Predictive value of plasma long non-coding RNA H19 in neoadjuvant therapy for breast cancer

Anli CHEN; Haoyuan SHEN; Shixiong YANG; Chunyan DENG; Chaohua HU; Hanzhong LIU; Shu WANG; Fang QIAN

doi:10.19401/j.cnki.1007-3639.2022.08.008

您当前的位置：

首页 >

文章列表页 >

Predictive value of plasma long non-coding RNA H19 in neoadjuvant therapy for breast cancer

Article | 更新时间：2025-12-31

- Predictive value of plasma long non-coding RNA H19 in neoadjuvant therapy for breast cancer
- China Oncology Vol. 32, Issue 8, Pages: 727-735(2022)
- 作者机构：
  
  1. 锦州医科大学孝感市中心医院研究生培养基地,湖北孝感 432000
  2. 武汉科技大学附属孝感医院（孝感市中心医院）甲状腺乳腺外科,湖北孝感 432000
  3. 武汉科技大学附属孝感医院（孝感市中心医院）中心实验室,湖北孝感 432000
  4. 武汉科技大学附属孝感医院（孝感市中心医院）儿科,湖北孝感 432000
  5. 武汉科技大学附属孝感医院（孝感市中心医院）病理科,湖北孝感 432000
- 作者简介：
- 基金信息：
- DOI：10.19401/j.cnki.1007-3639.2022.08.008
  CLC： R737.9
- Received：04 March 2022，
  
  Revised：2022-06-20，
  
  Published：30 August 2022
- 稿件说明：
移动端阅览
Anli CHEN, Haoyuan SHEN, Shixiong YANG, et al. Predictive value of plasma long non-coding RNA H19 in neoadjuvant therapy for breast cancer[J]. China Oncology, 2022, 32(8): 727-735.
DOI：

Anli CHEN, Haoyuan SHEN, Shixiong YANG, et al. Predictive value of plasma long non-coding RNA H19 in neoadjuvant therapy for breast cancer[J]. China Oncology, 2022, 32(8): 727-735. DOI： 10.19401/j.cnki.1007-3639.2022.08.008.

摘要

背景与目的：

长链非编码RNA（long non-coding RNA

lncRNA）在肿瘤的发生、发展、远处转移及耐药过程中充当重要角色

且lncRNA H19在乳腺癌组织及血浆中均有较高的表达

但其表达水平在乳腺癌新辅助治疗中的动态变化以及与相关临床病理学特征的关系尚未见报道。本研究探讨lncRNA H19对乳腺癌新辅助治疗效果的预测价值。

方法：

前瞻性选取2019年6月

#x02014;2021年12月武汉科技大学附属孝感医院（孝感市中心医院）甲乳外科收治的45例行新辅助治疗的乳腺癌患者为研究对象。所有病例根据其病理学类型及一般情况选择相应的治疗方案及周期

均采用实时荧光定量聚合酶链反应（real-time fluorescence quantitative polymerase chain reaction

RTFQ-PCR）动态检测新辅助治疗前

新辅助治疗2、4、6个周期后及手术后外周血lncRNA H19的表达水平及变化情况

对比分析在新辅助治疗不同时间段以及不同分子分型乳腺癌lncRNA H19表达量的差异及动态变化

并于手术后根据病理学特征评估新辅助治疗的效果。

结果：

所有研究对象均可在外周血血浆中检测到lncRNA H19的表达。入组的45例乳腺癌患者在新辅助治疗后有20例（44.4%）患者达到病理学完全缓解（pathological-complete-response

