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OBJECTIVE: To explore the influencing factors and cumulative risk of lymph node metastasis (LNM) in papillary thyroid microcarcinoma (PTMC) patients. METHODS: 607 patients confirmed PTMC pathologically after thyroidectomy were enrolled in this retrospective study. The rate of LNM was calculated. Different clinicopathological characteristics were compared in PTMC patients with and without LNM and in different subgroups of LNM, respectively. Correlation between clinicopathological characteristics and LNM was analyzed and the cumulative risk of LNM according to different clinicopathological characteristics was calculated. RESULTS: (1) There were 228 cases (37.56%) of PTMC combined with LNM. Compared with the non-lymph node metastasis group, the proportion of age <55 years, male, multiple foci, bilateral foci, diameter>0.5cm, extracapsular invasion, HT and intermediate-to-high risk stratification for recurrence of the LNM group was significantly increased (all p<0.05);(2) Multivariate logistic regression analysis showed that age <55years, male, multiple foci, diameter>0.5cm,HT were independently positively correlated with LNM (all p <0.05); (3) Subgroup analysis showed that women aged <55 years combined with HT and aged≥55 years combined with BMI≥25 kg/m2 were independently positively associated with LNM; (4) With the increase of the tumor diameter, the cumulative risk of LNM in group of age <55 years, males, and multiple foci increased gradually, and was higher than those of age≥55 years, females and single foci, respectively. (5) Among the 228 cases of LNM, the proportion of lymph nodes (LN) >5 and the positive rate of LN were both higher in male group than that in the female group. The proportion of multiple foci and HT in LLNM group was higher than that in CLNM group (all P<0.05). CONCLUSION: Age <55 years, males, multiple foci, diameter >0.5cm and HT were independent risk factors of LNM; HT was an independent risk factor for LNM in female <55 years old, and BMI≥25 kg/m2 was an independent risk factor for LNM in female ≥55 years old; The increase of tumor diameter in age <55 years, males, multiple foci, and bilateral foci increased the cumulative risk of LNM, respectively; The number of LNM and the positive rate of LNM were both higher in male, and patients with multiple foci or HT were more likely to develop into LLNM.
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INTRODUCTION: Thyroid cancer is a familiar kind of cancer. Natural products are promising therapeutic approaches in treating thyroid cancer. Triptolide is a diterpenoid epoxide extracted from Tripterygium wilfordii. The mechanism of triptolide in the treatment of thyroid cancer has not been investigated clearly. METHODS: We evaluated triptolide targets and thyroid cancer targets with related databases. The protein-protein interaction (PPI) networks of the triptolide targets and thyroid cancer targets were constructed with Cytoscape software. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of the core PPI network were obtained. Molecular docking analysis was used to evaluated the binding of triptolide with core targets. Furthermore, apoptosis assays, real-time polymerase chain reaction (RT-PCR) and Western blotting were used to evaluate the anticancer functions of triptolide. RESULTS: Triptolide had 34 targets, and thyroid cancer had 210 targets. The core PPI network of merged PPI networks had 164 nodes and 4513 edges. GO and KEGG enrichment analyses showed that triptolide were related to the cell cycle, apoptosis, and inflammatory signaling pathways. Molecular docking analysis showed that triptolide directly reacted with four core targets: cyclin-dependent kinase inhibitor 1A (CDKN1A), c-JUN, RELA, and tumor protein p53 (TP53). CB-Dock analysis indicated that triptolide could stably bind to core targets. Triptolide inhibited the growth but induced apoptosis of thyroid cancer cells. Triptolide increased the mRNA expression of CDKN1A and TP53 but reduced the mRNA expression of c-JUN and RELA, as shown by RT-PCR. Triptolide increased the protein levels of CDKN1A and phospho-p53 but reduced those of phospho-c-JUN and phospho-NF-κB p65, as shown by Western blotting. DISCUSSION: We considered that triptolide could treat thyroid cancer by inhibiting cell proliferation, inducing apoptosis and inhibiting inflammatory pathways such as the NF-κB and MAPK signaling pathways. CDKN1A, c-JUN, RELA, and TP53 were involved in the antithyroid cancer mechanism of triptolide.