<i>FGFR3</i>和<i>TERT</i>基因突变与尿道上皮细胞癌病理分级相关性研究

任莹; 何喻; 李萍

doi:10.16766/j.cnki.issn.1674-4152.003871

FGFR3和TERT基因突变与尿道上皮细胞癌病理分级相关性研究

doi: 10.16766/j.cnki.issn.1674-4152.003871

宁波大学附属人民医院病理科，浙江宁波 315040

基金项目:

浙江省医药卫生科技计划项目 2023KY1146

详细信息

通讯作者:
任莹，E-mail：renying2023@126.com

中图分类号: R737.1 R730.43
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- 文章访问数: 8
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- 被引次数: 0
出版历程
- 收稿日期: 2024-03-18
- 网络出版日期: 2025-03-27

A study on the correlation between FGFR3 and TERT gene mutations and the pathological grade of urethral epithelial carcinoma

Department of Pathology, the Affiliated People ' s Hospital of Ningbo University, Ningbo, Zhejiang 315040, China

摘要

摘要: 目的探讨FGFR3和TERT基因突变与尿道上皮细胞癌病理分级的相关性, 为探索该病发病机制提供一定的参考。方法选取2021年1月-2023年3月在宁波大学附属人民医院泌尿外科门诊就诊和住院治疗的尿路上皮癌患者150例为研究对象, 选择15例健康体检者为对照组。提取所有患者尿液中细胞基因组DNA, 以Real-time PCR检测其FGFR3和TERT基因多态性, 并探讨与其细胞病理诊断分级的关系。结果实验组标本的FGFR3基因外显子7、10和15 DNA含量均高于对照组(P < 0.05);HIT组(T1, T2, T3, T4和Tis)的结果高于LIT组(Ta, P < 0.05);实验组内随着细胞恶性程度的升高细胞内FGFR3基因外显子7、10和15 DNA含量逐渐增高; TERT启动子的2个热点突变C228T和C250T在实验组中不同病理学分级的野生型占比随着肿瘤恶性程度的升高逐渐下降: Ta (5/8, 62.5%), T1(11/29, 37.9%), T2(9/40, 22.5%), T3(7/28, 25.0%), T4(7/27, 25.9%)和Tis (4/18, 22.2%); HIT组(T1, T2, T3, T4和Tis)均出现了C228T突变, C250T突变和C228T+C250T双突变。结论细胞基因组FGFR3基因外显子7、10和15 DNA含量和TERT启动子的C228T和C250T多态性与尿道上皮细胞癌病理分级相关, 可作为尿道上皮细胞癌病理分级的生物标志物。
- 尿路上皮癌 /
- FGFR3 /
- TERT /
- 基因突变 /
- 预后
Abstract: Objective To investigate the correlation between FGFR3and TERT gene mutations and the pathological grade of urethral epithelial carcinoma, aims to provide some reference for exploring the publication mechanism of the disease. Methods A total of 150 patients with urothelial carcinoma hospitalized in the department of Urology at the Affiliated People's Hospital of Ningbo University from January 2021 to March 2023 were selected as the study subjects.Fifteen healthy subjects were selected as the control group.Genomic DNA was extracted, and FGFR3 and TERT gene polymorphisms were analyzed by real-time PCR.The relationship between the cytopathological diagnostic grade was explored. Results The DNA content of FGFR3 exons 7, 10, and 15 was higher in the experimental group than the control group (P < 0.05).The HIT group (T1, T2, T3, T4, and Tis) showed higher DNA content than the LIT group (Ta, P < 0.05).The DNA content of FGFR3 exons 7, 10, and 15 increased gradually with rising tumor malignancy in the experimental group.For the TERT promoter, the proportion of wild type in C228T and C250T polymorphisms decreased as tumor malignancy increased: Ta (5/8, 62.5%), T1(11/29, 37.9%), T2(9/40, 22.5%), T3(7/28, 25.0%), T4(7/27, 25.9%), and Tis (4/18, 22.2%).The HIT group (T1, T2, T3, T4 and Tis) showed C228T mutations, C250T mutations, and C228T+C250T double mutations. Conclusion The DNA content of FGFR3 exons 7, 10, and 15, along with the C228T and C250T polymorphisms of the TERT promoter, correlates with the pathological grade of urothelial carcinoma pathological grade.These markers can be used as biomarkers for assessing pathological grade of urothelial carcinoma.
- Urothelial carcinoma /
- FGFR3 /
- TERT /
- Gene mutation /
- Prognosis