pCR）

25例（55.6%）患者未达到病理学完全缓解（non-pathological-complete-response

non-pCR）

且达到pCR的患者新辅助治疗前H19水平显著高于non-pCR患者（

0.05）;pCR组的H19表达随着新辅助治疗的进行均有明显下降的趋势（

0.05）

而 non-pCR组的H19表达水平在新辅助治疗后无明显下降趋势;在新辅助治疗动态变化中

lncRNA H19的表达量在新辅助治疗2、4和6个周期后及手术后较基线均有明显下降（

0.05）;人表皮生长因子受体2（human epidermal growth factor receptor 2

HER2）阳性乳腺癌患者新辅助治疗前血浆H19表达量显著高于三阴性乳腺癌（triple negative breast cancer

TNBC）（

0.05）

但与激素受体阳性乳腺癌相比差异无统计学意义（

0.05）

而TNBC患者显著低于激素受体阳性型（

0.05）;在新辅助治疗动态变化中

lncRNA H19的表达量在新辅助治疗2、4和6个周期后及手术后均明显下降（

0.05）;乳腺肿瘤大小、淋巴结状态及TNM分期与lncRNA H19表达量差异无统计学意义（

0.05）

而新辅助治疗后肿瘤残余负荷与lncRNA H19表达量差异有统计学意义（

0.05）;受试者工作特征（receiver operating characteristic

ROC）曲线分析结果显示

H19的曲线下面积（area under curve

AUC）为 0.70

灵敏度为100%

特异度为50%。

结论：

HER2

乳腺癌患者血浆H19表达量显著高于其他亚型

血浆中的lncRNA H19表达量在新辅助治疗后均有显著下降

且下降更明显的患者更容易达到pCR

因此血浆H19可作为预测不同分子亚型新辅助治疗效果的潜在预测因子。

Abstract

Background and purpose:

Long noncoding RNA (LncRNA) plays an important role in the development of distant metastasis and dr

ug resistance of tumors

and it is highly expressed in breast cancer tissues and plasma of breast cancer patients. However

the dynamic changes of its expression level in neoadjuvant therapy (NAT) for breast cancer and its relationship with relevant clinicopathological features have not been reported. This study aimed to investigate the predictive value of dynamic changes of plasma long lncRNA H19 in NAT for different molecular types of breast cancer.

Methods:

Forty-five breast cancer patients undergoing NAT were prospectively selected from January 2021 to December 2021 in the Department of Gynecology

Xiaogan Central Hospital

Wuhan University of Science and Technology. The corresponding treatment plan and cycle were selected for all cases according to their pathological types and general conditions. Real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR) was used to dynamically detect the expression levels and changes of lncRNA H19 in peripheral blood before NAT

after treatment with NAT for 2

4 and 6 cycles

and after surgery. The differences and dynamic changes of lncRNA H19 expression levels in different periods of NAT and different molecular types of breast cancer were compared and analyzed

and the efficacy of NAT was evaluated according to pathological features after surgery.

Results:

LncRNA H19 expression was detected in peripheral blood plasma of 45 breast cancer patients treated with NAT. Among them

20 patients (44.4%) achieved pathological complete response (pCR)

25 patients (55.6%) did not achieve pCR

and the level of H19 before NAT in patients who achieved pCR was significantly higher compared with non-pCR patients (

0.05). The expression of H19 in pCR group decreased significantly with the progress of NAT (

0.05)

while H19 expression level in non-pCR group showed no significant downward trend after NAT. In the dynamic changes of NAT

the expression of lncRNA H19 decreased significantly from baseline after 2

and 6 cycles of NAT and after surgery(

0.05); plasma H19 expression level in human epidermal growth factor receptor 2 (HER2) positive breast cancer patients was significantly higher compared with triple-negative breast cancer (TNBC) patients (

0.05)

but there was no significant difference compared with hormone receptor-positive breast cancer patients (

0.05)

while H19 expression level in TNBC patients was significantly lower compared with patients with hormone receptor-positive type (

0.05). In the dynamic changes of NAT

the expression level of lncRNA H19 decreased significantly after 2

4 and 6 cycles of NAT and after surgery (

0.05). There was no significant difference in tumor size

lymph node status

TNM stage and lncRNA H19 expression between patients with different types of breast cancer (

0.05)

and there were significant differences in tumor residual load and lncRNA H19 expression after NAT (

0.05). Receiver operating characteristic (ROC) curve analysis showed that the area under curve (AUC) of H19 was 0.70

the sensitivity was 100%

and the specificity was 50%.

