血清中期因子水平对甲状腺乳头状癌术后患者~(131)Ⅰ治疗过程中新发转移的预测价值
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摘要
目的评估血清中期因子(MK)水平对甲状腺乳头状癌(PTC)术后患者~(131)Ⅰ治疗过程中新发转移的预测价值。方法接受甲状腺全切/次全切术和(或)颈部淋巴结清扫术的PTC患者241例,术后实施个体化~(131)Ⅰ治疗。在首次~(131)Ⅰ治疗前(T1)、首次~(131)Ⅰ治疗后10～12个月时(T2),采用MK检测试剂盒检测所有患者的血清MK,分别记为MK1、MK2。根据血清MK2水平将患者分成A、B、C组,血清MK2水平≤正常值上限(508. 57 pg/m L)者为A组,血清MK2水平>正常值上限且≤MK1者为B组,血清MK2水平> MK1>正常值上限者为C组。根据分组结果,比较各组患者T2时新发转移情况。以A组为对照组,采用Cox回归分析法计算B、C组患者新发转移的风险比(HR)和95%置信区间(CI)。结果 241例PTC患者中,55例患者在T2时出现新发转移灶,其中A组11例、B组28例、C组16例,C组患者T2时出现新发转移灶者与A、B组相比,P均<0. 01。Cox回归分析显示,B组患者新发转移的HR为3. 374(P <0. 05,95%CI为1. 328～5. 047),C组患者新发转移的HR为6. 731(P <0. 05,95%CI为3. 121～14. 800)。结论血清MK水平对PTC术后患者~(131)Ⅰ治疗过程中新发转移有一定的预测价值。
Objective To evaluate the predictive value of serum midkine( MK) levels for new metastases during ~(131)Ⅰ ablation treatment in postoperative patients with thyroid papillary carcinoma( PTC). Methods Totally 241 patients with PTC undergoing total thyroidectomy/subtotal resection and/or cervical lymph node dissection were treated with individualized ~(131)Ⅰ ablation. The serum MK concentrations were determined before the first ~(131)Ⅰ ablation treatment( T1) and 10-12 months after the first ~(131)Ⅰ ablation treatment( T2),which were recorded as MK1 and MK2,respectively. According to the serum MK2 level,the patients were divided into groups A [serum MK2 levels less than or equal to the upper limit of normal value( 508. 57 pg/m L) ],B( MK2 levels above the upper limit of normal and less than or equal to MK1),and C( MK2 levels above MK1 and the upper limit of normal value). According to the grouping,the new metastases were compared between the three groups at T2. Cox regression analysis was used to calculate the risk ratio( HR) and 95% confidence interval( CI) for new metastases in patients of groups B and C by taking the group A as the control group. Results Among 241 patients with PTC,new metastases occurred in 55 patients at T2,including 11 patients in the group A,28 patients in the group B,and 16 patients in the group C. The incidence of new metastases at T2 in the group C was higher than that in the groups A and B( P < 0. 01). Cox regression analysis showed that the HR of new metastases in the group B was 3. 374( P< 0. 05,95% CI: 1. 328-5. 047),which was 6. 731 in the group C( P < 0. 05,95% CI: 3. 121-14. 800). Conclusion Serum MK level has certain predictive value for new metastasis during ~(131)Ⅰ ablation treatment for postoperative PTC patients.
Objective To evaluate the predictive value of serum midkine( MK) levels for new metastases during ~(131)Ⅰ ablation treatment in postoperative patients with thyroid papillary carcinoma( PTC). Methods Totally 241 patients with PTC undergoing total thyroidectomy/subtotal resection and/or cervical lymph node dissection were treated with individualized ~(131)Ⅰ ablation. The serum MK concentrations were determined before the first ~(131)Ⅰ ablation treatment( T1) and 10-12 months after the first ~(131)Ⅰ ablation treatment( T2),which were recorded as MK1 and MK2,respectively. According to the serum MK2 level,the patients were divided into groups A [serum MK2 levels less than or equal to the upper limit of normal value( 508. 57 pg/m L) ],B( MK2 levels above the upper limit of normal and less than or equal to MK1),and C( MK2 levels above MK1 and the upper limit of normal value). According to the grouping,the new metastases were compared between the three groups at T2. Cox regression analysis was used to calculate the risk ratio( HR) and 95% confidence interval( CI) for new metastases in patients of groups B and C by taking the group A as the control group. Results Among 241 patients with PTC,new metastases occurred in 55 patients at T2,including 11 patients in the group A,28 patients in the group B,and 16 patients in the group C. The incidence of new metastases at T2 in the group C was higher than that in the groups A and B( P < 0. 01). Cox regression analysis showed that the HR of new metastases in the group B was 3. 374( P< 0. 05,95% CI: 1. 328-5. 047),which was 6. 731 in the group C( P < 0. 05,95% CI: 3. 121-14. 800). Conclusion Serum MK level has certain predictive value for new metastasis during ~(131)Ⅰ ablation treatment for postoperative PTC patients.
