临床病理特征联合基因检测预测甲状腺微小乳头状癌隐匿性淋巴结转移的临床应用

doi:10.3969/j.issn.1006-5725.2025.22.015

Abstract

Abstract:

Objective To investigate the predictive value of integrating clinical pathological characteristics with genetic testing for occult lymph node metastasis （OLNM） in patients with papillary thyroid microcarcinoma （PTMC）. Methods A total of 104 PTMC patients admitted to our hospital between May 2023 and May 2025 were included in the study. All patients showed no evidence of suspicious lymph node metastasis on preoperative imaging and underwent standard thyroidectomy with central lymph node dissection. Based on postoperative pathological confirmation of central lymph node metastasis status， patients were classified into an OLNM-positive group （n = 53） and an OLNM-negative group （n = 51）. Baseline characteristics， clinicopathological features， BRAF^V600E gene mutation status， and TERT promoter mutation status were compared between the two groups. To identify factors independently associated with OLNM in PTMC patients， multivariate logistic regression analysis was conducted. The area under the receiver operating characteristic curve （AUC） was utilized to assess the predictive performance of a combined model incorporating clinical， pathological， and genetic features for OLNM. Results Compared with the OLNM-negative group， the OLNM-positive group exhibited significantly higher preoperative thyroid-stimulating hormone （TSH） levels （P < 0.05）. Moreover， the OLNM-positive group demonstrated significantly greater proportions of tumors with diameter > 0.5 cm， multifocality， microcalcifications， capsule invasion， extrathyroidal extension， T3 stage， BRAF^V600E mutation， and TERT promoter mutation （all P < 0.05）. Multivariate logistic regression analysis identified preoperative TSH level， tumor diameter > 0.5 cm， multifocal lesions， capsule invasion， extrathyroidal extension， T stage， BRAF^V600E mutation， and TERT promoter mutation as independent risk factors for OLNM in patients with PTMC （all P < 0.05）. ROC curve analysis demonstrated that the integrated model combining clinical pathological features?including tumor diameter， number of lesions， microcalcification， capsule invasion， extrathyroidal extension， and T stage?with genetic markers （BRAF^V600E and TERT promoter mutations） exhibited the highest predictive performance， yielding an AUC of 0.940. This was significantly higher than the model based solely on clinical pathological features （AUC = 0.736） or those relying exclusively on genetic testing （BRAF^V600E： AUC = 0.860； TERT： AUC = 0.882）， with all comparisons reaching statistical significance （P < 0.05）. Conclusions The integration of clinical pathological features with genetic testing significantly improved the predictive accuracy of OLNM in PTMC patients， surpassing models based solely on individual clinical pathological characteristics or genetic tests alone. This multimodal strategy offers a robust， evidence-based foundation for personalized surgical planning and enhances the precision of clinical decision-making in the management of PTMC.

Key words: papillary thyroid microcarcinoma, occult lymph node metastasis, clinical pathological features, genetic testing, predictive value

CLC Number:

R736.1

Jixin CHAI,Yong CHEN,Xue ZHANG,Yazhou AO,Bo. LI. Clinical application of combined clinical pathological features and genetic testing in predicting occult lymph node metastasis in patients with papillary thyroid microcarcinoma[J]. The Journal of Practical Medicine, 2025, 41(22): 3572-3578.

