CROSS-CELL-LINE PHARMACOGENOMIC MAPPING OF CONSERVED PACLITAXEL RESISTANCE SIGNATURES IN BREAST CANCER
DOI:
https://doi.org/10.65327/hsn.v12i2.2491Keywords:
Breast cancer, Paclitaxel resistance, Pharmacogenomics, Gene expression, Drug resistanceAbstract
Durable therapeutic results are difficult to achieve in breast cancer patients because of resistance to paclitaxel, which can develop via heterogeneous molecular mechanisms. This work created a publicly available pharmacogenomic dataset to map conserved resistance-associated gene-expression signatures in four breast cancer cell lines: BAS, HS578T, MCF7 and MDA. After removing duplications and consolidating genes at the level, 20,160 observations were analyzed. The candidates were defined as high-magnitude genes (P < 0.05 and |logFC| ≥ 1) and cross-cell-line conservation was assessed using overlap, directional concordance, and Spearman correlation. Overall, the number of observations with high magnitudes ranged from 4.14% (HS578T) to 33.17% (MDA). Average pairwise Jaccard similarity was low (1.71–8.59%) and expression correlations were from −0.098 to 0.204, showing high cell-line specificity. Of the 215 genes shared in common across all models 28 consistently expressed in the same direction. CPE, USP18, FAT4, DUSP1, and TAPBPL were consistently found to be downregulated, while LYPD3, SDC1, MYBL2 and HK2 were consistently found to be upregulated. These results suggest that the signature can be used to define a focused functional signature for validation and highlight the importance of the directionality of the signatures when defining conserved paclitaxel-resistance biomarkers.
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