title: Identification of Personalized Chemoresistance Genes in Subtypes of Basal-Like Breast Cancer Based on Functional Differences Using Pathway Analysis.
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.
authors.affiliation: Department of Ultrasound, the Second Affiliated Hospital of Harbin Medical University, Harbin City, Heilongjiang Province, China.
authors.forename: Tong
authors.initials: T
authors.lastname: Wu
authors.affiliation: Department of Ultrasound, the Second Affiliated Hospital of Harbin Medical University, Harbin City, Heilongjiang Province, China.
authors.forename: Xudong
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Ultrasound, the First Hospital of Qiqihar, Qiqihar City, Heilongjiang Province, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Ultrasound, the Frontier Corps Hospital in Heilongjiang Province, Harbin City, Heilongjiang Province, China.
authors.forename: Xiuzhen
authors.initials: X
authors.lastname: Song
authors.affiliation: Department of General Surgery, the Second Hospital of Hebei Medical University, Shijiazhuang City, Hebei Province, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin City, Heilongjiang Province, China.
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Ultrasound, the Second Affiliated Hospital of Harbin Medical University, Harbin City, Heilongjiang Province, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Ultrasound, the Second Affiliated Hospital of Harbin Medical University, Harbin City, Heilongjiang Province, China.
authors.forename: Ziyao
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Ultrasound, the Second Affiliated Hospital of Harbin Medical University, Harbin City, Heilongjiang Province, China.
authors.forename: Jiawei
authors.initials: J
authors.lastname: Tian
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D016000:Cluster Analysis; D015331:Cohort Studies; D030541:Databases, Genetic; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D006801:Humans; D053858:Metabolic Networks and Pathways / Q000235:genetics; D057285:Precision Medicine; D011379:Prognosis; D011960:Receptors, Estrogen / Q000378:metabolism; D059467:Transcriptome; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D011960:Receptors, Estrogen