Figures/Tables 6

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References 29

[1]	MIYAUCHI A， ITO Y， FUJISHIMA M， et al. Long-term outcomes of active surveillance and immediate surgery for adult patients with low-risk papillary thyroid microcarcinoma： 30-year experience［J］. Thyroid， 2023， 33（7）： 817-825. doi:10.1089/thy.2023.0076 doi: 10.1089/thy.2023.0076
[2]	CHEN Z， ZHANG W， HE W， et al. Ultrasound-guided thermal ablation for papillary thyroid microcarcinoma： A systematic review［J］. Clin Endocrinol （Oxf）， 2023， 98（3）： 296-305. doi:10.1111/cen.14857 doi: 10.1111/cen.14857
[3]	WANG J， FU W， LUO J， et al. Development of a clinical-molecular prediction model for central lymph node metastasis in cN0 stage papillary thyroid microcarcinoma： A retrospective study［J］. BMC Cancer， 2025， 25（1）： 693. doi:10.1186/s12885-025-14112-0 doi: 10.1186/s12885-025-14112-0
[4]	刘津，王小平，瞿琳娣，等. 热消融技术治疗甲状腺微小乳头状癌的研究进展［J］. 西安交通大学学报（医学版）， 2024， 45（6）： 1041-1046.
[5]	许魁，周军. 超声微泡在甲状腺癌诊疗中的研究进展［J］. 实用医学杂志， 2025， 41（3）： 454-458.
[6]	ZHANG J， YI W， WU R， et al. Predictive nomogram for occult metastasis in central lymph nodes of papillary thyroid microcarcinoma based on clinical and ultrasound features［J］. Gland Surg， 2025， 14（7）： 1295-1305. doi:10.21037/gs-2025-159 doi: 10.21037/gs-2025-159
[7]	HUANG X， HUANG X， WANG K， et al. Predictors of occult lymph node metastasis in clinical T1 lung adenocarcinoma： A retrospective dual-center study［J］. BMC Pulm Med， 2025， 25（1）： 99. doi:10.1186/s12890-025-03559-3 doi: 10.1186/s12890-025-03559-3
[8]	REN J， YUAN Y， TAO X， et al. Histogram analysis of diffusion-weighted imaging and dynamic contrast-enhanced MRI for predicting occult lymph node metastasis in early-stage oral tongue squamous cell carcinoma［J］. Eur Radiol， 2022， 32（4）： 2739-2747. doi:10.1007/s00330-021-08310-0 doi: 10.1007/s00330-021-08310-0
[9]	张洁，冯艳红，何秀丽，等. 常规超声特征及BRAFV600E基因突变与甲状腺乳头状癌中央区淋巴结转移的相关性［J］. 临床耳鼻咽喉头颈外科杂志， 2022， 36（3）： 184-188.
[10]	SAKO A， MATSUSE M， SAENKO V， et al. TERT promoter mutations increase tumor aggressiveness by altering TERT mRNA splicing in papillary thyroid carcinoma［J］. J Clin Endocrinol Metab， 2024， 109（10）： e1827-e1838. doi:10.1210/clinem/dgae220 doi: 10.1210/clinem/dgae220
[11]	赵雯，董珍林，单海燕，等. 双能CT碘图预测甲状腺乳头状癌颈部中央区隐匿性淋巴结转移的价值［J］. 中国医学影像学杂志， 2023， 31（10）： 1007-1010， 1023.
[12]	KUMAR R， MANCHANDA S， HOTA A， et al. Ultrasound characteristics of metastatic occult cervical lymph nodes in early tongue cancer［J］. Indian J Otolaryngol Head Neck Surg， 2023， 75（4）： 2786-2791. doi:10.1007/s12070-023-03881-4 doi: 10.1007/s12070-023-03881-4
[13]	XUE B， WANG X， et al. Predictive value of PET metabolic parameters for occult lymph node metastases in PET/CT defined node-negative patients with advanced epithelial ovarian cancer［J］. Sci Rep， 2023， 13（1）： 9439. doi:10.1038/s41598-023-36640-0 doi: 10.1038/s41598-023-36640-0
[14]	HU R， REN Q， LI T， et al. Evidence-based integration of clinicopathological factors with the risk of papillary thyroid carcinoma lateral cervical lymph node metastasis： Systematic review and meta-analysis and subgroup study［J］. Gland Surg， 2025， 14（5）： 912-928. doi:10.21037/gs-2025-60 doi: 10.21037/gs-2025-60
