Gene expression profiles of breast cancer metastasis according to organ site
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ABSTRACT:
PROVIDER: PRJNA733195 | ENA |
REPOSITORIES: ENA
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Project description:In advanced breast cancer, biomarker identification and patient selection using a metastatic tumor biopsy is becoming more necessary. However, the biology of metastasis according to the organ site is largely unknown. Here, we evaluated the expression of 771 genes in 184 metastatic samples across 11 organs, including liver, lung, brain and bone, and made the following observations. First, all PAM50 molecular intrinsic subtypes were represented across organs and within immunohistochemistry-based groups. Second, HER2-low disease was identified across all organ sites, including bone, and HER2 expression significantly correlated with ERBB2 expression. Third, the majority of expression variation was explained by intrinsic subtype and not organ of metastasis. Fourth, subtypes and individual subtype-related genes/signatures were significantly associated with overall survival. Fifth, we identified 74 genes whose expression was organ-specific and subtype-independent. Finally, immune profiles were found more expressed in lung compared to brain or liver metastasis. Our results suggest that relevant tumor biology can be captured in metastatic tissues across a variety of organ sites; however, unique biological features according to organ site were also identified and future studies should explore their implications in diagnostic and therapeutic interventions.
2021-05-28 | GSE175692 | GEO
Project description:In advanced breast cancer, biomarker identification and patient selection using a metastatic tumor biopsy is becoming more necessary. However, the biology of metastasis according to the organ site is largely unknown. Here, we evaluated the expression of 771 genes in 184 metastatic samples across 11 organs, including liver, lung, brain, and bone, and made the following observations. First, all PAM50 molecular intrinsic subtypes were represented across organs and within immunohistochemistry-based groups. Second, HER2-low disease was identified across all organ sites, including bone, and HER2 expression significantly correlated with ERBB2 expression. Third, the majority of expression variation was explained by intrinsic subtype and not organ of metastasis. Fourth, subtypes and individual subtype-related genes/signatures were significantly associated with overall survival. Fifth, we identified 74 genes whose expression was organ-specific and subtype-independent. Finally, immune profiles were found more expressed in lung compared to brain or liver metastasis. Our results suggest that relevant tumor biology can be captured in metastatic tissues across a variety of organ sites; however, unique biological features according to organ site were also identified and future studies should explore their implications in diagnostic and therapeutic interventions.
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Project description:Organ-specific tropism and adaptation after metastasis of ER+ breast cancers
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Project description:Triple negative breast cancer has an extremely poor prognosis due to lack of available targeted treatments, especially for metastasis. Metastatic sites frequently include the lymph nodes and the lungs, and during the metastatic process, breast cancer cells must come into contact with the extracellular matrix (ECM) at every step. The ECM provides both structural support and biochemical cues, and cell-ECM interactions can lead to changes in to drug response. Here, we used fibroblast-derived ECM to perform high throughput drug screening of 4T1 breast cancer cells on metastatic organ ECM (lung) and we see that drug response differs to drug inhibition on plastic. The FDM that we are able to produce from different metastatic organs is abundant in, and contains a complex mixture of ECM proteins. We also show differences in ECM composition between the primary site and metastatic sites. Furthermore, we show that global kinase signalling of 4T1 cells on the ECM is relatively unchanged between organs, however we show large changes in signalling compared to plastic. Our study highlights the importance of context when testing drug response in vitro, showing that the consideration of the ECM is critically important.
2022-02-17 | PXD025786 | Pride
Project description:Patients diagnosed with estrogen receptor (ER) positive breast cancer have a prolonged risk of distal metastatic recurrence to vital organs. Metastatic disease is incurable at present due to the development of treatment resistant cell populations. Here we used single-cell RNA sequencing to evaluate the transcriptome heterogeneity of ER+ breast cancer patient-derived xenografts (PDX) tropic for three common breast cancer metastatic sites – bone, brain, and liver – compared to primary tumors grown in the mammary fat pad. Metastatic cell populations at each location were phenotypically distinct from primary tumor cells with unique transcriptional programs indicative of signaling programs driven by specific transcription factors. Cells that metastasized to brain and liver tissue adopted gene expression programs indicative of the target organ microenvironments. Discerning the organ-specific phenotypic adaptations of metastatic ER+ breast cancer cells may help tailor appropriate therapies for individual patients and to each metastatic site.
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