Integration of multi-omics data shows downregulation of mismatch repair, purin, and tublin pathways in AR-negative triple-negative chemotherapy-resistant breast tumors

Tang, X.; Thompson, K. J.; Kalari, K. R.; Sinnwell, J. P.; Suman, V.; Vedell, P. T.; McLaughlin, S. A.; Northfelt, D. W.; Moreno Aspitia, A.; Gray, R. J.; Carter, J. M.; Weinshilboum, R.; Wang, L.; Boughey, J. C.; Goetz, M. P.

doi:10.1101/2022.05.16.492190

bioRxiv · 10.1101/2022.05.16.492190

Integration of multi-omics data shows downregulation of mismatch repair, purin, and tublin pathways in AR-negative triple-negative chemotherapy-resistant breast tumors

Tang, X.·Thompson, K. J.·Kalari, K. R.·Sinnwell, J. P.·Suman, V.·Vedell, P. T.·McLaughlin, S. A.·Northfelt, D. W.·Moreno Aspitia, A.·Gray, R. J.·Carter, J. M.·Weinshilboum, R.·Wang, L.·Boughey, J. C.·Goetz, M. P.

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Abstract

Triple negative breast cancer (TNBC) patients who fail to achieve a pathological complete response to neoadjuvant chemotherapy (NAC) will likely experience recurrence of the disease within 3-4 years. Prognostic assessment of early recurrence could facilitate clinical decisions and impact disease survival. This study investigated pre- and post-NAC multi-omics data from both an in-house and a public clinical study to identify biomarkers of NAC response. We observed significant transcriptional differences associated with response in the residual disease (post-NAC biopsies), which did not exist in the pre-NAC biopsies. We further refined the post-NAC transcriptional changes to a 17-gene signature and machine learning models were applied to evaluate the signatures diagnostic potential (area under the curve [≥] 0.8). Interestingly, the signature was enriched with down-regulated immune genes and several of these genes demonstrated prognostic potential in basal TNBC tumors. Our 17-gene signature provides additional insight into TNBC recurrence, which warrants further investigation.

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Tang, X., Thompson, K. J., Kalari, K. R., Sinnwell, J. P., Suman, V., Vedell, P. T., McLaughlin, S. A., Northfelt, D. W., Moreno Aspitia, A., Gray, R. J., Carter, J. M., Weinshilboum, R., Wang, L., Boughey, J. C., Goetz, M. P.. 2022-05-18. Integration of multi-omics data shows downregulation of mismatch repair, purin, and tublin pathways in AR-negative triple-negative chemotherapy-resistant breast tumors. https://doi.org/10.1101/2022.05.16.492190

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