Different Morphological Structures of Breast Tumors Demonstrate Individual Drug Resistance Gene Expression Profiles

Abstract

Aim: To identify gene expression profiles involved in drug resistance of different morphological structures (tubular, alveolar, solid, trabecular, and discrete) presented in breast cancer. Material and Methods: Ten patients with luminal breast cancer have been included. A laser microdissection-assisted microarrays and qRT-PCR were used to perform whole-transcriptome profiling of different morphological structures, to select differentially expressed drug response genes, and to validate their expression. Results: We found 27 differentially expressed genes (p < 0.05) encoding drug uptake (SLC1A3, SLC23A2, etc.) and efflux (ABCC1, ABCG1, etc.) transporters, drug targets (TOP2A, TYMS, and Tubb3), and proteins that are involved in drug detoxification (NAT1 and ALDH1B1), cell cycle progression (CCND1, AKT1, etc.), apoptosis (CASP3, TXN2, etc.), and DNA repair (BRCA1 and USP11). Each type of structures showed an individual gene expression profile related to resistance and sensitivity to anticancer drugs. However, most of the genes (19/27; p < 0.05) were expressed in alveolar structures. Functional enrichment analysis showed that drug resistance is significantly associated with alveolar structures. Other structures demonstrated the similar number (10–13 out of 27) of expressed genes; however, the spectrum of resistance and sensitivity to different anticancer drugs varied. Conclusion: Different morphological structures of breast cancer show individual expression of drug resistance genes.

Morphophenotypic classification of tumor organoids as an indicator of drug exposure and penetration potential

“…We postulate here that ASA and RGYR may provide prospective metrics for assessing the potential of tumor organoids to be exposed and penetrated by the drug. Some recent studies have discussed the relationship between morphologies of in vivo and ex vivo tumors and their response to drugs [67, 68] showing that there is an interest in developing new measures to assess drug efficacy in tumors and tumor organoids based on their morphology. The organoids considered here (up to 150 μm in radius) are of the size that is below the diffusivity limits of oxygen or nutrients (200–250 μm).…”

Gene Expression of ABCG1, ABCG2, and ABCB1 and Their Role in Iranian Pediatric Patients with Acute Lymphoblastic Leukemia’s Recurrence

“…ABCG2 gene (located on chromosome 4q22.1) which encodes breast cancer resistance protein (BCRP) has an important role in resistance to mitoxantrone, methotrexate (MTX), cladribine, and topotecan (1). ABCG1 gene (located on chromosome 21q22.3) also known as ABC8 or WHITE1 (17) can make resistance to doxorubicin (18). Still published reports about multidrug resistance by ABCG1 in pediatric malignancies are rare.…”

Differential expression of NAT1 pharmacogene in hormone receptor positive vs. negative female breast tumors may affect drug treatment

“…Moreover, the cohort screened is accessible to other investigators and amenable to replication or expansion of this work. Other studies have examined NAT1 expression in breast cancer using qRT-PCR [22,[29][30][31][32][33][34][35][36][37], transcriptomics [19], proteomics, metabolomics or immunochemistry [23,[38][39][40][41]. Collectively, there is agreement that NAT1 is overexpressed in hormone receptor positive breast tumors, while more elaborate associations have also been proposed, namely, with relation to chemotherapy resistance [23] and better prognosis of tamoxifen treatment [22,34,39].…”