山东大学耳鼻喉眼学报 ›› 2019, Vol. 33 ›› Issue (5): 96-100.doi: 10.6040/j.issn.1673-3770.0.2019.468

• 论著 • 上一篇    下一篇

42例喉癌患者血清 microRNAlet-7a 水平的变化及意义

罗露,周恩,欧阳思,陈义,肖旭平,王继华()   

  1. 湖南省人民医院耳鼻咽喉-头颈外科,湖南 长沙 410005
  • 收稿日期:2018-10-22 修回日期:2019-01-02 出版日期:2019-09-20 发布日期:2019-10-15
  • 通讯作者: 王继华 E-mail:wangjihua29003@163.com

Expression of the microRNA let-7a in the serum of 42 patients with laryngeal cancer and its significance

Lu LUO,En ZHOU,Si OUYANG,Yi CHEN,Xuping XIAO,Jihua WANG()   

  1. Department of Otolaryngology-Head and Neck Surgery, Hunan Provincial People′s Hospital, Changsha 41005, Hunan, China
  • Received:2018-10-22 Revised:2019-01-02 Online:2019-09-20 Published:2019-10-15
  • Contact: Jihua WANG E-mail:wangjihua29003@163.com

摘要: 目的

探讨42例喉癌患者血清microRNAlet-7a水平的变化及其对喉癌的诊断价值。

方法

qRT-PCR检测42例喉癌患者(手术前后)及42例健康体检者血清miRNA let-7a的表达,分析血清let-7a水平与喉癌的临床病理因素的关系,用受试者工作曲线(ROC)分析其对喉癌的诊断效能。

结果

血清let-7a在实验组比正常对照组相对表达下降分别为:0.38±0.0831、0.933±0.0723,差异有统计学意义;喉癌患者术前比术后1周血清let-7a的相对表达下降为:0.38±0.0831、0.488±0.1468,差异有统计学意义。血清let-7a的相对表达量与淋巴结转移有关联(P<0.05);与年龄、性别、饮酒、吸烟、浸润深度、肿瘤分型、TNM分期、分化程度无关联(P >0.05)。受试者工作曲线(ROC)显示以0.765为血清let-7a相对表达量的最佳临界值诊断喉癌,其灵敏度为76.5%,特异度为76.1%,AUC为0.850,95%置信区间为0.776~0.932。

结论

喉癌患者血清miRNAlet-7a水平较健康者出现下调,let-7a有望成为诊断喉癌的新的分子标志物。血清let-7a水平与淋巴结转移有关,有助于肿瘤病情判断与术后病情监测,但有待进一步研究。

关键词: 喉癌, microRNA, 血清

Abstract: Objective

To investigate changes in the serum let-7a expression in laryngeal squamous cell carcinoma (LSCC) patients and the diagnostic value of let-7a for LSCC.

Methods

Forty-two LSCC patients and 42 healthy subjects who were hospitalized in our hospital were enrolled in this study. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to determine the expression level of let-7a in patient serum samples, the association between serum let-7a levels and clinical and pathological LSCC parameters, and the diagnostic efficacy of let-7a for LSCC.

Results

Relative expression levels of let7a in the experimental (0.380±0.083) and normal control (0.933±0.0723) groups were significantly different . Relative let-7a expression levels in patients with laryngeal cancer before (0.380±0.0831) and after (0.488±0.1468) surgery were also significantly different. The let-7a level in tissues was associated with lymph node metastasis , but not with gender, age, smoking, alcohol consumption, tumor classification, infiltration depth, TNM stage, or degree of differentiation . ROC curve analysis showed that the best critical value for the relative expression of let-7a in 0.765 was laryngeal carcinoma with a sensitivity of 756.0%, a specificity of 76.1%, an AUC of 0.850, and a 95% confidence interval of 0.776-0.932.

Conclusion

Overall, we confirmed that serum let-7a expression is down-regulated in LSCC patients and is a potential molecular marker for laryngeal cancer diagnosis. Our findings also showed that the serum let-7a level is associated with lymph node metastasis, which is helpful for tumor disease judgment and postoperative tumor monitoring, but further research is needed to validate these findings.

