Value of serum miR-599 combined with VEGF in predicting recurrence of patients with differentiated thyroid cancer after subtotal resection

doi:10.3760/cma.j.issn.1007-1245.2024.13.020

Abstract

Abstract:

Objective　To investigate the efficacy of serum microRNA-599 (miR-599) and vascular endothelial growth factor (VEGF) levels in the prediction of recurrence of patients with differentiated thyroid cancer (DTC) after totally endoscopic subtotal thyroidectomy. Methods　A total of 135 patients with DTC who underwent totally endoscopic subtotal thyroidectomy at Tongchuan People's Hospital from January 2017 to March 2022 were selected. The serum levels of miR-599 and VEGF in all the patients were detected before the operation. Their preoperative clinical data were collected. The patients were followed up for 2 years after the operation. According to the postoperative recurrence, they were divided into a recurrence group (31 cases) and a non-recurrence group (104 cases). There were 12 men and 19 women in the recurrence group; they were (51.26±7.32) years old. There were 48 men and 56 women in the non-recurrence group; they were (49.57±7.08) years old. The count data were analyzed by χ² test or Fisher's exact probability test. The measurement data were analyzed by the independent-sample t test. The influencing factors of postoperative recurrence were analyzed by the multivariate stepwise logistic regression model. The predictive efficacies of serum miR-599 and VEGF levels in predicting postoperative recurrence were analyzed by the areas (AUC) under the receiver operating characteristic curves (ROC). Results　The level of miR-599 in the recurrence group was lower than that in the non-recurrence group [(0.81±0.09) vs. (1.05±0.12)], and the level of VEGF in the recurrence group was higher than that in the non-recurrence group [(32.55±5.26) ng/L vs. (24.83±4.07) ng/L] (t=10.295 and 8.639; both P<0.001). The proportion of the patients of Ⅲ-Ⅳstage [67.74% (21/31) vs. 28.85% (30/104)] and anti-thyroglobulin antibody (TgAb) level [(251.86±27.98) IU/ml vs. (211.43±23.49) IU/ml] in the recurrence group were higher than those in the non-recurrence groupm, and the proportions of the patients taking intraoperative lymph node dissection [22.58% (7/31) vs. 44.23% (46/104)] and postoperative radioactive iodine therapy [32.26% (10/31) vs. 53.85% (56/104)] in the recurrence group were lower than those in the non-recurrence group (t=8.040; χ²=4.694 and 4.454; all P<0.05). The multivariate stepwise logistic regression analysis showed that the level of miR-599 (OR=0.251, 95%CI 0.109-0.576) was an independent protective factor for postoperative recurrence, and the level of VEGF (OR=2.163, 95%CI 1.256-3.722), clinical stage (OR=4.287, 95%CI 1.908-9.631), and TgAb level (OR=4.612, 95%CI 2.172-9.789) were independent risk factors for postoperative recurrence (all P<0.05). The ROC showed that the sensitivities of miR-599, VEGF, and their combination in the prediction of postoperative recurrence were 71.00%, 74.20%, and 90.30%, respectively; the specificities were 76.90%, 72.10%, and 88.50%, respectively; the AUC's were 0.824, 0.794, and 0.931, respectively (all P<0.05). Conclusions　Serum VEGF level is an independent risk factor for recurrence, and serum miR-599 level is an independent protective factor for recurrence in DTC patients after total endoscopic subtotal thyroidectomy. The combined detection of the two markers can better predict the risk of postoperative recurrence.

Key words:

Differentiated thyroid cancer, MicroRNA-599, Vascular endothelial growth factor, Totally endoscopic subtotal thyroidectomy, , Postoperative recurrence, Prediction efficacy

