Identification of key pathways and genes in response to trastuzumab treatment in breast cancer using bioinformatics analysis

Zeng, Fanxin; Fu, Jiangping; Hu, Fang; Tang, YH; Fang, Xiangdong; Zeng, Fanwei; Chu, Yanpeng

doi:10.18632/oncotarget.24605

Cited by 9 publications

(8 citation statements)

References 63 publications

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“…Recently, bioinformatics methods were widely used in cancer research and applied to study the molecular mechanisms of diseases [ 23 – 28 ]. The pathogenesis of TNBC may be a series of modifications of genetic, genomic and expression profiles [ 29 ].…”

Section: Introductionmentioning

confidence: 99%

Highly heterogeneous-related genes of triple-negative breast cancer: potential diagnostic and prognostic biomarkers

Liu

Teng

et al. 2021

BMC Cancer

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Background Triple-negative breast cancer (TNBC) is a highly heterogeneous subtype of breast cancer, showing aggressive clinical behaviors and poor outcomes. It urgently needs new therapeutic strategies to improve the prognosis of TNBC. Bioinformatics analyses have been widely used to identify potential biomarkers for facilitating TNBC diagnosis and management. Methods We identified potential biomarkers and analyzed their diagnostic and prognostic values using bioinformatics approaches. Including differential expression gene (DEG) analysis, Receiver Operating Characteristic (ROC) curve analysis, functional enrichment analysis, Protein-Protein Interaction (PPI) network construction, survival analysis, multivariate Cox regression analysis, and Non-negative Matrix Factorization (NMF). Results A total of 105 DEGs were identified between TNBC and other breast cancer subtypes, which were regarded as heterogeneous-related genes. Subsequently, the KEGG enrichment analysis showed that these genes were significantly enriched in ‘cell cycle’ and ‘oocyte meiosis’ related pathways. Four (FAM83B, KITLG, CFD and RBM24) of 105 genes were identified as prognostic signatures in the disease-free interval (DFI) of TNBC patients, as for progression-free interval (PFI), five genes (FAM83B, EXO1, S100B, TYMS and CFD) were obtained. Time-dependent ROC analysis indicated that the multivariate Cox regression models, which were constructed based on these genes, had great predictive performances. Finally, the survival analysis of TNBC subtypes (mesenchymal stem-like [MSL] and mesenchymal [MES]) suggested that FAM83B significantly affected the prognosis of patients. Conclusions The multivariate Cox regression models constructed from four heterogeneous-related genes (FAM83B, KITLG, RBM24 and S100B) showed great prediction performance for TNBC patients’ prognostic. Moreover, FAM83B was an important prognostic feature in several TNBC subtypes (MSL and MES). Our findings provided new biomarkers to facilitate the targeted therapies of TNBC and TNBC subtypes.

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Section: Introductionmentioning

confidence: 99%

Highly heterogeneous-related genes of triple-negative breast cancer: potential diagnostic and prognostic biomarkers

Liu

Teng

et al. 2021

BMC Cancer

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“…The spliceosome pathway was included among the increased activated pathways in the post-treatment HER2-positive group. Spliceosomes play a role in the alternative mRNA splicing machinery, which is induced by platinum and trastuzumab-based treatment 38 , 39 . In addition, the nucleotide excision repair pathway was also activated.…”

Section: Resultsmentioning

confidence: 99%

Temporal dynamics from phosphoproteomics using endoscopic biopsy specimens provides new therapeutic targets in stage IV gastric cancer

