Abstract: Objective To explore the correlation between serum V-set and immunoglobulin domain containing 4 (VSIG4),the protein encoded by the multiple endocrine neoplasia type 1 gene (menin) with immune infiltration in patients with papillary thyroid carcinoma (PTC),and their impact on prognosis.Methods From February 2019 to February 2022,168 PTC patients treated with thyroidectomy (PTC group),168 patients with benign thyroid lesions (benign nodules group),and 168 healthy individuals with normal thyroid function (healthy group) in our hospital were considered as the study subjects.According to whether there was recurrence or death within 3 years after thyroidectomy,the 168 PTC patients were included into 138 cases in the good prognosis group and 30 cases in the poor prognosis group.ELISA method was used to detect serum VSIG4 and menin.Bioinformatics (TISDIB database) was used to explore the correlation between VSIG4,menin,and five types of tumor infiltrating immune cells in PTC patients.Kaplan-Meier survival curves were plotted to explore the relationship between high/low VSIG4,menin levels and disease-free survival.Multifactorial COx method was used to explore the factors influencing the recurrence/death.ROC curve was plotted to evaluate the predictive value of VSIG4 and menin for recurrence/death.Results Serum VSIG4 levels in PTC group,benign nodule group,healthy group were （6.59±1.42）ng/ml,（5.14±1.20）ng/ml,（3.29±0.86）ng/ml respectively,and it was higher in PTC group than the benign nodule group and the healthy group (P<0.05).Serum menin levels in PTC group,benign nodule group,healthy group were （5.02±1.34）ng/ml,（6.47±1.67）ng/ml,（8.15±1.88）ng/ml respectively,and it was lower in PTC group than the benign nodule group and the healthy group (P<0.05).The analysis results of TISDIB database showed that the VSIG4 and menin were correlated with five types of tumor infiltrating immune cells in PTC patients,and the correlation of VSIG4 with immune infiltration in PTC patients was higher than the correlation of menin (P<0.05).The poor prognosis group had prominently higher proportion of lymph node dissection,VSIG4,and proportion of TNM stage Ⅲ,and prominently lower menin than the good prognosis group (P<0.05).The disease-free survival rate of PTC patients with VSIG4 ≥ 6.50ng/ml was greatly lower than that of patients with VSIG4<6.50ng/ml,and the disease-free survival rate of PTC patients with menin ≤ 5.11ng/ml was greatly higher than that of patients with menin>5.11ng/ml (χ2=9.217,16.407,P<0.05).TNM stage Ⅲ and VSIG4 were risk factors for recurrence/death in PTC patients,while menin and lymph node dissection were protective factors (P<0.05).The combined prediction of VSIG4 and menin had an AUC of 0.919 (95%CI 0.868-0.970) for predicting recurrence/death in PTC patients,which was superior to the single prediction of VSIG4 (Z=2.206,P<0.05) and menin (Z=2.376,P<0.05).Conclusion Serum VSIG4 is elevated and menin is reduced in patients with PTC .Both are correlated with five types of tumor infiltrating immune cells in PTC patients.The combined prediction of VSIG4 and menin has a high value in predicting the prognostic recurrence/death in PTC patients.

Key words: V-set and immunoglobulin domain containing 4, protein encoded by the multiple endocrine neoplasia type 1 gene, papillary thyroid carcinoma, immune infiltration, correlation, prognosis