Conclusions:

Plasma H19 expression level in patients with HER2 positive breast cancer is significantly higher compared with other subtypes. Plasma lncRNA H19 expression level is significantly decreased after NAT

and patients with more obvious decline are more likely to achieve pCR. Therefore

plasma H19 can be used as a potential predictor of NAT efficacy for different molecular subtypes.

关键词

Keywords

references

SUNG H , FERLAY J , SIEGEL R L , et al . Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries [J ] . CA Cancer J Clin , 2021 , 71 ( 3 ): 209 - 249 . DOI: 10.3322/caac.21660 http://doi.org/10.3322/caac.21660 https://onlinelibrary.wiley.com/doi/10.3322/caac.21660 https://onlinelibrary.wiley.com/doi/10.3322/caac.21660

中国抗癌协会乳腺癌专业委员会 . 中国抗癌协会乳腺癌诊治指南与规范(2021年版) [J ] . 中国癌症杂志 , 2021 , 31 ( 10 ): 954 - 1040 .

The Society of Breast Cancer China Anti-Cancer Association . Guidelines for breast cancer diagnosis and treatment by China Anti-Cancer Association (2021 edition) [J ] . China Oncol , 2021 , 31 ( 10 ): 954 - 1040 .

CAUDLE A S , GONZALEZ-ANGULO A M , HUNT K K , et al . Predictors of tumor progression during neoadjuvant chemotherapy in breast cancer [J ] . J Clin Oncol , 2010 , 28 ( 11 ): 1821 - 1828 . DOI: 10.1200/JCO.2009.25.3286 http://doi.org/10.1200/JCO.2009.25.3286 https://ascopubs.org/doi/10.1200/JCO.2009.25.3286 https://ascopubs.org/doi/10.1200/JCO.2009.25.3286

LIU S W , LI J C , KANG L , et al . Degradation of long non-coding RNA-CIR decelerates proliferation, invasion and migration, but promotes apoptosis of osteosarcoma cells [J ] . Cancer Cell Int , 2019 , 19 : 349 . DOI: 10.1186/s12935-019-1076-7 http://doi.org/10.1186/s12935-019-1076-7 https://doi.org/10.1186/s12935-019-1076-7 https://doi.org/10.1186/s12935-019-1076-7

ZHU Y , YANG Z , LUO X H , et al . Long noncoding RNA TTN-AS1 promotes the proliferation and migration of prostate cancer by inhibiting miR-1271 level [J ] . Eur Rev Med Pharmacol Sci , 2021 , 25 ( 3 ): 1165 .

SHA M , LIN M , WANG J , et al . Long non-coding RNA MIAT promotes gastric cancer growth and metastasis through regulation of miR-141/DDX5 pathway [J ] . J Exp Clin Cancer Res , 2018 , 37 ( 1 ): 58 . DOI: 10.1186/s13046-018-0725-3 http://doi.org/10.1186/s13046-018-0725-3 https://doi.org/10.1186/s13046-018-0725-3 https://doi.org/10.1186/s13046-018-0725-3

LIU Y H , HE A B , LIU B E , et al . Potential role of lncRNA H19 as a cancer biomarker in human cancers detection and diagnosis: a pooled analysis based on 1 585 subjects [J ] . Biomed Res Int , 2019 , 2019 : 9056458 .

ÖZGÜR E , FERHATOĞLU F , ŞEN F , et al . Circulating lncRNA H19 may be a useful marker of response to neoadjuvant chemotherapy in breast cancer [J ] . Cancer Biomark , 2020 , 27 ( 1 ): 11 - 17 . DOI: 10.3233/CBM-190085 http://doi.org/10.3233/CBM-190085 https://www.medra.org/servlet/aliasResolver?alias=iospress&doi=10.3233/CBM-190085 https://www.medra.org/servlet/aliasResolver?alias=iospress&doi=10.3233/CBM-190085

