Shear Wave Elastography: A Non-Invasive Approach for Assessing TGF-β1/MAPK Signaling Molecules and EMT in Breast Cancer

Sisi Huang, Bo Wang, Ying Jiang, Shiyu Li, Junkang Li, Zhili Wang Department of Ultrasound, the First Medical Center, Chinese PLA General Hospital, Beijing, 100853, People’s Republic of ChinaCorrespondence: Zhili Wang, Department of Ultrasound, the First Medical Center, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853, People’s Republic of China, Tel +86015727396682, Email [email protected]: This study investigated the relationship between Shear Wave Elastography (SWE), TGF-β 1/MAPK signaling molecules, and epithelial-to-mesenchymal transition (EMT) in breast lesions, exploring the feasibility of SWE in early EMT identification for breast cancer.Methods: 117 breast lesions in 107 patients from July to November 2023 were consecutively enrolled. SWE was performed preoperatively, and elastic parameters were documented. Immunohistochemistry (IHC) assessed the expression levels of TGF-β 1, p38 MAPK, p-p38 MAPK, ERK1/2, p-ERK1/2, ERK5, p-ERK5, JNK, p-JNK, E-cadherin, β-catenin, N-cadherin, and Vimentin. Correlations between SWE parameters and biomarkers were analysed, and their diagnostic efficacy for axillary lymph node metastasis (LNM) was evaluated.Results: Among 117 breast lesions, 53 were classified as benign and 64 as malignant (25 exhibiting axillary LNM). Optimal SWE thresholds for distinguishing benign from malignant lesions were Emax = 106.7 kPa, Emean = 62.9 kPa, Emin = 22.5 kPa, Eratio = 3.4, and Esd = 21.2 kPa. For LNM prediction, cut-offs were Emax = 170.1 kPa, Emean = 118.5 kPa, and Eratio = 10.5. TGF-β 1 and E-cadherin showed significant predictive value for LNM (AUCs: 0.774 and 0.704, respectively). E-cadherin negatively correlated with SWE parameters, while TGF-β 1 and MAPK molecules (p38 MAPK, p-p38 MAPK) showed positive correlations. Lesions with “stiff rim sign” had significantly lower E-cadherin expression but elevated levels of TGF-β 1 (P< 0.001). Additionally, Vimentin, p38 MAPK and p-p38 MAPK levels were higher in the occurrence of the “stiff rim sign” (P all < 0.05).Conclusion: TGF-β 1, p38 MAPK, and E-cadherin demonstrated strong diagnostic capabilities and correlated with SWE parameters. SWE offers a promising non-invasive approach for assessing prognosis by identifying EMT characteristics at an earlier stage in breast cancer.Keywords: breast lesions, shear wave elastography, SWE, epithelial-to-mesenchymal transition, EMT, TGF-β 1, MAPK signaling molecules, axillary LNM