中国癌症杂志 ›› 2022, Vol. 32 ›› Issue (8): 727-735.doi: 10.19401/j.cnki.1007-3639.2022.08.008

• 论著 • 上一篇    下一篇

血浆长链非编码RNA H19对乳腺癌新辅助治疗效果的预测价值

陈安莉1()(), 沈浩元2()(), 阳仕雄3, 邓春燕4, 胡超华2, 刘汉忠5, 王舒1, 钱芳1   

  1. 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
  • 收稿日期:2022-03-04 修回日期:2022-06-20 出版日期:2022-08-30 发布日期:2022-09-19
  • 通信作者: 沈浩元 E-mail:864293812@qq.com;shhfxgy7679@sina.com
  • 作者简介:陈安莉(ORCID: 0000-0002-5979-6010),硕士研究生在读,E-mail: 864293812@qq.com
  • 基金资助:
    湖北省卫生健康委员会联合基金(WJ2019H246)

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

CHEN Anli1()(), SHEN Haoyuan2()(), YANG Shixiong3, DENG Chunyan4, HU Chaohua2, LIU Hanzhong5, WANG Shu1, QIAN Fang1   

  1. 1. Postgraduate Training Base of Xiaogan Central Hospital of Jinzhou Medical University, Xiaogan 432000, Hubei Province, China
    2. Department of Thyroid and Breast Surgery, Affiliated Hospital of Wuhan University of Science and Technology (Xiaogan Central Hospital), Xiaogan 432000, Hubei Province, China
    3. Department of Central Laboratory, Affiliated Hospital of Wuhan University of Science and Technology (Xiaogan Central Hospital), Xiaogan 432000, Hubei Province, China
    4. Department of Pediatrics, Affiliated Hospital of Wuhan University of Science and Technology (Xiaogan Central Hospital), Xiaogan 432000, Hubei Province, China
    5. Department of Pathology, Affiliated Hospital of Wuhan University of Science and Technology (Xiaogan Central Hospital), Xiaogan 432000, Hubei Province, China
  • Received:2022-03-04 Revised:2022-06-20 Published:2022-08-30 Online:2022-09-19
  • Contact: SHEN Haoyuan E-mail:864293812@qq.com;shhfxgy7679@sina.com

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—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(P<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(P<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(P<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)(P<0.05),但与激素受体阳性乳腺癌相比差异无统计学意义(P>0.05),而TNBC患者显著低于激素受体阳性型(P<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(P<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(P>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(P<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。

关键词: 乳腺癌, 新辅助治疗, 长链非编码RNA, lncRNA H19, 病理学完全缓解

Abstract:

Background and purpose: Long noncoding RNA (LncRNA) plays an important role in the development of distant metastasis and drug 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 (P<0.05). The expression of H19 in pCR group decreased significantly with the progress of NAT (P<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, 4 and 6 cycles of NAT and after surgery(P<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 (P<0.05), but there was no significant difference compared with hormone receptor-positive breast cancer patients (P>0.05), while H19 expression level in TNBC patients was significantly lower compared with patients with hormone receptor-positive type (P<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 (P<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 (P>0.05), and there were significant differences in tumor residual load and lncRNA H19 expression after NAT (P<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.

Key words: Breast cancer, Neoadjuvant therapy, Long non-coding RNA, LncRNA H19, Pathological complete response

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