超声黏弹性成像预测GEP100/Arf6介导的乳腺癌转移及其转移机制

Breast cancer metastasis is the leading cause of cancer-related death in women. At present, there is no means to predict breast cancer metastasis and assess patient prognosis accurately. Numerous studies have shown that the biomolecular mechanism of breast cancer metastasis can lead to changes in biomechanical characteristics of breast cancer including both elasticity and viscosity. Our previous research work also showed that the diagnostic performance of shear wave elastography was optimized in the diagnosis of breast carcinoma through combining with BI-RADS by weight. However, as a complex with both elastic and viscous biomechanical characteristics, it is not reasonable to measure the elasticity of a breast tumor ignoring its viscosity. Therefore, we propose that using shear wave viscoelastic imaging (SWD) to detect the biomechanical characteristics of breast cancer macroscopically could make accurate and timely diagnosis of breast cancer metastasis for patients. To validate the hypothesis, we will construct nude models of breast cancer with different invasion and metastasis through GEP100/Arf6 pathway. SWD will be used to collect the parameters of biomechanical characteristics for different nude modes. To explore the molecular mechanism of SWD predicting the metastatic potential of breast cancer cells, the correlation will be performed between the parameters of biomechanical characteristics and breast cancer cytoskeleton, extracellular matrix and related molecules on cell membrane, which are associated with biomechanics. The proposal aims at providing an new method to predict the metastasis of breast cancers and to assess the prognosis of patients. It would also help to find a potential targeted therapy theoretical through revealing biomechanical mechanisms of metastasis breast cancer.

乳腺癌转移是乳腺癌患者死亡的主要原因。目前尚无手段能准确地预测乳腺癌转移并评估患者预后。大量研究表明乳腺癌转移的生物分子机制可导致乳腺癌包括弹性、黏性等生物力学特征改变。我们前期研究也发现按权重联合BI-RADS优化了剪切波弹性成像对乳腺癌的诊断。然而，乳腺作为同时具有弹性和黏性生物力学特征的综合体，仅测量乳腺肿瘤的弹性而忽略黏性并不合理。因此，我们提出利用剪切波黏弹性成像（SWD）从宏观层面检测乳腺癌组织的生物力学特征或许可以准确地预测乳腺癌细胞的转移。为验证上述假设，我们将通过GEP100/Arf6途径构建侵袭转移力不同的乳腺癌动物模型。利用SWD采集不同乳腺癌动物模型的生物力学特征参数，分析特征参数与乳腺癌生物力学相关的细胞骨架、细胞外基质及细胞膜上分子的相关性，探索SWD预测乳腺癌细胞转移潜力的生物力学机制，为乳腺癌转移预测、患者预后评估和潜在靶向治疗模式提供新的方法和理论依据。

目前在乳腺癌诊治方面，迫切需要一种检查手段能够准确预测乳腺癌细胞转移、及早评估患者预后，从而降低患者由于复发和转移造成的死亡。研究发现，GEP100/Arf6 途径介导的乳腺癌侵袭转移，其机制与肿瘤微环境中肌动蛋白细胞骨架的动态变化、细胞外基质成分改变、上皮细胞-间充质细胞转化等多种途径造成的生物力学特征的改变相关。乳腺癌的侵袭转移除了受到分子机制的调控，生物力学机制是另一个影响乳腺癌侵袭转移的重要机制。通过剪切波黏弹性成像从宏观层面反映肿瘤组织生物力学特征的改变，对该肿瘤的转移、复发进行预测，进而对其患者预后进行评估，为乳腺癌的诊治找到一种全新、有效的预测评估模式。