Tumor elastography and its association with cell-free tumor DNA in the plasma of breast tumor patients: A pilot study

Hao，Yi1; Yang，Wei2; Zheng，Wenyi2,3; Chen，Xiaona3,4; Wang，Hui1,5; Zhao，Liang1,5; Xu，Jinfeng6,7; Guo，Xia4

2021-08-01

10.21037/qims-20-443

Quantitative Imaging in Medicine and Surgery   影响因子和分区

2223-4292

2223-4306

Background: Breast tumor stiffness, which can be objectively and noninvasively evaluated by ultrasound elastography (UE), has been useful for the differentiation of benign and malignant breast lesions and the prediction of clinical outcomes. Liquid biopsy analyses, including cell-free tumor DNA (ctDNA), exhibit great potential for personalized treatment. This study aimed to investigate the correlations between the UE and ctDNA for early breast cancer diagnosis. Methods: Breast tumor stiffness in 10 patients were assessed by shear wave elastography (SWE), and the ctDNA of eight collected plasma specimens with different tumor stiffness were analyzed by whole-genome sequencing (WGS). Subsequently, the distribution of carcinoma-associated fibroblasts (CAFs) was investigated by detecting the expression levels of alpha-smooth muscle actin (α-SMA) in tissues of breast lesions. We validated the function of discoidin domain receptor 2 (DDR2) in breast tumor CAFs by knockout of fibroblast activation protein (FAP) with different tumor stiffness during cancer progression in vitro and vivo. Results: The UE estimates of tumor stiffness positively correlated with CAF-rich (α-SMA+) tumors (P<0.05). Copy number profiles and percent genome alterations were remarkably different between benign and malignant breast lesions. Somatic genomic alterations or structural variants of DDR2, ANTXRL, TPSG1, and TPSB2 genes were identified in ctDNA of plasma from breast lesions with high SWE values and an increase in the CAF content obtained from clinical samples. Deletion of FAP in breast tumor CAFs by CRISPR/Cas9-mediated gene knockout and decreased tumor stiffness resulted in downregulated expression of DDR2 (P<0.05), which in turn led to decreasing the tumor stiffness and carcinogenesis process in vitro and in vivo. Conclusions: These results have established proof of principle that WGS analysis of ctDNA could complement current UE approaches to assess tumor stiffness changes for the early diagnosis and prognostic assessment of breast cancer.

Breast cancer Cell-free tumor DNA (ctDNA) Copy number variation (CNV) Discoidin domain receptor 2 (DDR2) Tumor stiffness

SCI

英语

其他

WOS:000659230900013

2-s2.0-85107443603

Scopus

1.Department of Ultrasound,South China Hospital of Shenzhen University,Shenzhen,China
2.Department of Ultrasound,Shenzhen Hospital,Southern Medical University,Shenzhen,China
3.The Third School of Clinical Medicine,Southern Medical University,Guangzhou,China
4.Shenzhen Key Laboratory of Viral Oncology,Center for Clinical Research and Innovation (CCRI),Shenzhen Hospital,Southern Medical University,Shenzhen,China
5.Department of Ultrasound,Affiliated Tumor Hospital,Xinjiang Medical University,Urumqi,China
6.Department of Ultrasound,The Second Clinical Medical College,Jinan University,Shenzhen,China
7.The First Affiliated Hospital,Southern University of Science and Technology,Shenzhen,China

Hao，Yi,Yang，Wei,Zheng，Wenyi,et al. Tumor elastography and its association with cell-free tumor DNA in the plasma of breast tumor patients: A pilot study[J]. Quantitative Imaging in Medicine and Surgery,2021,11(8):3510-3534.

Hao，Yi.,Yang，Wei.,Zheng，Wenyi.,Chen，Xiaona.,Wang，Hui.,...&Guo，Xia.(2021).Tumor elastography and its association with cell-free tumor DNA in the plasma of breast tumor patients: A pilot study.Quantitative Imaging in Medicine and Surgery,11(8),3510-3534.

Hao，Yi,et al."Tumor elastography and its association with cell-free tumor DNA in the plasma of breast tumor patients: A pilot study".Quantitative Imaging in Medicine and Surgery 11.8(2021):3510-3534.