The use of an in vitro adenosine triphosphate-based chemotherapy response assay to predict chemotherapeutic response in breast cancer

The Breast ◽  
2008 ◽  
Vol 17 (1) ◽  
pp. 19-26 ◽  
Author(s):  
Hyun-Ah Kim ◽  
Cha-Kyong Yom ◽  
Byung-In Moon ◽  
Kuk-Jin Choe ◽  
Sun-Hee Sung ◽  
...  
Author(s):  
Noha Gwili ◽  
Stacey J. Jones ◽  
Waleed Al Amri ◽  
Ian M. Carr ◽  
Sarah Harris ◽  
...  

Abstract Background Breast cancer stem cells (BCSCs) are drivers of therapy-resistance, therefore are responsible for poor survival. Molecular signatures of BCSCs from primary cancers remain undefined. Here, we identify the consistent transcriptome of primary BCSCs shared across breast cancer subtypes, and we examine the clinical relevance of ITGA7, one of the genes differentially expressed in BCSCs. Methods Primary BCSCs were assessed using immunohistochemistry and fluorescently labelled using Aldefluor (n = 17). Transcriptomes of fluorescently sorted BCSCs and matched non-stem cancer cells were determined using RNA-seq (n = 6). ITGA7 expression was examined in breast cancers using immunohistochemistry (n = 305), and its functional role was tested using siRNA in breast cancer cells. Results Proportions of BCSCs varied from 0 to 9.4%. 38 genes were significantly differentially expressed in BCSCs; genes were enriched for functions in vessel morphogenesis, motility, and metabolism. ITGA7 was found to be significantly downregulated in BCSCs, and low expression significantly correlated with reduced survival in patients treated with chemotherapy, and with chemoresistance in breast cancer cells in vitro. Conclusions This study is the first to define the molecular profile of BCSCs from a range of primary breast cancers. ITGA7 acts as a predictive marker for chemotherapy response, in accordance with its downregulation in BCSCs.


2021 ◽  
Vol 27 ◽  
Author(s):  
Ai-Yan Xing ◽  
Bin Wang ◽  
Yu-Hong Li ◽  
Xu Chen ◽  
Ya-Wen Wang ◽  
...  

Background: Chemotherapy failure causes high breast cancer recurrence and poor patient prognosis. Thus, we studied a cohort of novel biomarkers to predict chemotherapeutic response in breast cancer. In this study, miRNA expression profiling was performed on 10 breast cancer punctured specimens sensitive to chemotherapy (MP grade 4, 5) and 10 chemotherapy resistant (MP grade 1). Differentially expressed miRNAs were verified by qRT-PCR in 60 initial samples, 59 validated samples and 71 independent samples. A miRNA signature was generated using a Logistic regression model. A receiver operating characteristic (ROC) test was used to assess specificity and sensitivity of single miRNA and miRNA signature. Target genes regulated by miRNAs and their involved signaling pathways were analyzed using GO enrichment and KEGG software. MiRNAs expression were separately compared with ER, PR, HER2 immunohistochemical staining and different drugs. qRT-PCR showed that the high expression of miR-23a-3p, miR-200c-3p, miR-214-3p and the low expression of miR-451a and miR-638 were closely related to chemoresistance. According to the formula for calculating the drug resistance risk, patients in the high-risk group were more likely to develop chemotherapy resistance than the low-risk group. Bioinformatics analysis showed that 5 miRNAs and target genes are mainly involved in p53, ubiquitin-mediated proteolysis, mTOR, Wnt, cells skeletal protein regulation, cell adhesion and ErbB signaling pathways. miR-451a expression was associated with ER, HER-2 status and anthracyclines. A miRNA signature of chemotherapeutic response may be clinically valuable for improving current chemotherapy regimens of individual treatment for patients with breast cancer.


2022 ◽  
Vol 11 ◽  
Author(s):  
Arutha Kulasinghe ◽  
James Monkman ◽  
Esha T. Shah ◽  
Nicholas Matigian ◽  
Mark N. Adams ◽  
...  

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer that has few effective treatment options due to its lack of targetable hormone receptors. Whilst the degree of tumour infiltrating lymphocytes (TILs) has been shown to associate with therapy response and prognosis, deeper characterization of the molecular diversity that may mediate chemotherapeutic response is lacking. Here we applied targeted proteomic analysis of both chemotherapy sensitive and resistant TNBC tissue samples by the Nanostring GeoMx Digital Spatial Platform (DSP). By quantifying 68 targets in the tumour and tumour microenvironment (TME) compartments and performing differential expression analysis between responsive and non-responsive tumours, we show that increased ER-alpha expression and decreased 4-1BB and MART1 within the stromal compartments is associated with adjuvant chemotherapy response. Similarly, higher expression of GZMA, STING and fibronectin and lower levels of CD80 were associated with response within tumour compartments. Univariate overall-survival (OS) analysis of stromal proteins supported these findings, with ER-alpha expression (HR=0.19, p=0.0012) associated with better OS while MART1 expression (HR=2.3, p=0.035) was indicative of poorer OS. Proteins within tumour compartments consistent with longer OS included PD-L1 (HR=0.53, p=0.023), FOXP3 (HR=0.5, p=0.026), GITR (HR=0.51, p=0.036), SMA (HR=0.59, p=0.043), while EPCAM (HR=1.7, p=0.045), and CD95 (HR=4.9, p=0.046) expression were associated with shorter OS. Our data provides early insights into the levels of these markers in the TNBC tumour microenvironment, and their association with chemotherapeutic response and patient survival.


Pancreas ◽  
2012 ◽  
Vol 41 (3) ◽  
pp. 498-500 ◽  
Author(s):  
Chang Moo Kang ◽  
Hyunki Kim ◽  
Yuri Cho ◽  
Yu Sun Kim ◽  
Ho Kyoung Hwang ◽  
...  

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