[15]	ZENG S， HU H， LI Z， et al. Local TSH/TSHR signaling promotes CD8⁺ T cell exhaustion and immune evasion in colorectal carcinoma［J］. Cancer Commun （Lond）， 2024， 44（11）： 1287-1310. doi:10.1002/cac2.12605 doi: 10.1002/cac2.12605
[16]	WU Z， XI Z， XIAO Y， et al. TSH-TSHR axis promotes tumor immune evasion［J］. J Immunother Cancer， 2022， 10（1）： e004049. doi:10.1136/jitc-2021-004049 doi: 10.1136/jitc-2021-004049
[17]	董萌，洪晨忱，聂昕玥，等. cN0期甲状腺乳头状癌右喉返神经深层淋巴结转移的影响因素及预测模型构建［J］. 中国普通外科杂志， 2023， 32（5）： 673-681.
[18]	CHANG J， SARASWATHIBHATLA A， SONG Z， et al. Cell volume expansion and local contractility drive collective invasion of the basement membrane in breast cancer［J］. Nat Mater， 2024， 23（5）： 711-722. doi:10.1038/s41563-023-01716-9 doi: 10.1038/s41563-023-01716-9
[19]	徐泽林，郑振浩，邓雅倩，等. 弹性相对指数联合S-Detect对甲状腺乳头状癌颈部淋巴结转移的预测价值［J］. 实用医学杂志， 2025， 41（16）： 2581-2589.
[20]	贺星云，刘晨，杜俊泽，等. 基于增强静脉期CT放射组学的甲状腺乳头状癌中央区淋巴结转移预测模型构建与验证［J］. 陆军军医大学学报， 2025， 47（12）： 1367-1375.
[21]	张继方，陈芳，唐佳雯，等. 肿瘤出芽及肿瘤浸润淋巴细胞对食管鳞状细胞癌淋巴结转移的预测价值研究［J］. 中国全科医学， 2023， 26（32）： 4038-4042.
[22]	张浩轩，陆进，蒋成义，等. 基于人工智能技术的鼻咽癌风险预测模型的构建与评价［J］. 南方医科大学学报， 2023， 43（2）： 271-279. doi:10.12122/j.issn.1673-4254.2023.02.16 doi: 10.12122/j.issn.1673-4254.2023.02.16
[23]	GADAL S， BOYER J A， ROY S F， et al. Tumorigenesis driven by BRAFV600E requires secondary mutations that overcome its feedback inhibition of RAC1 and migration［J］. Cancer Res， 2025， 85（9）： 1611-1627. doi:10.1158/0008-5472.can-24-2220 doi: 10.1158/0008-5472.can-24-2220
[24]	LI S， XUE J， JIANG K， et al. TERT promoter methylation is associated with high expression of TERT and poor prognosis in papillary thyroid cancer［J］. Front Oncol， 2024， 14： 1325345. doi:10.3389/fonc.2024.1325345 doi: 10.3389/fonc.2024.1325345
[25]	PARVATHAREDDY S K， SIRAJ A K， IQBAL K， et al. TERT promoter mutations are an independent predictor of distant metastasis in Middle Eastern papillary thyroid microcarcinoma［J］. Front Endocrinol （Lausanne）， 2022， 13： 808298. doi:10.3389/fendo.2022.808298 doi: 10.3389/fendo.2022.808298
[26]	TRAVAGLINO A， RAFFONE A， SANTORO A， et al. Clinicopathological features associated with microsatellite instability/mismatch repair deficiency in uterine carcinosarcoma： A quantitative systematic review［J］. Pathobiology， 2022， 89（4）： 198-204. doi:10.1159/000521876 doi: 10.1159/000521876
[27]	TANG L， ZHU Y， DU Y， et al. Clinicopathologic features and genomic profiling of female axillary lymph node metastases from adenocarcinoma or poorly differentiated carcinoma of unknown primary［J］. J Cancer Res Clin Oncol， 2024， 150（5）： 256. doi:10.1007/s00432-024-05783-6 doi: 10.1007/s00432-024-05783-6
[28]	MA D， ZHANG Y， SHAO X， et al. PET/CT for predicting occult lymph node metastasis in gastric cancer［J］. Curr Oncol， 2022， 29（9）： 6523-6539. doi:10.3390/curroncol29090513 doi: 10.3390/curroncol29090513
[29]	SEOL H Y， KIM Y S， KIM S J， et al. Predictive value of 18F-fluorodeoxyglucose positron emission tomography or positron emission tomography/computed tomography for assessment of occult lymph node metastasis in non-small cell lung cancer［J］. Oncology， 2021， 99（2）： 96-104. doi:10.1159/000509988 doi: 10.1159/000509988