摘要：

目的　分析血清微RNA-599（miR-599）联合血管内皮生长因子（VEGF）水平对分化型甲状腺癌（DTC）患者全腔镜甲状腺次全切除术后复发的预测效能。方法　选取铜川市人民医院2017年1月至2022年3月收治的行全腔镜甲状腺次全切除术的DTC患者135例。患者术前均检测血清miR-599和VEGF水平，并收集患者术前临床相关资料。术后对患者进行为期2年的随访，根据术后复发情况将其分为复发组（31例）和无复发组（104例）。复发组男12例，女19例，年龄（51.26±7.32）岁；无复发组男48例，女56例，年龄（49.57±7.08）岁。计数资料采用χ²检验或Fisher精确概率检验；计量资料采用独立样本t检验。患者术后复发的影响因素用多因素逐步logistic回归模型进行分析；血清miR-599联合VEGF水平预测患者术后复发的效能用受试者操作特征曲线（ROC）下面积（AUC）进行分析。结果　复发组miR-599水平低于无复发组［（0.81±0.09）比（1.05±0.12）］，VEGF水平高于无复发组［（32.55±5.26）ng/L比（24.83±4.07）ng/L］（t=10.295、8.639，均P<0.001）。复发组Ⅲ～Ⅳ期占比［67.74%（21/31）比28.85%（30/104）］、抗甲状腺球蛋白抗体（TgAb）水平［（251.86±27.98）IU/ml比（211.43±23.49）IU/ml］高于无复发组，术中淋巴结清扫占比［22.58%（7/31）比44.23%（46/104）］、术后放射碘治疗占比［32.26%（10/31）比53.85%（56/104）］低于无复发组（t=8.040，χ²=4.694、4.454，均P<0.05）。多因素逐步logistic回归分析显示，miR-599水平（OR=0.251，95%CI 0.109～0.576）是患者术后复发的独立保护因素，VEGF水平（OR=2.163，95%CI 1.256～3.722）、临床分期（OR=4.287，95%CI 1.908～9.631）、TgAb水平（OR=4.612，95%CI 2.172～9.789）是患者术后复发的独立危险因素（均P<0.05）。ROC显示，miR-599、VEGF及二者联合预测患者术后复发的灵敏度分别为71.00%、74.20%、90.30%，特异度分别为76.90%、72.10%、88.50%，AUC分别为0.824、0.794、0.931（均P<0.05）。结论　血清VEGF水平是DTC患者全腔镜甲状腺次全切除术后复发的独立危险因素，血清miR-599水平是患者术后复发的独立保护因素；二者联合检测可较好地预测患者术后复发风险。

关键词:

分化型甲状腺癌, 微RNA-599, 血管内皮生长因子, 全腔镜甲状腺次全切除术, 术后复发, 预测效能

Yang Kai, Wang Binfeng, Ren Yanshun, Hui Peng.

Value of serum miR-599 combined with VEGF in predicting recurrence of patients with differentiated thyroid cancer after subtotal resection [J]. International Medicine and Health Guidance News, 2024, 30(13): 2219-2224.

杨凯王斌锋任彦顺惠鹏.

血清miR-599联合VEGF预测分化型甲状腺癌患者次全切除术后复发的价值 [J]. 国际医药卫生导报, 2024, 30(13): 2219-2224.