Key words: Laryngeal carcinoma, microRNA, Serum

中图分类号: 

  • R767.1

图1

喉癌患者及正常人血清miRNAlet-7a的表达"

表1

喉癌病人血清miRNAlet-7a相对表达量与临床病理参数的关系 serum miRNAlet-7a and clinicopathological parameters in patients with laryngeal cancer"

临床病理参数 总例数 let-7a表达量 t P
性别 38 0.381±0.087 0.158 0.876
4 0.374±0.042

年龄

(岁)

≤60 24 0.371±0.079 0.846 0.403
>60 18 0.393±0.089
吸烟 吸烟 30 0.372±0.088 0.844 0.403
不吸烟 12 0.396±0.069
饮酒 饮酒 25 0.377±0.078 0.341 0.735
不饮酒 17 0.386±0.092
肿瘤分型 声门上型 9 0.371±0.052 0.413 0.682
声门型 33 0.384±0.090

淋巴结

转移

35 0.393±0.081 2.250 0.03
7 0.319±0.070
浸润深度 T1~T2 38 0.377±0.084 0.747 0.459
T3~T4 4 0.41±0.084
TNM分期 I~II 33 0.388±0.080 1.118 0.27
III~IV 9 0.353±0.093
分化程度 中分化 6 0.380±0.088 0.220 0.827
高分化 36 0.384±0.029

图2

血清miRNAlet-7a诊断喉癌的ROC曲线"

