Objective: This study aimed to investigate the underlying mechanisms of breast cancer metastasis patterns through a transcriptomic analysis of breast cancer with organ-specific metastasis. Methods: (1) Breast cancer cell lines capable of specific lung and bone metastasis were constructed using the PyMT-1 cell line. (2) The IVIS imaging system was employed to screen cell lines with robust specific metastatic capabilities. (3) Transcriptome sequencing was conducted on the resultant breast cancer cell lines exhibiting specific metastasis. (4) The transcriptome sequencing data were analyzed to identify pathways influencing specific metastasis in breast cancer. (5) Validation of pathway-related genes through PCR detection. (6) Clinical validation of differentially expressed genes in paraffin specimens. Results: (1) The IVIS system confirmed the specific metastatic abilities of PyMT-1, Py-L1, Py-L2, Py-B1 and Py-B2 tumors. PyMT-1, Py-L1 and Py-B1 were chosen for further experiments. (2) Following transcriptome sequencing, differentially expressed genes were identified and enrichment analysis was conducted. Pairwise comparisons among the three cell lines revealed 917 differentially expressed genes between PyMT-1 and Py-L1 (including 641 upregulated and 276 downregulated genes); 4131 differentially expressed genes between PyMT-1 and Py-B1 (including 2158 upregulated and 1973 downregulated genes). Conclusions: This study analyzed the genetic background related to breast cancer-specific lung and bone metastasis at the transcriptome level. Obtained the corresponding differential expression profiles and potential functional pathways involved. Demonstrated the promoting roles of CCN2 and ITGB6 in breast cancer lung metastasis, and the promoting roles of CD44 and THBS1 in breast cancer bone metastasis.
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