一个肿瘤免疫微环境相关的综合特征可以预测食管鳞癌新辅助放化疗后的病理反应和预后：来自中国的多中心研究。

A tumor immune microenvironment-related integrated signature can predict the pathological response and prognosis of esophageal squamous cell carcinoma following neoadjuvant chemoradiotherapy: A multicenter study in China.

机构信息

Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China Department of Pharmacology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China Department of Pathology, National Cancer Center/ National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China Department of Pathology, Anyang Cancer Hospital, The Fourth Affiliated Hospital of Henan University of Science and Technology, Anyang, Henan, 455000, China Department of Otology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China Department of Radiotherapy, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, 450008, China Department of General Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, 450008, China.

出版信息

Int J Surg. 2022 Nov;107:106960. doi: 10.1016/j.ijsu.2022.106960. Epub 2022 Oct 17.

DOI:10.1016/j.ijsu.2022.106960

PMID:36257585

Abstract

BACKGROUND

Currently, there are insufficient indicators for the reliable assessment of treatment response following neoadjuvant chemoradiotherapy (nCRT) in patients with esophageal squamous cell carcinoma (ESCC). Considering the essential role of protein-coding and non-coding RNAs in gene regulation and cellular processes, we systematically explored the molecular features and clinical significance of mRNA and lncRNA in 249 pretreatment biopsies from four hospitals in three districts with a high incidence of ESCC patients in China.

METHODS

During the discovery phrase, 13 differentially expressed genes were identified and validated between samples with a complete pathological response (pCR) and those with an incomplete pathological response (<pCR). Subsequently, we constructed a predictive mRNA and lncRNA signature (SERPINE1, LINC00592, and PRKAG2-AS1) using Fisher's linear discriminant analysis (FLDA) with stepwise variant-selection, followed by validation of its predictive ability in both internal and external cohorts.

RESULTS

Our signature showed great value in predicting the response to nCRT among ESCC samples and acted as an independent predictive indicator, in addition to demonstrating great potential in estimating patient prognosis. Interestingly, we found that patients with a high signature score had lower PD-L1 and IDO1 expression levels but higher CD8 T cells infiltration, suggesting that PD-L1 and IDO1 are negatively correlated with a high signature score and further associated with pCR and a better prognosis.

CONCLUSION

The present study identified a promising three-gene-based predictive signature that has powerful clinical implications for the identification of pCR and a good prognosis among patients with ESCC. Further immune-related exploration may provide an opportunity for future therapeutic combination.

摘要

背景

目前，对于接受新辅助放化疗（nCRT）的食管鳞癌（ESCC）患者，缺乏可靠的治疗反应评估指标。考虑到蛋白质编码和非编码 RNA 在基因调控和细胞过程中的重要作用，我们系统地研究了来自中国三个高发区的四家医院的 249 例预处理活检样本中 mRNA 和 lncRNA 的分子特征及其临床意义。

方法

在发现阶段，我们鉴定并验证了完全病理缓解（pCR）与不完全病理缓解（<pCR）患者之间的 13 个差异表达基因。随后，我们使用 Fisher 的线性判别分析（FLDA），采用逐步变量选择构建了一个预测性的 mRNA 和 lncRNA 特征（SERPINE1、LINC00592 和 PRKAG2-AS1），并在内部和外部队列中验证了其预测能力。

结果

我们的特征在预测 ESCC 样本对 nCRT 的反应方面具有很高的价值，并且除了证明其作为独立预测指标的潜力外，还具有估计患者预后的巨大潜力。有趣的是，我们发现高特征评分的患者 PD-L1 和 IDO1 的表达水平较低，但 CD8 T 细胞浸润较高，这表明 PD-L1 和 IDO1 与高特征评分呈负相关，并与 pCR 和更好的预后进一步相关。