evaluation of its potential in tumor microenvironment remodeling via regulating inflammasome complex

Abstract

The treatment options for pancreatic ductal adenocarcinoma (PDAC) remain limited. It is therefore important to explore new therapeutic targets and strategies for better treatment and prognosis for patients with PDAC. NIMA-related kinase 7 (NEK7) is a serine/threonine kinase involved in PDAC development. Moreover, NEK7 was reported to regulate NLRP3 inflammasome and cell pyroptosis. To evaluate the role of NEK7 in PDAC, we performed RNA sequencing analysis in PDAC cells, and a series of bioinformatics analyses were employed to determine the biological function of NEK7 in PDAC. We identified a NEK7-Specific Pyroptosis Gene Set (NEK7-SPGS) by high-throughput transcriptome sequencing combining Gene Set Enrichment Analysis (GSEA). We reveal that NEK7-SPGS is highly associated with T helper cell infiltration and inflammatory response of PDAC. We therefore proposed that NEK7-SPGS might have potential for tumor microenvironment remodeling via T cells induced inflammatory response. Using dataset from TCGA database, we established a NEK7-SPGS-related prognostic signature for patients with PDAC. Subsequently, sensitivity estimation of chemotherapeutic drugs revealed a series of chemotherapy agents according to the NEK7-SPGS-related prognostic signature, including gemcitabine and paclitaxel, drugs that have been used as conventional agents for PDAC therapy. Meanwhile, we showed that the expression of SCAMP1, which is a member of NEK7-SPGS, was involved in the progression of PDAC in vivo and in vitro. We proposed a NEK7-specific pyroptosis gene signature and evaluated its potential in PDAC tumor microenvironment. The NEK7-SPGS-related prognostic signature could act as a prognostic biomarker and serve as therapeutic guidance in clinical application.