Expression of nicotinamide -N- methyltransferase in various tumor tissues and its prognostic value in papillary thyroid carcinoma / 肿瘤研究与临床

ABSTRACT

Objective:To investigate the expression of nicotinamide-N-methyltransferase (NNMT) in various tumor tissues and its prognostic value in papillary thyroid carcinoma.Methods:The paraffin samples of surgically resected tissues from 168 cases of colorectal cancer, 75 cases of gastric cancer, 178 cases of lung cancer, 15 cases of liver cancer, 60 cases of thyroid cancer, 7 cases of prostate cancer, 74 cases of breast cancer, and 14 cases of renal cancer were collected from Sir Run Run Show Hospital, Zhejiang University School of Medicine and the Third Affiliated Hospital of Zhejiang University of Traditional Chinese Medicine between January 2016 and December 2021; tissue samples of 58 cases of papillary thyroid cancer and another 19 cases of thyroiditis were collected between January 2016 and December 2016. Immunohistochemistry kits were prepared and performance tests were performed. Normal specimens (>5 cm from the margin of paracancerous tissues) and the samples of gastric cancer, colorectal cancer, lung cancer, thyroid cancer, prostate cancer, breast cancer, and kidney cancer tissues as well as their paracancerous tissues (3 cm from the tumor edge) were selected. Immunohistochemistry kits were used to detect the expression of NNMT protein in normal tissue samples, different tumor tissues and their paracancerous tissues. X-tile software combined with the receiver operating characteristics curve of NNMT in the diagnosis of tumor tissues and paracancerous tissues in papillary throid carcinoma were used to determine the optimal cut-off value (41.5); < 41.5 was treated as the NNMT protein low expression group and ≥ 41.5 was treated as the NNMT protein high expression group. The expression of NNMT protein in patients with papillary thyroid carcinoma with different clinicopathological characteristics was compared; Kaplan-Meier method was used to analyze the overall survival of the patients with papillary thyroid carcinoma; Cox proportional risk model was used to conduct multivariate analysis on the influencing factors of overall survival.Results:The prepared immunohistochemistry kits were valid for at least 12 months, with good intra-batch and batch-to-batch repeatability, good stability and specificity. NNMT protein was not or occasionally lowly expressed in colorectal, lung, thyroid, prostate, breast, kidney, and gastric tissues. NNMT protein was highly expressed in colorectal cancer, gastric cancer, breast cancer, kidney cancer, thyroid cancer, lung cancer, prostate cancer tissues, while lowly expressed in colorectal cancer, gastric cancer, breast cancer, kidney cancer, thyroid cancer, lung cancer, prostate cancer adjacent tissues. The high expression rates of NNMT protein in thyroiditis tissue, papillary thyroid cancer tumor tissue and paracancerous tissues were 15.79% (3/19), 68.97% (40/58) and 31.03% (18/58), respectively, and the high expression rate of NNMT protein in papillary thyroid carcinoma tissue was higher than that in thyroiditis tissue and paracancerous tissue. All patients with papillary thyroid cancer were divided into the NNMT protein high expression group (40 cases) and the low expression group (18 cases). There were no statistically significant differences in NNMT protein expression among patients with different age, gender, degree of differentiation, lump diameter, TNM stage, lymph node metastasis, and serum anti-thyroglobulin antibody (TgAb) level (all P > 0.05). The median overall survival time of 58 patients was 18.5 months, and the 5-year overall survival rate was 90.0%. The overall survival of patients with a lump diameter of ≥2 cm was worse than that of those with a lump diameter of < 2 cm ( P < 0.001), and the overall survival of patients with lymph node metastasis was worse than that of those without lymph node metastasis ( P = 0.041). The overall survival of patients in the NNMT protein high expression group was worse than that of those in the NNMT protein low expression group, and the overall survival of patients with high serum TgAb level was worse than that of those with low serum TgAb level, while the differences were not statistically significant (all P >0.05). Lump diameter ( HR = 35.56, 95% CI 2.64-478.25, P = 0.007), NNMT protein expression ( HR = 308.12, 95% CI 2.21-42 958.20, P = 0.023), serum TgAb level ( HR = 142.85, 95% CI 1.88-10 854.25, P = 0.025) were independent influencing factors for the OS of patients with papillary thyroid carcinoma. Conclusions:NNMT is highly expressed in various tumor tissues. NNMT expression is related to the prognosis of patients with papillary thyroid carcinoma;the patients with high expression of NNMT have worse prognosis compared with those with low expression of NNMT.