引文
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[12]Krzystek-Korpacka M,Diakowska D,Neubauer K,et al. Circulating midkine in malignant and non-malignant colorectal diseases[J]. Cytokine,2013,64(1):158-164.
[13]Zhu WW,Guo JJ,Guo L,et al. Evaluation of midkine as a diagnostic serum biomarker in hepatocellular carcinoma[J]. Clin Cancer Res,2013,19(14):3944-3954.
[14]Shimada H,Nabeya Y,Tagawa M,et al. Preoperative serum midkine concentration is a prognostic marker for esophageal squamous cell carcinoma[J]. Cancer Sci,2003,94(7):628-632.
[2]Cooper DS,Doherty GM,Haugen BR,et al. Revised American thyroid association management guidelines for patients with thyroid nodules and differentiated thyroid cancer[J]. Thyroid,2009,19:1167-1214.
[3]Muramatsu T. Structure and function of midkine as the basis of its pharmacological effects[J]. Br J Pharmacol,2014,171:814-826.
[4]Shao H,Yu X,Wang C,et al. Midkine expression is associated with clinicopathological features and BRAF mutation in papillary thyroid cancer[J]. Endocrine,2014,46(2):285-291.
[5]Jia Q,Meng Z,Xu K,et al. Serum midkine as a surrogate biomarker for metastatic prediction in differentiated thyroid cancer patients with positive thyroglobulin antibody[J]. Sci Rep,2017,7:43516.
[6]Siegel RL,Miller KD,Jemal A. Cancer statistics,2016[J]. CA Cancer J Clin,2016,66(1):7-30.
[7]Haugen BR,Alexander EK,Bible KC,et al. 2015 American thyroid association management guidelines for adult patients with thyroid nodules and differentiated thyroid ancer:the American thyroid association guidelines task force on thyroid nodules and differentiated thyroid cancer[J]. Thyroid,2016,26(1):1-133.
[8]Gadawska-Juszczyk K,Kowalska A. Comparison of the usefulness of post-ablative and post-operative thyroglobulin concentration measuring in prognostic assessment of patients with differentiated thyroid cancer[J]. Endokrynol Pol,2015,66(6):486-494.
[9]Leung AM,Dave S,Lee SL,et al. Factors determining the persistence or recurrence of well-differentiated thyroid cancer treated by thyroidectomy and/or radioiodine in the Boston,Massachusetts area:A retrospective chart review[J]. Thyroid res,2011,4(1):9.
[10]Spencer C,Fatemi S. Thyroglobulin antibody(Tg Ab)methodsStrengths,pitfalls and clinical utility for monitoring Tg Ab-positive patients with differentiated thyroid cancer[J]. Best Pract Res Clin Endocrinol Metab,2013,27(5):701-712.
[11]Kadomatsu K,Tomomura M,Muramatsu T. c DNA cloning and sequencing of a new gene intensely expressed in early differentiation stages of embryonal carcinoma cells and in mid-gestation period of mouse embryogenesis[J]. Biochem Biophys Res Commun,1988,151(3):1312-1318.
[12]Krzystek-Korpacka M,Diakowska D,Neubauer K,et al. Circulating midkine in malignant and non-malignant colorectal diseases[J]. Cytokine,2013,64(1):158-164.
[13]Zhu WW,Guo JJ,Guo L,et al. Evaluation of midkine as a diagnostic serum biomarker in hepatocellular carcinoma[J]. Clin Cancer Res,2013,19(14):3944-3954.
[14]Shimada H,Nabeya Y,Tagawa M,et al. Preoperative serum midkine concentration is a prognostic marker for esophageal squamous cell carcinoma[J]. Cancer Sci,2003,94(7):628-632.