1 陈文杰, 王斌全, 高伟, 等 . 喉癌流行病学特征及影响因素分析[J]. 中国当代医药, 2015, 22(12): 43-46.
CHEN Wenjie , WANG Binquan , GAO Wei , et al . Analysis of epidemiologic features and influence factors of carcinoma of larynx[J]. China Modern Medicine, 2015, 22(12): 43-46.
2 Olaleye O , Siddiq S , Ekrikpo U , et al . Regional differences in incidence and mortality trends in cancers of the larynx, thyroid, oral cavity and pharynx in England and Scotland: 1975-2002[J]. OJEpi, 2013, 3(2): 70-78. doi: 10.4236/ojepi.2013.32011 .
doi: 10.4236/ojepi.2013.32011
3 李文明,魏东敏,钱晔,等 .支撑喉镜下CO_2激光治疗喉癌的疗效分析[J].山东大学耳鼻喉眼学报,2018,32(6):13-17.doi:10.6040/j.issn.1673-3770.1.2018.025 .
doi: 10.6040/j.issn.1673-3770.1.2018.025
LI Wenming , WEI Dongmin , QIAN Ye , et al . Evaluate the curative effect of CO2 laser in treatment of laryngeal carcinoma[J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2018, 32(6): 13-17. doi:10.6040/j.issn.1673-3770.1.2018.025 .
doi: 10.6040/j.issn.1673-3770.1.2018.025
4 Forastiere AA , Weber RS , Trotti A . Organ Preservation for Advanced Larynx Cancer: Issues and Outcomes[J]. Journal of Clinical Oncology, 2015, 33(29):3262-3268.doi:10.1200/jco.2015.61.2978 .
doi: 10.1200/jco.2015.61.2978
5 Chen CC , You JY , Lung J , et al . Aberrant let7a/HMGA2 signaling activity with unique clinical phenotype in JAK2 -mutated myeloproliferative neoplasms[J]. Haematologica, 2017, 102(3): 509-518. doi:10.3324/haematol.2016.154385 .
doi: 10.3324/haematol.2016.154385
6 Xu CW , Sun X , Qin SD , et al . Let-7a regulates mammosphere formation capacity through Ras/NF-κB and Ras/MAPK/ERK pathway in breast cancer stem cells[J]. Cell Cycle, 2015, 14(11): 1686-1697. doi:10.1080/15384101.2015.1030547 .
doi: 10.1080/15384101.2015.1030547
7 Chen CC , You JY , Gau JP , et al . Favorable clinical outcome and unique characteristics in association with Twist1 overexpression in de novo acute myeloid leukemia[J]. Blood Cancer J,2015,5:e339. doi: 10.1038/bcj. 2015.67 .
doi: 10.1038/bcj. 2015.67
8 Deng MM , Hou JW , Hu J , et al . Hepatitis B virus mRNAs functionally sequester let-7a and enhance hepatocellular carcinoma[J]. Cancer Lett, 2016, 383(1): 62-72. doi:10.1016/j.canlet.2016.09.028 .
doi: 10.1016/j.canlet.2016.09.028
9 马丽娟, 刘金华, 肖旭平 . 喉癌组织miRNAlet-7a和HMGA2表达临床意义研究[J]. 中华肿瘤防治杂志, 2016, 23(2): 74-78. doi:10.16073/j.cnki.cjcpt.2016.02. 006 .
doi: 10.16073/j.cnki.cjcpt.2016.02.006
MA Lijuan , LIU Jinhua , XIAO Xuping . Clinical significance of expressions of miRNA let-7a and HMGA2 in laryngeal squamous cell carcinoma tissues[J]. Chinese Journal of Cancer Prevention and Treatment, 2016, 23(2): 74-78. doi:10.16073/j.cnki.cjcpt.2016.02.006 .
doi: 10.16073/j.cnki.cjcpt.2016.02.006
10 尹娟 . Let-7a在喉癌细胞中调控HMGA2的机制研究[D]. 长沙: 湖南师范大学, 2017.
11 周恩 . let-7a调控HMGA2对喉癌Hep-2细胞裸鼠移植瘤生长的影响及其机制[D]. 长沙:湖南师范大学, 2017:34-77.
12 Petriella D , De Summa S , Lacalamita R , et al . miRNA profiling in serum and tissue samples to assess noninvasive biomarkers for NSCLC clinical outcome[J]. Tumour Biol, 2016, 37(4): 5503-5513. doi:10.1007/s13277-015-4391-1 .
doi: 10.1007/s13277-015-4391-1
13 Witwer KW . Circulating microRNA biomarker studies: pitfalls and potential solutions[J]. Clin Chem, 2015, 61(1): 56-63. doi:10.1373/clinchem.2014.221341 .
doi: 10.1373/clinchem.2014.221341