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图 1 手术标本的组织病理图(HE染色，×200)

注：A为良性尿路上皮癌，B为低级别尿路上皮癌，C为高级别尿路上皮癌。

Figure 1. Histopathological map of surgical specimens (HE staining, ×200)

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表 1 150例尿路上皮癌患者的病理诊断结果(例)

Table 1. Pathological diagnosis results of 150 patients with urothelial carcinoma (cases)

类别	男性			女性
类别	40~49岁	50~59岁	≥60岁	40~49岁	50~59岁	≥60岁
Ta	2	2	1	0	1	2
T1	1	6	6	3	8	5
T2	7	11	12	3	3	4
T3	3	9	11	1	1	3
T4	4	11	6	1	4	1
Tis	3	1	12	0	1	1

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表 2 对照组及不同病理级别癌细胞中FGFR3基因外显子7、10和15 DNA含量比较(x±s)

Table 2. Comparison of DNA content in exons 7, 10, and 15 of the FGFR3 gene between the control group and cancer cells of different pathological grades(x±s)

组别	类别	例数	外显子7	外显子10	外显子15
对照组		15	0.32±0.12	0.19±0.11	0.20±0.10
实验组	Ta	8	0.54±0.11^a	0.29±0.12^a	0.27±0.09^a
	T1	29	0.71±0.13^ab	0.84±0.10^ab	0.67±0.11^ab
	T2	40	0.92±0.08^ab	0.99±0.18^ab	0.84±0.12^ab
	T3	28	0.89±0.17^ab	1.66±0.13^ab	1.56±0.15^ab
	T4	27	1.54±0.15^ab	1.57±0.18^ab	1.71±0.13^ab
	Tis	18	1.91±0.21^ab	2.04±0.23^ab	1.98±0.19^ab
F值			290.018	326.306	531.053
P值			< 0.001	< 0.001	< 0.001
注: 与对照组比较, ^aP < 0.05；与Ta比较, ^bP < 0.05。

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表 3 TERT基因多态性检测结果[例(%)]

Table 3. Results of TERT gene polymorphism detection[cases (%)]

组别	类别	例数	野生型	C228T	C250T	C228T+C250T
对照组		15	14(93.3)	0	1	0
实验组	Ta	8	5(62.5)	3(37.5)	1(12.5)	0
	T1	29	11(37.9)	18(62.1)	9(31.0)	9(31.0)
	T2	40	9(22.5)	20(50.0)	16(40.0)	15(37.5)
	T3	28	7(25.0)	21(75.0)	17(60.7)	10(35.7)
	T4	27	7(25.9)	19(70.4)	20(74.1)	18(66.7)
	Tis	18	4(22.2)	13(72.2)	14(77.8)	13(72.2)
F值			21.010	19.591	39.954	37.794
P值			< 0.001	< 0.001	< 0.001	< 0.001

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参考文献(16)