目的基因	引物名称	引物序列（5′→3′）	片段长度/bp	退火温度/℃
BRAF	BRAF-^V600E-F	TCATAATGCTTGCTCTGATAGGA	150	60
BRAF	BRAF-^V600E-R	GGCCAAAAATTTAATCAGTGGA	150	60
TERT	TERT-C228T-F	GCCCTGACGTCTGGCTTC	178	60
TERT	TERT-C250T-R	GGCGGCCGGAAAGGGAT	178	60

项目	OLNM阳性组（n = 53）	OLNM阴性组（n = 51）	χ²/t值	P值
年龄/岁	44.32 ± 8.76	46.18 ± 9.24	1.054	0.295
性别/［例（%）］			0.143	0.704
男	12（22.64）	10（19.61）
女	41（77.36）	41（80.39）
体质量指数/（kg/m²）	23.87 ± 3.15	24.02 ± 2.97	0.249	0.803
合并结节性甲状腺肿/［例（%）］	19（35.85）	17（33.33）	0.072	0.787
吸烟史/［例（%）］?	?9（16.98）	6（11.76）	0.573	0.449
术前FT3/（pmol/L）?	4.82 ± 0.67	4.91 ± 0.59	0.725	0.469
术前FT4/（pmol/L）?	15.34 ± 2.16	15.87 ± 1.95	1.311	0.192
术前TSH/（μIU/mL）	2.83 ± 1.24	2.05 ± 0.91	3.645	< 0.001

项目	OLNM阳性组（n = 53）	OLNM阴性组（n = 51）	χ² 值	P值
肿瘤最大径			4.776	0.028
0.5 ~ 1.0 cm	39（73.58）	27（52.94）
< 0.5 cm	14（26.42）	24（47.06）
病灶数			5.877	0.015
单发	25（47.17）	36（70.59）
多发	28（52.83）	15（29.41）
微钙化			8.657	0.003
是	34（64.15）	18（35.29）
否	19（35.85）	33（64.71）
被膜侵犯			13.099	< 0.001
是	31（58.49）	12（23.53）
否	22（41.51）	39（76.47）
侵及腺外			6.784	0.009
是	19（35.85）	7（13.73）
否	34（64.15）	44（86.27）
T分期			5.829	0.015
T1a	35（66.04）	44（86.27）
T3	18（33.96）	7（13.73）
BRAF^V600E突变			5.278	0.021
是	47（88.68）	36（70.59）
否	6（11.32）	15（29.41）
TERT启动子突变			10.630	0.001
是	18（33.96）	4（7.84）
否	35（66.04）	47（92.16）

项目	赋值	β	S.E	Wald χ²	P值	OR	OR（95%CI）
术前TSH	连续变量	0.427	0.152	7.892	0.005	1.533	1.137 ~ 2.066
肿瘤最大径	1 = 0.5 ~ 1.0 cm，0 =?< 0.5 cm	1.012	0.412	6.036	0.014	2.752	1.227 ~ 6.172
病灶数	1=多发，0 =单发	0.836	0.398	4.412	0.036	2.307	1.056 ~ 5.041
微钙化	1 =是，0 =否	0.725	0.385	3.552	0.059	2.064	0.972 ~ 4.384
被膜侵犯	1 =是，0 =否	1.352	0.431	9.837	0.002	3.867	1.662 ~ 9.001
侵及腺外	1 =是，0 =否	1.098	0.462	5.649	0.017	3.001	1.213 ~ 7.421
T分期	1 = T3，0 =T1a	1.504	0.512	8.631	0.003	4.502	1.651 ~ 6.269
BRAF^V600E突变	1 =是，0 =否	0.875	0.542	2.610	< 0.001	2.399	1.830 ~ 6.938
TERT启动子突变	1 =是，0 =否	1.792	0.602	8.861	0.003	6.015	1.842 ~ 8.545

变量	AUC	95%CI	灵敏度/%	特异度/%	P值
临床病理特征模型	0.736	0.629 ~ 0.843	72.53	65.84	< 0.001
BRAF^V600E突变	0.860	0.771 ~ 0.949	85.64	75.46	< 0.001
TERT启动子突变	0.882	0.808 ~ 0.956	90.25	80.64	< 0.001
联合检测	0.940	0.892 ~ 0.987	95.10	90.21	< 0.001

Clinical application of combined clinical pathological features and genetic testing in predicting occult lymph node metastasis in patients with papillary thyroid microcarcinoma

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