Analysis Of Surgical Strategy For Early Stages Of Thyroid Cancer And The Analysis Of DUXAP8 Expression In Patients With Different N Stages

[Objective]To optimize thyroid carcinoma surgery principles:To explore the feasibility and rationality of lobectomy in the treatment of pediatric thyroid papillary carcinoma(PTC)with low-intermediate risk;to determine the predictive ability of multifocality for central lymph node metastasis in initially treated 18-55 years old female patients with unilateral papillary thyroid microcarcinoma;to determine the predictive ability of preoperative blood serum calcitonin(Ctn)level for lateral neck lymph node metastasis(LLNM)in initially treated medullary thyroid cancer(MTC)patients and discuss surgery strategy of prophylactic lateral neck dissection;to explore the association of DUXAP8 expression and lateral lymph node metastasis in papillary thyroid cancer.[Methods]1.The clinicopathological features and follow-up data of pediatric PTC with low-intermediate risk were reviewed from March 2000 to December 2018 in Cancer Hospital of Chinese Academy of Medical Sciences.The correlations between different surgical procedures and prognoses were evaluated.Propensity score matching(PSM)was used to adjust for risk factors,and the difference in prognoses between the total thyroidectomy(TT)group and the lobectomy(LT)group was compared.2.Total 975 initially treated 18-55 years old female patients with unilateral papillary thyroid microcarcinoma between January 1st,2018,and December 31st,2018,was collected.Clinicopathological factors associated with central lymph node metastasis were investigated by univariate and multivariate analysis.3.Data from initially treated MTC patients at our institution between 2010 and 2021 was collected.Demographics,clinical,imaging,and pathological findings were analyzed.We stratified the cohort into three subgroups according to the maximum ultrasound diameter of the primary tumor(t).We combined pathological and follow-up results to diagnose preoperative lateral lymph node metastases.Receiver operating characteristic(ROC)analysis was performed to test the predictive performance of pre-Ctn for LLNM.Youden’s Index was calculated for cutpoint analysis to determine optimal cutpoint to perform PLND.4.Public data from TCGA was collected.Data that includes sample gene expression,clinical and pathological characteristics,and survival data,were integrated,and analyzed using R language to explore whether DUXAP8 is correlated with the occurrence and development of papillary thyroid cancer.The expression level of DUXAP8 in clinical specimens was detected by real-time quantitative fluorescence polymerase chain reaction(RT-qPCR).The clinicopathologic features and DUXAP8 expression levels of patients in the cohort were compared by statistical analysis.[Results]1.A total of 140 patients were included in the study,including 36 males and 104 females.The age range was from 6-year-old to 18-year-old.There were 43 low-risk patients and 97 intermediate-risk patients.The median follow-up time was 87.5 months,ranging from 8 to 241 months,and 20 patients(14.3%)showed recurrence during the follow-up period.Univariate analysis showed that NIb,extrathyroidal extension,the number of lymph node metastasis>5,the ratio of lymph node metastasis≥0.19,and radioactive iodine treatment were risk factors for recurrence(all P value below 0.05),but multivariate analysis showed that only the ratio of lymph node metastasis≥0.19(HR=8.69,95%CI:1.08-70.21,P=0.043)was an independent risk factor for recurrence.There was no significant difference in the 5-year recurrence free survival rates between TT group and LT group before propensity score matching(82.8%vs.86.5%,χ2=0.219,P=0.640)and after propensity score matching(89.6%vs.90.4%,χ2=0.099,P=0.753).2.Total 196(20.1%)patients were multifocal,including 126(12.9%)with 2 lesions and 70(7.2%)with more than 2 lesions.The risk of central lymph node metastasis in patient with 1 lesion was not significantly different from patients with 2 lesions(38.6%vs 37.3%,P=0.775).However,multifocality with over 2 lesions was an independent risk factor for central lymph node metastasis(OR=3.271,95%CI:1.951-5.482,P<0.001).Maximum diameter over 0.5cm was a significant risk factor for central lymph node metastasis(OR=2.047,95%CI:1.535-2.730,P<0.001).3.A total of 94 patients were included.Pre-Ctn>326.7 pg/mL and pre-Ctn>1336.5 pg/mL was a risk factor for patients with t≤2cm(OR=6.682,95%CI:1.654-26.998,P=0.012)and 2cm ＜t≤4cm(OR=11.143,95%CI:1.108-112.012,P=0.033)respectively.4.Public data analysis shows that DUXAP8 expression was correlated with age,T stage and lymph node metastatic in PTC patients.DUXAP8 expression was higher in patients with higher T stage and N stage.Data analysis of our own specimens shows that DUXAP8 expression was higher in patients with lateral neck metastasis,which was consistent with the results of bioinformation analysis.[Conclusion]1.Lobectomy is feasible for selective pediatric PTC with low-intermediate risk.2.Multifocality in initially treated 18-55 years old female patients with unilateral papillary thyroid microcarcinoma should not be simply defined as over 1 focus.3.For patients with t ≤2cm and pre-Ctn≤326.7 pg/mL,PLND is not recommended.4.High expression of DUXAP8 is associated with invasive biology behaviors in patients with PTC.