ZHANG K J , LUO Z L , ZHANG Y , et al . Circulating lncRNA H19 in plasma as a novel biomarker for breast cancer [J ] . Cancer Biomark , 2016 , 17 ( 2 ): 187 - 194 . DOI: 10.3233/CBM-160630 http://doi.org/10.3233/CBM-160630 https://www.medra.org/servlet/aliasResolver?alias=iospress&doi=10.3233/CBM-160630 https://www.medra.org/servlet/aliasResolver?alias=iospress&doi=10.3233/CBM-160630

ZHANG Y F , YAN J , LI C , et al . LncRNA H19 induced by helicobacter pylori infection promotes gastric cancer cell growth via enhancing NF-κB-induced inflammation [J ] . J Inflamm (Lond) , 2019 , 16 : 23 . DOI: 10.1186/s12950-019-0226-y http://doi.org/10.1186/s12950-019-0226-y https://doi.org/10.1186/s12950-019-0226-y https://doi.org/10.1186/s12950-019-0226-y

JERUSS J S , MITTENDORF E A , TUCKER S L , et al . Combined use of clinical and pathologic staging variables to define outcomes for breast cancer patients treated with neoadjuvant therapy [J ] . J Clin Oncol , 2008 , 26 ( 2 ): 246 - 252 . DOI: 10.1200/JCO.2007.11.5352 http://doi.org/10.1200/JCO.2007.11.5352 https://ascopubs.org/doi/10.1200/JCO.2007.11.5352 https://ascopubs.org/doi/10.1200/JCO.2007.11.5352

ROY R , PATTNAIK S , SIVAGURUNATHAN S , et al . Small ncRNA binding protein, PIWI: a potential molecular bridge between blood brain barrier and neuropathological conditions [J ] . Med Hypotheses , 2020 , 138 : 109609 . DOI: 10.1016/j.mehy.2020.109609 http://doi.org/10.1016/j.mehy.2020.109609 https://linkinghub.elsevier.com/retrieve/pii/S0306987719314239 https://linkinghub.elsevier.com/retrieve/pii/S0306987719314239

BRANNAN C I , DEES E C , INGRAM R S , et al . The product of the H19 gene may function as an RNA [J ] . Mol Cell Biol , 1990 , 10 ( 1 ): 28 - 36 .

SHEN X K , XIE B J , MA Z S , et al . Identification of novel long non-coding RNAs in triple-negative breast cancer [J ] . Oncotarget , 2015 , 6 ( 25 ): 21730 - 21739 . DOI: 10.18632/oncotarget.4419 http://doi.org/10.18632/oncotarget.4419 https://www.oncotarget.com/lookup/doi/10.18632/oncotarget.4419 https://www.oncotarget.com/lookup/doi/10.18632/oncotarget.4419

ZHOU S Y , HE Y J , YANG S J , et al . The regulatory roles of lncRNAs in the process of breast cancer invasion and metastasis [J ] . Biosci Rep , 2018 , 38 ( 5 ): BSR20180772.

WANG J , SUN J Y , YANG F . The role of long non-coding RNA H19 in breast cancer [J ] . Oncol Lett , 2020 , 19 ( 1 ): 7 - 16 .

Views

1194

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Advances in the diagnosis of pathological response by a second biopsy in breast cancer neoadjuvant therapy and their clinical significance

A study of neutrophil to lymphocyte ratio for the prediction of axillary pathological complete response after neoadjuvant therapy in breast cancer

Axillary management after neoadjuvant therapy for breast cancer and optimization of sentinel lymph node diagnosis and treatment

Research progress and prospects of MRI in predicting lymph node status in breast cancer

Progress and future prospects in local and systemic treatment of early breast cancer

Related Author

Bingqi XU

Guoqiang ZHANG

毕　钊

宋现让

陈　鹏

谢　丽

蒋　伟

宋兴国

Related Institution

Harbin Medical University Cancer Hospital, Department of Breast Oncoplastic Surgery

山东第一医科大学（山东省医学科学院）医学与生命科学学院

山东省肿瘤防治研究院（山东省肿瘤医院）乳腺外科一病区

山东省肿瘤防治研究院（山东省肿瘤医院）检验科

山东省莒县人民医院产科二病区

AI问答

⁰