[1]	周晓蝶, 陈巍魏, 余波, 等. 尿路上皮癌的临床病理学特征[J]. 诊断学理论与实践, 2023, 22(3): 292-299. ZHOU X D, CHEN W W, YU B, et al. Clinicopathological features of urothelial carcinoma[J]. Diagnostic theory and practice, 2023, 22(3): 292-299.
[2]	BAROCAS D A, BOORJIAN S A, ALVAREZ R D, et al. Microhematuria: AUA/SUFU guideline[J]. J Urol, 2020, 204(4): 778-786.
[3]	BERTZ S, STOHR R, GAISA N T, et al. TERT promoter mutation analysis as a surrogate to morphology and immunohistochemistry in problematic spindle cell lesions of the urinary bladder[J]. Histopathology, 2020, 77(6): 949-962.
[4]	薛立芝, 谭焕腾, 张思泉, 等. 成纤维细胞生长因子21在2型糖尿病视网膜病变患者血清中的水平及其临床意义[J]. 中华全科医学, 2020, 18(6): 959-961. doi: 10.16766/j.cnki.issn.1674-4152.001402 XUE L Z, TAN H T, ZHANG S Q, et al. The level of serum fibroblast growth factor 21 in patients with type 2 diabetic retinopathy and its clinical significance[J]. Chinese Journal of General Practice, 2020, 18(6): 959-961. doi: 10.16766/j.cnki.issn.1674-4152.001402
[5]	龙慧民, 项卓仪. 转移性尿路上皮癌的药物治疗研究进展[J]. 浙江医学, 2021, 43(17): 1824-1829, 1845. LONG H M, XIANG Z Y. Advances in drug therapy for metastatic urothelial carcinoma[J]. Zhejiang Medical Journal, 2021, 43(17): 1824-1829, 1845.
[6]	张晶镔, 王文萍. 血清25羟维生素D与气阴两虚2型糖尿病合并甲状腺结节TI-RADS分级相关性分析[J]. 辽宁中医药大学学报, 2024, 26(5): 163-166. ZHANG J B, WANG W P. Correlation analysis between serum 25-hydroxyvitamin D and TI-RADS grade of thyroid nodules in type 2 diabetes mellitus with deficiency of both qi and yin[J]. Journal of Liaoning University of Traditional Chinese Medicine, 2024, 26(5): 163-166.
[7]	胡文豪, 黄佳. miR-615-3p通过靶向HMGB3促进膀胱癌的转移[J]. 中国卫生检验杂志, 2021, 31(21): 2575-2580. HU W H, HUANG J. miR-615-3p promotes the metastasis of bladder cancer by targeting HMGB3[J]. Chinese Journal of Health Inspection, 2021, 31(21): 2575-2580.
[8]	BROOKS N A, KOKOROVIC A, XIAO L, et al. The obesity paradox: defining the impact of body mass index and diabetes mellitus for patients with non-muscle-invasive bladder cancer treated with bacillus calmette-cuerin[J]. BJU International, 2020, 128(1): 65-71.
[9]	沈丹. DKK1在膀胱癌组织中表达水平与预后的相关性[J]. 中国卫生检验杂志, 2022, 32(7): 839-841. SHEN D. The correlation between the expression level of Shendan DKK1 in bladder cancer tissues and prognosis[J]. Chinese Journal of Health Inspection, 2022, 32(7): 839-841.
[10]	HUA R, LI Q, GAO H, et al. Association of human telomerase reverse transcriptase promoter mutation with unfavorable prognosis in glioma: a systematic review and meta-analysis[J]. J Res Med Sci, 2023, 28: 47. DOI: 10.4103/jrms.jrms_371_22.
[11]	YANG R, HAN Y, GUAN X, et al. Regulation and clinical potential of telomerase reverse transcriptase (TERT/hTERT) in breast cancer[J]. Cell Commun Signal, 2023, 21(1): 218.
[12]	SUN S, WANG Y, LIU Y, et al. Telomerase reverse transcriptase gene polymorphisms and cervical cancer susceptibility in high-risk human papillomavirus-infected women[J]. J Obstet Gynaecol Res, 2024, 50(1): 95-102.
[13]	BATISTA R, LIMA L, VINAGRE J, et al. TERT promoter mutation as a potential predictive biomarker in BCG-Treated bladder cancer patients[J]. Int J Mol Sci, 2020, 21(3): 947.
[14]	曾平, 郭鹏翔, 骆横. 人端粒酶逆转录酶在肿瘤转录调控机制中的研究进展[J]. 实用肿瘤学杂志, 2023, 37(1): 68-72. ZENG P, GUO P X, LUO H. Research progress of human telomerase reverse transcriptase in tumor transcriptional regulation mechanism[J]. Journal of Applied Oncology, 2023, 37(1): 68-72.
[15]	DRATWA M, WYSOCZANSKA B, TURLEJ E, et al. Heterogeneity of telomerase reverse transcriptase mutation and expression, telomerase activity and telomere length across human cancer cell lines cultured in vitro[J]. Exp Cell Res, 2020, 396(1): 112298. DOI: 10.1016/j.yexcr.2020.112298.
[16]	HAYASHI Y, FUJITA K, MATSUZAKI K, et al. Clinical significance of hotspot mutation analysis of urinary cell-free DNA in urothelial bladder cancer[J]. Front Oncol, 2020, 10: 755. DOI: 10.3389/fonc.2020.00755.