AUTHOR=Xuan Zhidong , Ma Ting , Qin Yue , Guo Yajie TITLE=Role of Ultrasound Imaging in the Prediction of TRIM67 in Brain Metastases From Breast Cancer JOURNAL=Frontiers in Neurology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2022.889106 DOI=10.3389/fneur.2022.889106 ISSN=1664-2295 ABSTRACT=Objectives

Ultrasound (US) imaging is a relatively novel strategy to monitor the activity of the blood–brain barrier, which can facilitate the diagnosis and treatment of neurovascular-related metastatic tumors. The purpose of this study was to investigate the clinical significance of applying a combination of US imaging outcomes and the associated genes. This was performed to construct line drawings to facilitate the prediction of brain metastases arising from breast cancer.

Methods

The RNA transcript data from The Cancer Genome Atlas (TCGA) database was obtained for breast cancer, and the differentially expressed genes (DEGs) associated with tumor and brain tumor metastases were identified. Subsequently, key genes associated with survival prognosis were subsequently identified from the DEGs.

Results

Tripartite motif-containing protein 67 (TRIM67) was identified and the differential; in addition, the survival analyses of the TCGA database revealed that it was associated with brain tumor metastases and overall survival prognosis. Applying independent clinical cohort data, US-related features (microcalcification and lymph node metastasis) were associated with breast cancer tumor metastasis. Furthermore, ultrasonographic findings of microcalcifications showed correlations with TRIM67 expression. The study results revealed that six variables [stage, TRIM67, tumor size, regional lymph node staging (N), age, and HER2 status] were suitable predictors of tumor metastasis by applying support vector machine–recursive feature elimination. Among these, US-predicted tumor size correlated with tumor size classification, whereas US-predicted lymph node metastasis correlated with tumor N classification. The TRIM67 upregulation was accompanied by upregulation of the integrated breast cancer pathway; however, it leads to the downregulation of the miRNA targets in ECM and membrane receptors and the miRNAs involved in DNA damage response pathways.

Conclusions

The TRIM67 is a risk factor associated with brain metastases from breast cancer and it is considered a prognostic survival factor. The nomogram constructed from six variables—stage, TRIM67, tumor size, N, age, HER2 status—is an appropriate predictor to estimate the occurrence of breast cancer metastasis.