动态对比增强 MRI 和体素内不相干运动鉴别不同血管正常化基因表达的乳腺癌分子亚型。

Dynamic Contrast Enhanced MRI and Intravoxel Incoherent Motion to Identify Molecular Subtypes of Breast Cancer with Different Vascular Normalization Gene Expression.

机构信息

Department of Radiology, Koo Foundation Sun Yat-Sen Cancer Center, Taipei, Taiwan.

School of Medicine, National Yang-Ming Chiao-Tung University, Taipei, Taiwan.

出版信息

Korean J Radiol. 2021 Jul;22(7):1021-1033. doi: 10.3348/kjr.2020.0760. Epub 2021 May 20.

OBJECTIVE

To assess the expression of vascular normalization genes in different molecular subtypes of breast cancer and to determine whether molecular subtypes with a higher vascular normalization gene expression can be identified using dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) and intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI).

MATERIALS AND METHODS

This prospective study evaluated 306 female (mean age ± standard deviation, 50 ± 10 years), recruited between January 2014 and August 2017, who had breast cancer larger than 1 cm in diameter (308 tumors). DCE MRI followed by IVIM DWI studies using 11 different b-values (0 to 1200 s/mm²) were performed on a 1.5T MRI system. The Tofts model and segmented biexponential IVIM analysis were used. For each tumor, the molecular subtype (according to six [I-VI] subtypes and PAM50 subtypes), expression profile of genes for vascular normalization, pericytes, and normal vascular signatures were determined using freshly frozen tissue. Statistical associations between imaging parameters and molecular subtypes were examined using logistic regression or linear regression with a significance level of = 0.05.

RESULTS

Breast cancer subtypes III and VI and PAM50 subtypes luminal A and normal-like exhibited a higher expression of genes for vascular normalization, pericyte markers, and normal vessel function signature ( < 0.001 for all) compared to other subtypes. Subtypes III and VI and PAM50 subtypes luminal A and normal-like, versus the remaining subtypes, showed significant associations with K, k, v, and IAUGC90 on DEC MRI, with relatively smaller values in the former. The subtype grouping was significantly associated with D, with relatively less restricted diffusion in subtypes III and VI and PAM50 subtypes luminal A and normal-like.

CONCLUSION

DCE MRI and IVIM parameters may identify molecular subtypes of breast cancers with a different vascular normalization gene expression.

目的

评估血管正常化基因在不同乳腺癌分子亚型中的表达，并确定是否可以使用动态对比增强（DCE）磁共振成像（MRI）和体素内不相干运动（IVIM）扩散加权成像（DWI）来识别具有更高血管正常化基因表达的分子亚型。

材料和方法

本前瞻性研究共纳入 306 名女性（平均年龄 ± 标准差，50 ± 10 岁），于 2014 年 1 月至 2017 年 8 月间入组，这些患者均患有直径大于 1 厘米的乳腺癌（308 个肿瘤）。在 1.5T MRI 系统上进行 DCE MRI 后，进行了使用 11 个不同 b 值（0 至 1200 s/mm²）的 IVIM DWI 研究。使用 Tofts 模型和分段双指数 IVIM 分析。对于每个肿瘤，根据六种[I-VI]亚型和 PAM50 亚型，使用新鲜冷冻组织确定血管正常化、周细胞和正常血管特征的基因表达谱。使用逻辑回归或线性回归，在显著性水平为 = 0.05 的情况下，检验影像学参数与分子亚型之间的统计学关联。

结果

与其他亚型相比，III 型和 VI 型乳腺癌和 PAM50 亚型 luminal A 和正常型表现出更高的血管正常化基因、周细胞标志物和正常血管功能特征的表达（所有 P < 0.001）。与其余亚型相比，III 型和 VI 型乳腺癌和 PAM50 亚型 luminal A 和正常型与 DCE MRI 上的 K、k、v 和 IAUGC90 具有显著关联，前者的这些值相对较小。亚型分组与 D 具有显著相关性，III 型和 VI 型乳腺癌和 PAM50 亚型 luminal A 和正常型的扩散受限相对较少。