Hirano

Abe

Nojima

et al. 2022

Sci Rep

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Phosphoproteomic analysis expands our understanding of cancer biology. However, the feasibility of phosphoproteomic analysis using endoscopically collected tumor samples, especially with regards to dynamic changes upon drug treatment, remains unknown in stage IV gastric cancer. Here, we conducted a phosphoproteomic analysis using paired endoscopic biopsy specimens of pre- and post-treatment tumors (Ts) and non-tumor adjacent tissues (NATs) obtained from 4 HER2-positive gastric cancer patients who received trastuzumab-based treatment and from pre-treatment Ts and NATs of 4 HER2-negative gastric cancer patients. Our analysis identified 14,622 class 1 phosphosites with 12,749 quantified phosphosites and revealed molecular changes by HER2 positivity and treatment. An inhibitory signature of the ErbB signaling was observed in the post-treatment HER2-positive T group compared with the pre-treatment HER2-positive T group. Phosphoproteomic profiles obtained by a case-by-case review using paired pre- and post-treatment HER2-positive T could be utilized to discover predictive or resistant biomarkers. Furthermore, these data nominated therapeutic kinase targets which were exclusively activated in the patient unresponded to the treatment. The present study suggests that a phosphoproteomic analysis of endoscopic biopsy specimens provides information on dynamic molecular changes which can individually characterize biologic features upon drug treatment and identify therapeutic targets in stage IV gastric cancer.

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“…[ 24 ] HSP90AA1 has ability to bind and hydrolyze ATP, which is essential for its chaperone function. [ 25 ] HSP90AA1 is also identified by Zeng [ 26 ] as a DEG of breast cancer. However, Jarzab et al [ 27 ] thinks that it is low express in breast cancer, it was just the opposite of the results of our analysis.…”

Section: Discussionmentioning

confidence: 99%

KEGG-expressed genes and pathways in triple negative breast cancer

Chen¹,

Liu²,

Cen³

et al. 2020

Medicine

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Background: The incidence of triple negative breast cancer (TNBC) is at a relatively high level, and our study aimed to identify differentially expressed genes (DEGs) in TNBC and explore the key pathways and genes of TNBC. Methods: The gene expression profiling (GSE86945, GSE86946 and GSE102088) data were obtained from Gene Expression Omnibus Datasets, DEGs were identified by using R software, Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of DEGs were performed by the Database for Annotation, Visualization and Integrated Discovery (DAVID) tools, and the protein-protein interaction (PPI) network of the DEGs was constructed by the STRING database and visualized by Cytoscape software. Finally, the survival value of hub DEGs in breast cancer patients were performed by the Kaplan–Meier plotter online tool. Results: A total of 2998 DEGs were identified between TNBC and health breast tissue, including 411 up-regulated DEGs and 2587 down-regulated DEGs. GO analysis results showed that down-regulated DEGs were enriched in gene expression (BP), extracellular exosome (CC), and nucleic acid binding, and up-regulated were enriched in chromatin assembly (BP), nucleosome (CC), and DNA binding (MF). KEGG pathway results showed that DEGs were mainly enriched in Pathways in cancer and Systemic lupus erythematosus and so on. Top 10 hub genes were picked out from PPI network by connective degree, and 7 of top 10 hub genes were significantly related with adverse overall survival in breast cancer patients ( P < .05). Further analysis found that only EGFR had a significant association with the prognosis of triple-negative breast cancer ( P < .05). Conclusions: Our study showed that DEGs were enriched in pathways in cancer, top 10 DEGs belong to up-regulated DEGs, and 7 gene connected with poor prognosis in breast cancer, including HSP90AA1 , SRC , HSPA8 , ESR1 , ACTB , PPP2CA , and RPL4 . These can provide some guidance for our research on the diagnosis and prognosis of TNBC, and further research is needed to evaluate their value in the targeted therapy of TNBC.

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Identification of key pathways and genes in response to trastuzumab treatment in breast cancer using bioinformatics analysis

Cited by 9 publications

References 63 publications

Highly heterogeneous-related genes of triple-negative breast cancer: potential diagnostic and prognostic biomarkers

Highly heterogeneous-related genes of triple-negative breast cancer: potential diagnostic and prognostic biomarkers

Temporal dynamics from phosphoproteomics using endoscopic biopsy specimens provides new therapeutic targets in stage IV gastric cancer

KEGG-expressed genes and pathways in triple negative breast cancer

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