In recent years, the use of traditional clinicopathological indicators for the early HNSCC diagnosis and prediction of the prognosis has been insufficient [12, 13]. Therefore, new prognostic biomarkers that fully reflect the biological characteristics of tumors and the treatment efficacy of patients with HNSCC have been under investigation. To date, many studies have been conducted to identify predictive biomarkers in HNSCC patients. These potential biomarkers are divided into single-molecule protein markers and gene markers that can be identified through high-throughput analysis and gene expression profiling [14–16].
NLRP are involved in the progression of a variety of cancers ; however, their functions in HNSCC remain unknown. Our results showed that the mRNAs and proteins of 12 NLRP family members were overexpressed in HNSCC. The overexpression was significantly associated with the cancer stage in HNSCC and was also remarkably associated with shorter OS. Additionally, the mutation and genetic alteration rates of NLRPs were higher in HNSCC patients. Analysis of the functions and pathways of NLRPs and their altered neighbor genes suggested the involvement of NLRPs in the following biological processes: defense response to other organisms, I-kappaB kinase/NF-kappaB signaling, regulation of the production of type I interferons, interleukin-1, interleukin-18, pyroptosis, NLRP3 inflammasome complex assembly, female gamete generation, response to interferon-gamma, positive regulation of organelle organization, protein processing, and positive regulation of cellular component biogenesis. KEGG analysis confirmed the functions of the NLRP1 inflammasome in the regulation of the innate immune responses to cytosolic DNA and interleukin-1 processing.
Previous studies have suggested that NLRPs play a role in various cancers. Polymorphism or mutation of NLRP1A is closely related to the progression of cancer . NLRP3 plays a vital role in the metastasis and prognosis of NPC and other cancers [19–21]. NLRP4 (a cytosolic receptor in several tissues ) has recently been confirmed to not only inhibit autophagy [23, 24] but also to function in the immune response to viral infections (eg Epstein-Barr virus, human papilloma virus) , thereby indirectly contributing to the development of NPC. NLRP7 had been reported in previous studies as the main pathogenic gene for recurrent hydatidiform moles (RHMs) . NLRP12 deficiency leads to colitis and inflammation-induced tumorigenesis in mice [27, 28].
The NLRP family is significantly related to the progression of NPC in studies. Therefore, we further explored the miRNAs downstream of NLRPs involved in NPC. The results indicated that miR-199a-3p regulates the expression of NLRP1, miR-125a-5p regulates the expression of NLRP2, and miR-22 regulates the expression of NLRP3. It has previously been demonstrated in some cancers that miR-22 targets NLRP3 during carcinogenesis . miR-125a-5p reportedly targets ERBB3 and inhibits cell proliferation, cell cycle progression, and cell migration in head and neck cancers . In another study, up-regulated miR-125a-5p was found to enhance the metastatic ability of HNSCC cell lines [31, 32]. In addition, miR-125a-5p has been identified as an important cancer treatment target in a series of cancers, including gastric cancer , cervical cancer , and lung cancer . miR-199a-3p is not only expressed abnormally in a variety of cancers but also regulates ITGA3 to inhibit metastasis in head and neck cancer . In a recently published study, bioinformatics analysis established miR-199a-3p as an important target for the treatment of head and neck cancer .
Our research has certain limitations. First, due to the small sample size in the online databases used, the breadth of our research findings is limited. A larger sample size is needed for further research to confirm our findings and explore the role of NLRPs in HNSCC. Second, our study lacks information on the diagnostic value of NLRPs in HNSCC; therefore, further research is needed to investigate whether NLRPs can be used as diagnostic biomarkers. Finally, because we did not uncover the underlying mechanisms for NLRP in HNSCC, our research lacks depth.
In brief, our research results confirm that the over-expression of 12 NLRPs is associated with the cancer stage in HNSCC patients. Multivariate analysis showed that higher expression of NLRPs was significantly associated with shorter OS in HNSCC patients. This study demonstrates that the NLRP family can be prognostic biomarkers for HNSCC patients. We also explored the miRNA targets downstream of NLRPs in patients with NPC, laying the foundation for further research.