References

[1] Jiang H, Li Y, Shen J, et al. Cigarette smoking and thyroid cancer risk: a Mendelian randomization study [J]. Cancer Med, 2023, 12(19): 19866-19873. DOI: 10.1002/cam4.6570.
[2] Li L, Wang Z, Guo H, et al. Nanomaterials: a promising multimodal theranostics platform for thyroid cancer [J]. J Mater Chem B, 2023, 11(32): 7544-7566. DOI: 10.1039/d3tb01175e.
[3] 王珊珊,戚建国,王洲,等. 超声联合血清VEGF、TSGF检查对分化型甲状腺癌的诊断价值及与临床病理特征的相关性[J]. 川北医学院学报,2022,37(4):437-441. DOI:10.3969/j.issn.1005-3697.2022.04.007.
[4] 潘晓培,钱连连,王慧慧. 改良Miccoli手术治疗分化型甲状腺癌的临床效果及术后复发的相关影响因素[J]. 实用癌症杂志,2023,38(1):73-75. DOI:10.3969/j.issn.1001-5930. 2023.01.020.
[5] 丁斌. 全腔镜甲状腺次全切除术对早期分化型甲状腺癌患者术中切口长度及术后血清Tg、VEGF水平变化的影响[J]. 实用医学杂志,2017,33(21):3581-3584. DOI:10.3969/j.issn.1006-5725.2017.21.021.
[6] 刘延彬,胡瑞丽,李燕萍,等. 分化型甲状腺癌组织中β-连环蛋白和维生素D受体的表达及其与术后复发关系的探讨[J]. 中国耳鼻咽喉颅底外科杂志,2021,27(6):706-711. DOI:10.11798/j.issn.1007-1520.202121001.
[7] Morovat P, Morovat S, Hosseinpour M, et al. Survival-based bioinformatics analysis to identify hub long non-coding RNAs along with lncRNA-miRNA-mRNA network for potential diagnosis/prognosis of thyroid cancer [J]. J Cell Commun Signal, 2023, 17(3): 639-655. DOI: 10.1007/s12079-022-00697-9.
[8] 张学莲,安世芝,杜堂彩,等. miR-599靶向YAP1对卵巢癌细胞迁移及侵袭的影响[J]. 武汉大学学报(医学版),2023,44(8):923-927. DOI:10.14188/j.1671-8852.2022.6004.
[9] 吴岑,郑志雄,黄志扬,等. 微小RNA-599在膀胱癌组织的表达及其临床意义[J]. 中华实验外科杂志,2020,37(2):342-344. DOI:10.3760/cma.j.issn.1001-9030.2020. 02.042.
[10] de Koster EJ, van Engen-van Grunsven ACH, Bussink J, et al. [18F]FDG uptake and expression of immunohistochemical markers related to glycolysis, hypoxia, and proliferation in indeterminate thyroid nodules [J]. Mol Imaging Biol, 2023, 25(3): 483-494. DOI: 10.1007/s11307-022-01776-4.
[11] 陈孝平, 汪建平. 外科学[M]. 8版. 北京:人民卫生出版社, 2013: 244-246.
[12] Gervais HW. The ASA Classification - solid like a rock in anesthesiology [J]. Anaesthesist, 2017, 66(1): 3-4. DOI: 10.1007/s00101-016-0252-6.
[13] Bishop GL, Jasim S, Strnad BS, et al. Papillary thyroid cancer in thyroglossal duct cysts: a pictorial review and case series [J]. Ultrasound Q, 2023, 39(4): 194-198. DOI: 10.1097/RUQ.0000000000000650.
[14] 余江涛,王世杰,张高飞,等. 血清甲状腺球蛋白、促甲状腺激素联合检测对行甲状腺全切术后未接受清甲治疗的分化型甲状腺癌患者复发的预测价值[J]. 实用医学杂志,2023,39(9):1159-1163. DOI:10.3969/j.issn.1006-5725. 2023.09.017.
[15] Zhang J, Ren G, Huang T, et al. miRNA-363-3p hinders proliferation, migration, invasion and autophagy of thyroid cancer cells by controlling SYT1 transcription to affect NF-κB [J]. Endocr Metab Immune Disord Drug Targets, 2024, 24(1): 153-162. DOI: 10.2174/1871530323666230504112553.
[16] Hasbek Z, Taş A, Ertürk SA, et al. Evaluation of the relationship between mobile phone usage and miRNA-574-5p and miRNA-30C-5p levels in thyroid cancer patients [J]. Mol Imaging Radionucl Ther, 2024, 33(1): 19-27. DOI: 10.4274/mirt.galenos.2023.04880.
[17] 马秀丽,刘伟昌,冯园终,等. miR-599和BRD4在卵巢癌中的表达及其与临床病理参数和预后的关系[J]. 中国妇幼保健,2019,34(7):1650-1654. DOI:10.7620/zgfybj.j.issn. 1001-4411.2019.07.63.
[18] Gong YF, Zhang Y, Li LY, et al. Downregulation of miR-599 predicts poor outcome in cervical cancer patients and promotes the progression of cervical cancer [J]. Taiwan J Obstet Gynecol, 2022, 61(2): 249-254. DOI: 10.1016/j.tjog.2021.11.010.
[19] Glasner A, Rose SA, Sharma R, et al. Conserved transcriptional connectivity of regulatory T cells in the tumor microenvironment informs new combination cancer therapy strategies [J]. Nat Immunol, 2023, 24(6): 1020-1035. DOI: 10.1038/s41590-023-01504-2.
[20] Veen T, Kanani A, Lea D, et al. Clinical trials of neoadjuvant immune checkpoint inhibitors for early-stage operable colon and rectal cancer [J]. Cancer Immunol Immunother, 2023, 72(10): 3135-3147. DOI: 10.1007/s00262-023-03480-w.
[21] Hasselluhn MC, Decker-Farrell AR, Vlahos L, et al. Tumor explants elucidate a cascade of paracrine SHH, WNT, and VEGF signals driving pancreatic cancer angiosuppression [J]. Cancer Discov, 2024, 14(2): 348-361. DOI: 10.1158/2159-8290.CD-23-0240.
[22] 孙丹阳,孟召伟,谭建,等. 年龄及甲状腺球蛋白抗体阳性水平对分化型甲状腺癌预后的影响[J]. 中华内分泌代谢杂志,2021,37(12):1068-1074. DOI:10.3760/cma.j.cn311282- 20210225-00121.
[23] 康斗,赵长久. 甲状腺球蛋白抗体(TgAb)在分化型甲状腺癌临床诊疗中应用的研究进展[J]. 现代肿瘤医学,2023,31(17):3330-3334. DOI:10.3969/j.issn.1672-4992.2023. 17.035.
[24] Menon NN, Arora S, Dabas SK, et al. Incidentally detected 131-iodine avid parotid oncocytoma coexistent with papillary carcinoma thyroid [J]. Indian J Otolaryngol Head Neck Surg, 2023, 75(3):2598-2603. DOI: 10.1007/s12070-023-03804-3.