14 Chen WD , Li SJ . Circulating microRNA as a novel biomarker for pulmonary arterial hypertension due to congenital heart disease[J]. Pediatr Cardiol, 2017, 38(1): 86-94. doi:10.1007/s00246-016-1487-3 .
doi: 10.1007/s00246-016-1487-3
15 Hu ZB , Chen X , Zhao Y , et al . Serum microRNA signatures identified in a genome-wide serum microRNA expression profiling predict survival of non-small-cell lung cancer[J]. J Clin Oncol, 2010, 28(10): 1721-1726. doi:10.1200/JCO.2009.24.9342 .
doi: 10.1200/JCO.2009.24.9342
16 Huang YR , Yu S , Cao ST , et al . MicroRNA-222 promotes invasion and metastasis of papillary thyroid cancer through targeting protein phosphatase 2 regulatory subunit b alpha expression[J]. Thyroid, 2018, 28(9): 1162-1173. doi:10.1089/thy.2017.0665 .
doi: 10.1089/thy.2017.0665
17 Wang CL , Wang D , Yan BZ , et al . Long non-coding RNA NEAT1 promotes viability and migration of gastric cancer cell lines through up-regulation of microRNA-17[J]. Eur Rev Med Pharmacol Sci, 2018, 22(13): 4128-4137. doi:10.26355/eurrev_201807_15405 .
doi: 10.26355/eurrev_201807_15405
18 Li Y , Dai Y , Zhang XJ , et al . Three-layered polyplex as a microRNA targeted delivery system for breast cancer gene therapy[J]. Nanotechnology, 2017, 28(28): 285101. doi:10.1088/1361-6528/aa757f .
doi: 10.1088/1361-6528/aa757f
19 Hojo N , Hill A , Chirshev E , et al . Mechanism of tumor suppressor miRNA let-7 downregulation in ovarian cancer: transcription factor Snail represses let-7 and is associated with invasiveness phenotype[J]. Gynecologic Oncology, 2017, 147(1): 194. doi:10.1016/j.ygyno. 2017. 07.022 .
doi: 10.1016/j.ygyno. 2017. 07.022
20 Liu WJ , Xu Q , Sun LP , et al . Expression of serum let-7c, let-7i, and let-7f microRNA with its target gene, pepsinogen C, in gastric cancer and precancerous disease[J]. Tumour Biol, 2015, 36(5): 3337-3343. doi:10.1007/s13277-014-2967-9 .
doi: 10.1007/s13277-014-2967-9
[1] 肖俊华,潘庆春,晋舒. 基于全球疾病负担数据库分析职业硫酸暴露下喉癌患者的死亡趋势[J]. 山东大学耳鼻喉眼学报, 2026, 40(3): 55-61.
[2] 吉睿,刘雅洁,王佳琪,史雅文,张炜明,殷敏. 慢性间歇性缺氧对大鼠茎突舌肌的影响及作用机制[J]. 山东大学耳鼻喉眼学报, 2026, 40(2): 44-48.
[3] 章娜娜,黄冠江,卢标清. 联合中医证型分析喉癌变的影响因素及构建预测模型[J]. 山东大学耳鼻喉眼学报, 2026, 40(1): 29-37.
[4] 刘丹凤,潘庆春,李代波,封雪飞,任健. 1990—2021年中国归因于过量饮酒的喉癌疾病负担分析及未来趋势预测[J]. 山东大学耳鼻喉眼学报, 2025, 39(5): 61-69.
[5] 谢枫,许贞菊,吴策,刘杰,臧传善,张龙宵,韩敏. 喉神经内分泌肿瘤26例临床病理特征及生存分析[J]. 山东大学耳鼻喉眼学报, 2025, 39(2): 79-86.
[6] 周荷青,申琪. 中医药治疗变应性鼻炎疗效的生物标志物研究进展[J]. 山东大学耳鼻喉眼学报, 2025, 39(2): 168-176.
[7] 曲翔宇,朱晗,柳忠禄,牟亚魁,郭文涛,张华. 会厌舌瓣在喉癌声门上缺损修复术中的应用[J]. 山东大学耳鼻喉眼学报, 2025, 39(1): 77-84.
[8] 刘萍,顾子君,储婷,陈曦,程雷. 高流量呼吸湿化治疗仪在喉癌术后人工气道非机械通气患者中的应用效果研究[J]. 山东大学耳鼻喉眼学报, 2024, 38(5): 31-36.
[9] 王靖淞,余灿,张西,邓启成,谢卓良,赵锐,温蓓,刘海. KRT4在喉癌及癌旁正常黏膜组织中的表达及临床意义[J]. 山东大学耳鼻喉眼学报, 2024, 38(3): 12-17.
[10] 张竹萍,叶琪,郭蓓,林凌. 叶酸受体阳性循环肿瘤细胞检测在喉鳞状细胞癌诊断中的应用价值[J]. 山东大学耳鼻喉眼学报, 2023, 37(5): 50-53.
[11] 张西,邓启成,张震,程瑶,王靖淞,赵锐,刘海. 营养支持对喉癌术后咽瘘影响的Meta分析[J]. 山东大学耳鼻喉眼学报, 2023, 37(3): 51-59.
[12] 徐翀,王晓亭,易红良. 单细胞测序分析喉癌及其微环境代谢相关靶基因[J]. 山东大学耳鼻喉眼学报, 2023, 37(2): 33-38.
[13] 黄恒丰,马鲲鹏,杨迪,张丽君,张盛林. miR-181b-5P和EPB41L3蛋白在喉癌中的表达及临床意义[J]. 山东大学耳鼻喉眼学报, 2023, 37(1): 41-46.
[14] 李利杰,田秀芬. CO2激光联合低温等离子治疗早期声门型喉癌40例[J]. 山东大学耳鼻喉眼学报, 2022, 36(4): 79-85.
[15] 王媚 李志海. 喉癌干细胞:克服多药耐药性的潜在治疗靶点[J]. 山东大学耳鼻喉眼学报, 2022, 36(4): 120-128.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
No Suggested Reading articles found!