Low-level NLRP1 is associated with increased metastasis and risk of recurrence of non-melanoma skin cancer.

BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) and cutaneous basal cell carcinoma (cBCC) are the most common types of non-melanoma skin cancer (NMSC). The NACHT, LRR and PYD domains-containing protein 1 (NLRP1) protein is considered to be inhibited in NMSC, although clinical evidence is still lacking. OBJECTIVES: To investigate the clinical significance of NLRP1 in cSCC and cBCC patients. MATERIAL AND METHODS: This prospective observational study enrolled 199 cases of cBCC and cSCC patients who reported to our hospital from January 2018 to January 2019. Additionally, 199 blood samples from healthy individuals were collected as the control. Serum NLRP1 and cancer biomarkers of CEA and CYFRA21-1 were then measured using enzyme-linked immunosorbent assay (ELISA). Clinical characteristics collected from patients included age, sex, BMI, TNM stage, cancer type, lymph node metastasis, and myometrial infiltration conditions. All patients were followed up for 1-3 years. RESULTS: Of all patients, 23 died during the follow-up period, with a mortality rate of 11.56%. Serum NLRP1 showed markedly lower levels in cancer patients compared with healthy controls. Furthermore, the expression of NLRP1 was significantly higher in cBCC patients compared with cSCC patients. The deceased patients, together with those with lymph node metastasis and myometrial infiltration, also showed significantly lower NLRP1 levels. Moreover, lower NLRP1 levels were associated with higher frequencies of tumor-nodule-metastasis (TNM) III-IV stage, lymph node metastasis and myometrial infiltration, as well as higher mortality and recurrence rates. The curvilinear regression showed the relationship between NLRP1 and CEA/or CYFRA21-1 was most appropriate for the reciprocal. Receiver operating characteristic (ROC) curves showed NLRP1 was a potential biomarker for lymph node metastasis, myometrial infiltration and prognosis in NMSC patients, and the Kaplan-Meier analysis found NLRP1 was associated with 1-3-year mortality and recurrence of NMSC. CONCLUSIONS: Lower NLRP1 level is associated with worse clinical outcomes and poorer prognosis in cSCC and cBCC patients.