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Identification of Personalized Chemoresistance Genes in Subtypes of Basal-Like Breast Cancer Based on Functional Differences Using Pathway Analysis.

Wu T, Wang X, Li J, Song X, Wang Y, Wang Y, Zhang L, Li Z, Tian J - PLoS ONE (2015)

Bottom Line: Subgroups, personalized biomarkers, and therapy targets were identified using cluster analysis of differentially expressed genes.Based on functional differences among these subgroups, we identified nine biomarkers related to drug resistance: SYK, LCK, GAB2, PAWR, PPARG, MDFI, ZAP70, CIITA and ACTA1.Therefore, these nine differentially expressed genes and their associated functional pathways should provide the basis for novel personalized clinical treatments of basal-like breast cancer.

View Article: PubMed Central - PubMed

Affiliation: Department of Ultrasound, the Second Affiliated Hospital of Harbin Medical University, Harbin City, Heilongjiang Province, China.

ABSTRACT
Breast cancer is a highly heterogeneous disease that is clinically classified into several subtypes. Among these subtypes, basal-like breast cancer largely overlaps with triple-negative breast cancer (TNBC), and these two groups are generally studied together as a single entity. Differences in the molecular makeup of breast cancers can result in different treatment strategies and prognoses for patients with different breast cancer subtypes. Compared with other subtypes, basal-like and other ER+ breast cancer subtypes exhibit marked differences in etiologic factors, clinical characteristics and therapeutic potential. Anthracycline drugs are typically used as the first-line clinical treatment for basal-like breast cancer subtypes. However, certain patients develop drug resistance following chemotherapy, which can lead to disease relapse and death. Even among patients with basal-like breast cancer, there can be significant molecular differences, and it is difficult to identify specific drug resistance proteins in any given patient using conventional variance testing methods. Therefore, we designed a new method for identifying drug resistance genes. Subgroups, personalized biomarkers, and therapy targets were identified using cluster analysis of differentially expressed genes. We found that basal-like breast cancer could be further divided into at least four distinct subgroups, including two groups at risk for drug resistance and two groups characterized by sensitivity to pharmacotherapy. Based on functional differences among these subgroups, we identified nine biomarkers related to drug resistance: SYK, LCK, GAB2, PAWR, PPARG, MDFI, ZAP70, CIITA and ACTA1. Finally, based on the deviation scores of the examined pathways, 16 pathways were shown to exhibit varying degrees of abnormality in the various subgroups, indicating that patients with different subtypes of basal-like breast cancer can be characterized by differences in the functional status of these pathways. Therefore, these nine differentially expressed genes and their associated functional pathways should provide the basis for novel personalized clinical treatments of basal-like breast cancer.

No MeSH data available.


Related in: MedlinePlus

The clustering results for the basal-like subtype.A heat map was used to visualize the clustering results for basal BC. Basal BC can be divided into 4 subgroups, indicated with different colors. CR and NOCR represent sensitive and drug resistant patients, respectively.
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pone.0131183.g003: The clustering results for the basal-like subtype.A heat map was used to visualize the clustering results for basal BC. Basal BC can be divided into 4 subgroups, indicated with different colors. CR and NOCR represent sensitive and drug resistant patients, respectively.

Mentions: As this method could effectively distinguish between the luminal A and B subgroups, this method was also employed for clustering analysis using the basal-like subtype breast cancer samples to identify potential subgroups with different drug resistance mechanisms within this subtype. The clustering results for the basal-like subtype are shown in Fig 3.


Identification of Personalized Chemoresistance Genes in Subtypes of Basal-Like Breast Cancer Based on Functional Differences Using Pathway Analysis.

Wu T, Wang X, Li J, Song X, Wang Y, Wang Y, Zhang L, Li Z, Tian J - PLoS ONE (2015)

The clustering results for the basal-like subtype.A heat map was used to visualize the clustering results for basal BC. Basal BC can be divided into 4 subgroups, indicated with different colors. CR and NOCR represent sensitive and drug resistant patients, respectively.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4488356&req=5

pone.0131183.g003: The clustering results for the basal-like subtype.A heat map was used to visualize the clustering results for basal BC. Basal BC can be divided into 4 subgroups, indicated with different colors. CR and NOCR represent sensitive and drug resistant patients, respectively.
Mentions: As this method could effectively distinguish between the luminal A and B subgroups, this method was also employed for clustering analysis using the basal-like subtype breast cancer samples to identify potential subgroups with different drug resistance mechanisms within this subtype. The clustering results for the basal-like subtype are shown in Fig 3.

Bottom Line: Subgroups, personalized biomarkers, and therapy targets were identified using cluster analysis of differentially expressed genes.Based on functional differences among these subgroups, we identified nine biomarkers related to drug resistance: SYK, LCK, GAB2, PAWR, PPARG, MDFI, ZAP70, CIITA and ACTA1.Therefore, these nine differentially expressed genes and their associated functional pathways should provide the basis for novel personalized clinical treatments of basal-like breast cancer.

View Article: PubMed Central - PubMed

Affiliation: Department of Ultrasound, the Second Affiliated Hospital of Harbin Medical University, Harbin City, Heilongjiang Province, China.

ABSTRACT
Breast cancer is a highly heterogeneous disease that is clinically classified into several subtypes. Among these subtypes, basal-like breast cancer largely overlaps with triple-negative breast cancer (TNBC), and these two groups are generally studied together as a single entity. Differences in the molecular makeup of breast cancers can result in different treatment strategies and prognoses for patients with different breast cancer subtypes. Compared with other subtypes, basal-like and other ER+ breast cancer subtypes exhibit marked differences in etiologic factors, clinical characteristics and therapeutic potential. Anthracycline drugs are typically used as the first-line clinical treatment for basal-like breast cancer subtypes. However, certain patients develop drug resistance following chemotherapy, which can lead to disease relapse and death. Even among patients with basal-like breast cancer, there can be significant molecular differences, and it is difficult to identify specific drug resistance proteins in any given patient using conventional variance testing methods. Therefore, we designed a new method for identifying drug resistance genes. Subgroups, personalized biomarkers, and therapy targets were identified using cluster analysis of differentially expressed genes. We found that basal-like breast cancer could be further divided into at least four distinct subgroups, including two groups at risk for drug resistance and two groups characterized by sensitivity to pharmacotherapy. Based on functional differences among these subgroups, we identified nine biomarkers related to drug resistance: SYK, LCK, GAB2, PAWR, PPARG, MDFI, ZAP70, CIITA and ACTA1. Finally, based on the deviation scores of the examined pathways, 16 pathways were shown to exhibit varying degrees of abnormality in the various subgroups, indicating that patients with different subtypes of basal-like breast cancer can be characterized by differences in the functional status of these pathways. Therefore, these nine differentially expressed genes and their associated functional pathways should provide the basis for novel personalized clinical treatments of basal-like breast cancer.

No MeSH data available.


Related in: MedlinePlus