Discovery of Proteins Responsible for Resistance to Three Chemotherapy Drugs in Breast Cancer Cells Using Proteomics and Bioinformatics Analysis

Abstract

Chemoresistance is a daunting obstacle to the effective treatment of breast cancer patients receiving chemotherapy. Although the mechanism of chemotherapy drug resistance has been explored broadly, the precise mechanism at the proteome level remains unclear. Especially, comparative studies between widely used anticancer drugs in breast cancer are very limited. In this study, we employed proteomics and bioinformatics approaches on chemoresistant breast cancer cell lines to understand the underlying resistance mechanisms that resulted from doxorubicin (DR), paclitaxel (PR), and tamoxifen (TAR). In total, 10,385 proteins were identified and quantified from three TMT 6-plex and one TMT 10-plex experiments. Bioinformatics analysis showed that Notch signaling, immune response, and protein re-localization processes were uniquely associated with DR, PR, and TAR resistance, respectively. In addition, proteomic signatures related to drug resistance were identified as potential targets of many FDA-approved drugs. Furthermore, we identified potential prognostic proteins with significant effects on overall survival. Representatively, PLXNB2 expression was associated with a highly significant increase in risk, and downregulation of ACOX3 was correlated with a worse overall survival rate. Consequently, our study provides new insights into the proteomic aspects of the distinct mechanisms underlying chemoresistance in breast cancer.

Biomarker Discovery for Early Diagnosis of Papillary Thyroid Carcinoma Using High-Throughput Enhanced Quantitative Plasma Proteomics

“…42 PLXNB2, as a potential prognostic marker, was highly associated with the increased risk of breast cancer. 43 PLXNB2 shows the highest mRNA expression level (median: 102.9 FPKM) in TC relative to the other 16 cancer types based on the analysis of RNA-seq data of 17 cancer types in The Cancer Genome Atlas (TCGA). However, PLXNB2 levels in serum and its potential diagnostic value in TC has not yet been reported.…”

“…PLXNB2, as a prognostic biomarker for glioma, was involved in glioma invasion and vascularization . PLXNB2, as a potential prognostic marker, was highly associated with the increased risk of breast cancer . PLXNB2 shows the highest mRNA expression level (median: 102.9 FPKM) in TC relative to the other 16 cancer types based on the analysis of RNA-seq data of 17 cancer types in The Cancer Genome Atlas (TCGA).…”

Recent Contributions of Mass Spectrometry-Based “Omics” in the Studies of Breast Cancer

“…DDA in BC proteomic and metabolomic research is used for identifying and characterizing specific molecular targets. DDA approaches have been used to analyze breast cancer cell lines or tumor tissues to identify differentially expressed proteins associated with tumor development, progression, or response to treatment. ,, DDA has also been utilized to discover potential biomarkers for breast cancer diagnosis , or prognosis by comparing proteomic profiles between cancerous and noncancerous tissues. , …”

Breast Cancer with Increased Drug Resistance, Invasion Ability, and Cancer Stem Cell Properties through Metabolism Reprogramming

“…Intrinsic variety plays crucial roles in determining the response to chemotherapy. Breast cancer cells develop chemoresistance through several mechanisms, including genetic variations, epigenetic modifications, and metabolic pathway alterations [ 9 , 10 ]. In addition to increasing the drug resistance of cancer cells, these molecular mechanisms often result in the enhancement of cancer cell growth and metastatic capacity and lead to the development of cancer stem cell properties [ 11 , 12 ].…”