甲状腺乳头状癌术前中医证型与临床病理特征及NLRP3表达的关系

Correlation between preoperative traditional Chinese medicine syndromes，clinicopathological features，and NLRP3 expression in papillary thyroid carcinoma

关键词:  中医证型  甲状腺乳头状癌  NLRP3炎症小体  临床病理特征

Key words:  traditional Chinese medicine syndromes  papillary thyroid carcinoma  NOD-like receptor pyrin domain-containing 3 inflammasome  clinicopathological characteristics

摘要:

[目的] 分析甲状腺乳头状癌（PTC）患者术前中医证型的分布及不同证型间临床病理特征的差异，探究中医证型与PTC组织中核苷酸结合寡聚结构域样受体蛋白3（NLRP3）表达的相关性。[方法] 选取2022年7月—2023年3月于南京中医药大学附属医院普外科行手术治疗的190例PTC患者，术前辨证分型为肝郁气滞、痰瘀互结证、瘀热内结证3种证型。收集患者年龄、性别、术后病理分期、癌灶最大直径、淋巴结转移情况、癌灶数量、癌组织侵袭周围组织情况，并用免疫组化法检测190例患者PTC组织中NLRP3表达情况。统计分析PTC患者术前中医证型的分布特点及其分型与术后临床病理特征及NLRP3表达的相关性。[结果] 190例PTC患者中痰瘀互结证81例（42.6%）>肝郁气滞证61例（32.1%）>瘀热内结证48例（25.3%）。各证型在性别、年龄、癌灶数量及周围组织侵犯情况比较，差异无统计学意义（P＞0.05）。Ⅰ期中肝郁气滞证患者比例、Ⅱ~Ⅳ期中瘀热内结证患者比例均高于痰瘀互结证（P＜0.05）；瘀热内结证患者中淋巴结转移的比例高于其他证型（P＜0.05）；与痰瘀互结证相比，肝郁气滞证患者癌灶最大直径多＜0.8 cm，瘀热内结证患者癌灶最大直径多≥0.8 cm（P＜0.05）。190例患者中NLRP3阳性表达率为64.2%，瘀热内结证患者PTC组织NLRP3蛋白免疫组化评分高于其他两种证型（P＜0.05）；肝郁气滞证及痰瘀互结证在有无周围组织侵犯及癌灶最大直径是否超过0.8 cm的患者间NLRP3表达差异有统计学意义（P＜0.05）；瘀热内结证在有无淋巴结转移及有无周围组织侵犯的患者间NLRP3表达差异有统计学意义（P＜0.05）。[结论] PTC患者术前以痰瘀互结证及肝郁气滞证为主，NLRP3阳性表达有助于区分瘀热内结证与痰瘀互结证及肝郁气滞证，并与各证型术后病理特征具有一定的关联。

Abstract:

[Objective] To analyze the clinicopathological characteristics of patients with papillary thyroid carcinoma（PTC） before surgery and the distribution of traditional Chinese medicine syndromes. Furthermore，to examine the relationship between traditional Chinese medicine syndromes and expression of NOD-like receptor pyrin domain-containing 3（NLRP3） in PTC tissues. [Methods] A total of 190 patients with PTC who received surgical treatment in Affiliated Hospital of Nanjing University of Chinese Medicine from July 2022 to March 2023 were selected as the research subjects，and the preoperative diagnostic was divided into three types：stagnation of liver-qi，phlegm-stasis cementation，heat and blood stasis syndrome. The clinicopathological features of the patients（sex，age，tumor size，pathological type，condition of metastatic lymph nodes and invasion of surrounding tissues，and tumor number） were collected. Protein expression in PTC tissues was determined by immunohistochemistry. The distribution characteristics of traditional Chinese medicine syndromes and the correlation between syndrome types and NLRP3 expression were statistically analyzed. [Results] In the study，including 190 cases of PTC，81 cases（42.6%） had phlegm-stasis intertwining syndrome，61 cases（32.1%） had stagnation of liver-qi，and 48 cases（25.3%） had heat and blood stasis. The differences of age，gender，tumor number and invasion of surrounding tissues between all syndromes were not statistically significant（P>0.05）. The proportion of patients with stagnation of liver-qi syndrome in pathological type Ⅰ and the proportion of patients with heat and blood stasis syndrome in pathological type Ⅱ to Ⅳ were higher than those with phlegm-stasis intertwining syndrome syndrome（P<0.05）. The rate of metastatic lymph nodes was higher in patients with heat and blood stasis than other patients（P<0.05）. Compared with phlegm-stasis intertwining syndrome syndrome，the largest tumor size in patients with stagnation of liver-qi were more often <0.8 cm，and patients with heat and blood were more often≥0.8 cm（P<0.05）. The positive expression rate of NLRP3 in PTC patients was 64.2%，with higher positive rates and immunohistochemical score in PTC tissues of patients with heat and blood stasis（P<0.05）. The expression of NLRP3 showed statistically significant differences（P<0.05） in both liver-qi stagnation syndrome and phlegm-stasis intermingling syndrome，depending on the presence of surrounding tissue invasion and whether the maximum tumor diameter exceeded 0.8 cm. In heat and blood stasis syndrome，significant differences in NLRP3 expression were observed between patients with and without lymph node metastasis and surrounding tissue invasion（P<0.05）. [Conclusion] The stagnation of liver-qi and phlegm-stasis intertwining syndrome were the most TCM syndrome in PTC patients. The positive expression of NLRP3 contribute to discriminate the heat and blood stasis syndrome from the phlegm-stasis cementation and stagnation of liver-qi syndromes，and NLRP3 expression was associated with certain post-operative clinicopathological characteristics in three syndromes.