食道鳞状细胞癌转录组液体活检法预测新辅助治疗的耐药性

SCI

6 June 2022

A transcriptomic liquid biopsy assay for predicting resistance to neoadjuvant therapy in esophageal squamous cell carcinoma

 (ATS, IF:4.3)

• Keisuke Okuno, Masanori Tokunaga, Yusuke Kinugasa et al. A transcriptomic liquid biopsy assay for predicting resistance to neoadjuvant therapy in esophageal squamous cell carcinoma. [J] .Ann Thorac Surg, 2022, undefined.

Objective 目的

To establish a liquid-biopsy assay to predict response to neoadjuvant therapy (NAT) in esophageal squamous cell carcinoma (ESCC) patients. 

建立一种预测食管鳞癌(ESCC)患者对新辅助治疗(NAT)反应的液体活检方法。

Summary Background Data 背景资料

Pretreatment prediction of resistance to NAT is of great significance for the selection of treatment options in ESCC patients. In this study, we comprehensively translated tissue-based microRNA (miRNA) and messenger RNA (mRNA) expression biomarkers into a liquid biopsy assay. 

预处理预测耐NAT对ESCC患者治疗方案的选择具有重要意义。在这项研究中，我们将基于组织的microRNA (miRNA)和信使RNA (mRNA)表达生物标志物全面翻译到液体活检试验中。

Methods 方法

We analyzed 186 clinical ESCC samples, which included 128 formalin-fixed paraffin-embedded and a matched subset of 58 serum samples, from 2 independent institutions. We performed quantitative reverse-transcription polymerase chain reaction, and developed a resistance-prediction model using the logistic regression analyses. 

我们分析了186份来自2个独立机构的临床ESCC样本，其中包括128份福尔马林固定石蜡包埋样本和58份匹配的血清样本。我们进行了定量逆转录聚合酶链反应，并利用逻辑回归分析建立了一个抗性预测模型。

Results 结果

We first evaluated the potential of 4-miRNAs and 3-mRNAs panel, which robustly predicted resistance to NAT (area under the curve [AUC]: 0.85). Moreover, addition of tumor size to this panel increased predictive potential to establish a combination signature (AUC: 0.92). We successfully validated this signature performance in independent cohort, and our model was more accurate when the signature was combined with clinical predictors (AUC: 0.81) to establish a NAT resistance risk (NATRR) model. Finally, we successfully translated our NATRR model into a liquid biopsy assay (AUC: 0.78), and a multivariate regression analysis revealed this model as an independent predictor for response to NAT (odds ratio: 6.10; P < 0.01). 

我们首先评估了4-miRNAs和3- mrna的潜力，它们可以准确预测NAT的耐药性(曲线下面积[AUC]: 0.85)。此外，肿瘤大小的加入增加了建立联合标记的预测潜力(AUC: 0.92)。我们成功地在独立队列中验证了这一特征表现，当该特征与临床预测因子(AUC: 0.81)结合建立NAT耐药风险(NATRR)模型时，我们的模型更加准确。最后，我们成功地将我们的NATRR模型转化为液体活检(AUC: 0.78)，并通过多元回归分析显示，该模型可作为对NAT反应的独立预测因子(优势比:6.10;P < 0.01)。

Conclusions 结论

We successfully developed a liquid biopsy-based assay that allows robust prediction of response to NAT in ESCC patients, and our assay provides fundamentals of developing precision-medicine.

我们成功地开发了一种基于液体活检的检测方法，可以可靠地预测ESCC患者对NAT的反应，我们的检测方法为发展精准医学提供了基础。