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.

Characterization of the Relationship Between the Expression of Aspartate β-Hydroxylase and the Pathological Characteristics of Breast Cancer

“…PPARG , peroxisome proliferator-activated receptor-gamma, is an important part of the PPAR signaling pathway, which participates in tumor pathology [ 29 ]. PPARG is related to chemoresistance in BC [ 30 ], which is consistent with the survival analysis of the present study. Also, LEP expression is low in BC.…”

Prognostic significance of microsatellite instability‑associated pathways and genes in gastric cancer

“…In order to screen the functional pathways showing different expression levels between the MSI-H, MSI-L and MSI-S samples, the pathway deviation scores of potential KEGG pathways were calculated based on the enriched genes in each potential pathway ( 19 ): …”

Beyond TCR Signaling: Emerging Functions of Lck in Cancer and Immunotherapy

“…Lck expression was detected in a number of solid cancers including breast cancer [113,114,115,116], colon cancer [117,118,119], and lung carcinoma [119,120,121]. These observations have led to the hypothesis that Lck may have cancer promoting functions and hence may represent a potential diagnostic biomarker and therapeutic target for solid cancers.…”