Patients with Triple-Negative Breast Cancer (TNBC), a highly heterogeneous and invasive subtype of breast cancer, do not benefit from hormonal therapy or trastuzumab; therefore, chemotherapy is considered the only option. We explored the effect of the chemotherapeutic drug cyclophosphamide (Cytoxan; Cy) on TNBC by an integrated bioinformatics approach.
Methods: Pharm Mapper, Gene Cards, and Swiss Target Prediction were used to identify potential targets of Cy. Differentially expressed genes (DEGs) in TNBC were screened out from four GEO datasets. Common genes were further evaluated by a protein-protein interaction network analysis, core gene identification, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, docking assays, and survival and immune cell infiltration analyses.
Results: We collected information on 1638 drug targets and 494 DEGs in TNBC, including 267 up-regulated and 227 down-regulated genes. In total, 68 overlapping genes were identified as common targets. Ten core genes were identified in network analysis; GO and KEGG analyses revealed enrichment for DNA damage and many signaling pathways. Four core gene targets were verified by molecular docking. Kaplan–Meier analysis revealed that two core genes were significantly related to an adverse overall survival; furthermore, immune infiltration analysis suggested that Cy affects the microenvironment.
Conclusions: Our integrative bioinformatics approach revealed that the anti-TNBC effect of Cy was mediated by DNA damage-related genes and many pathways. These findings provide a basis for further functional studies aimed at improving outcomes in TNBC.
Keywords:
Published on: Dec 24, 2021 Pages: 6-15
Full Text PDF
Full Text HTML
DOI: 10.17352/ijpsdr.000035
CrossMark
Publons
Harvard Library HOLLIS
Search IT
Semantic Scholar
Get Citation
Base Search
Scilit
OAI-PMH
ResearchGate
Academic Microsoft
GrowKudos
Universite de Paris
UW Libraries
SJSU King Library
SJSU King Library
NUS Library
McGill
DET KGL BIBLiOTEK
JCU Discovery
Universidad De Lima
WorldCat
VU on WorldCat
PTZ: We're glad you're here. Please click "create a new query" if you are a new visitor to our website and need further information from us.
If you are already a member of our network and need to keep track of any developments regarding a question you have already submitted, click "take me to my Query."