Identification and characterization of biomarkers and their functions for Lapatinib-resistant breast cancer

Abstract

Lapatinib, a novel oral dual tyrosine kinase inhibitor blocking HER1 and HER2 pathways, has presented beneficial effects on breast cancer with positive HER2. However, its efficacy is largely limited by the occurrence of acquired drug resistance. In this study, we aimed to explore the underlying molecular mechanisms of Lapatinib resistance using bioinformatics strategies. The gene expression profile of SKBR3-R (acquired Lapatinib-resistant) and SKBR3 (Lapatinib-sensitive) cell line was downloaded from gene expression omnibus database. Then, the differentially expressed genes (DEGs) were selected using dChip software. Furthermore, gene ontology (GO) and pathway enrichment analyses were carried out by using DAVID database. Finally, the protein-protein interaction network was constructed, and the hub genes in the network were analyzed by using STRING database. A total of 300 DEGs, such as HSPA5, MAP1LC3A and RASSF2, were screened out. GO functional enrichment analysis showed that the genes were associated with cell membrane component-related, stimulus-related and binding-related items. KEGG pathway analysis indicated that three dysfunctional pathways, including PPAR signaling pathway, cytokine-cytokine receptor interaction and pathways in cancer, were enriched. Protein-protein interaction network construction revealed that some hub genes, such as PPARG, TGFBI, TGFBR2, TIMP1, CTGF, UBA52 and JUN, might have an association with Lapatinib resistance. The present study offered new insights into the molecular mechanisms of Lapatinib resistance and identified a series of important hub genes that have the potential to be the targets for treatment of Lapatinib-resistant breast cancer.

Endogenous interaction profiling identifies DDX5 as an oncogenic coactivator of transcription factor Fra-1

“…However, a microarray-based gene expression analysis identified high expression of TGFBI involved in topotecan-resistant ovarian cancer [252]. Moreover, it has been reported that TGFBI might be associated with Lapatinib resistance in HER2-positive breast cancer cell lines [253]. On the other hand, epigenetic silencing of TGFBI by DNA methylation has been found to contribute to the trastuzumab resistance in HER2-positive cell models [254].…”

Indentification of Novel Biomarkers for Paroxysmal Non- Kinesigenic Dyskinesia Diagnosis Via Cerebrospinal Fluid and Plasma Proteomic Analysis

“…The GO is a structured and controlled vocabulary of terms, and widely recognized as the premier tool for the organization and functional annotation of molecular characteristics [18,20,21]. By interpreting the GO of differentially expressed proteins and then analyzing them statistically, we have obtained 42 significant CSF proteins and 57 significant plasma proteins.…”

Whole Blood mRNA Expression Pattern Differentiates AD Patients and Healthy Controls Through Bioinformatics Analysis

“…The screening criteria were adjusted P < 0.001 (Z. Lin & Lin, 2017;L. Zhang et al, 2017) and |fold change | ≥ 1.5.…”