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一个与潜在基因表达模式相关的放射组学特征,可用于预测肝细胞癌的预后和治疗反应。

A radiomics signature associated with underlying gene expression pattern for the prediction of prognosis and treatment response in hepatocellular carcinoma.

机构信息

Department of Radiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.

Department of PET/CT, The First Affiliated Hospital of Harbin Medical University, Harbin, China.

出版信息

Eur J Radiol. 2023 Oct;167:111086. doi: 10.1016/j.ejrad.2023.111086. Epub 2023 Sep 6.

Abstract

PURPOSE

Identifying robust prognosis and treatment efficiency predictive biomarkers of hepatocellular carcinoma (HCC) is challenging. The purpose of this study is to develop a radiomics approach for predicting the overall survival (OS) based on pretreatment CT images and to explore the radiomic-associated key genes.

METHODS

Patients with pathologically or clinically proven HCC from three data sets were retrospectively included in this study. The institute internal data that received transarterial chemoembolization (TACE) treatment was used as the training set to construct the radiomics signature to predict OS by the least absolute shrinkage and selection operator COX (LASSO-COX) regression algorithms. The model was externally tested in 41 patients from The Cancer Genome Atlas (TCGA) with available CT images. Area under the receiver operating characteristics curve (AUC) and the log-rank test were used for survival analysis based on high versus low radiomics score. RNA sequencing data of TCGA and Gene Expression Omnibus (GEO) public database were used for gene expression analysis.

RESULTS

A total of 752 patients were divided into the Radiomics cohort (n = 267), the TCGA cohort (n = 338) and GEO cohort (n = 147). The rad-score divided patients into high and low risk groups, with significant survival differences (P < 0.0001 and P = 0.0055) in the training and external test set. The AUC for 5 years' OS were 0.730 and 0.695, respectively. Seven OS-related genes (SPP1, GJA5, GJA4, INMT, PDZD4, ALDOA and MAFG) were identified, all of which were related with TACE efficiency, except for MAFG (P greater than 0.05).

CONCLUSIONS

CT-radiomics signature could effectively predict the prognosis and treatment response of HCC, which were also associated with the tumor microenvironment heterogeneity.

摘要

目的

识别具有稳健预后和治疗效率预测能力的肝癌(HCC)生物标志物具有挑战性。本研究旨在开发一种基于治疗前 CT 图像预测总生存期(OS)的放射组学方法,并探索放射组学相关的关键基因。

方法

回顾性纳入了来自三个数据集的经病理或临床证实的 HCC 患者。本研究所接受经动脉化疗栓塞(TACE)治疗的内部数据被用作训练集,通过最小绝对收缩和选择算子 COX(LASSO-COX)回归算法构建放射组学特征以预测 OS。该模型在来自癌症基因组图谱(TCGA)并具有可用 CT 图像的 41 名患者中进行了外部测试。基于高与低放射组学评分的生存分析采用接受者操作特征曲线下面积(AUC)和对数秩检验。TCGA 和基因表达综合数据库(GEO)公共数据库的 RNA 测序数据用于基因表达分析。

结果

共纳入 752 名患者,分为放射组学队列(n=267)、TCGA 队列(n=338)和 GEO 队列(n=147)。rad-score 将患者分为高风险和低风险组,在训练集和外部测试集中均存在显著的生存差异(P<0.0001 和 P=0.0055)。5 年 OS 的 AUC 分别为 0.730 和 0.695。确定了 7 个与 OS 相关的基因(SPP1、GJA5、GJA4、INMT、PDZD4、ALDOA 和 MAFG),除了 MAFG(P>0.05)之外,所有这些基因均与 TACE 效率相关。

结论

CT 放射组学特征可有效预测 HCC 的预后和治疗反应,并且与肿瘤微环境异质性相关。

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