Discovery and preliminary confirmation of novel early detection biomarkers for triple-negative breast cancer using preclinical plasma samples from the Women’s Health Initiative observational study

Li, Christopher I.; Mirus, Justin E.; Zhang, Yuzheng; Ramirez, Arturo B.; Ladd, Jon J.; Prentice, Ross L.; McIntosh, Martin W.; Hanash, Samir M.; Lampe, Paul D.

doi:10.1007/s10549-012-2204-4

Cited by 20 publications

(23 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Most of the current methods for TNBC detection are based on analysis of gene expression profiles [128, 129] or sensing of antibody array platforms [130], which are generally tedious and time consuming processes that require well-trained technical personnel in well-equipped laboratories. It is also clear that TNBCs are a diverse and heterogeneous group of tumors; a single molecule may not distinguish them.…”

Section: Resultsmentioning

confidence: 99%

Pattern-based sensing of triple negative breast cancer cells with dual-ligand cofunctionalized gold nanoclusters

Tao

Auguste

2017

Biomaterials

View full text Add to dashboard Cite

Early detection of breast cancer is a critical component in patient prognosis and establishing effective therapy regimens. Here, we developed an easily accessible yet potentially powerful sensor to detect cancer cell targets by utilizing seven dual-ligand cofunctionalized gold nanoclusters (AuNCs) as both effective cell recognition elements and signal transducers. On the basis of this AuNC multichannel sensor, we have successfully distinguished healthy, cancerous and metastatic human breast cells with excellent reproducibility and high sensitivity. Triple negative breast cancer cells (TNBCs), which exhibit low expression of the estrogen receptor, progesterone receptor, and human epidermal growth factor receptor-2, were identified. The high accuracy of the blind breast cell sample tests further validates the practical application of the sensor array. In addition, the versatility of the sensor array is further justified by identifying amongst distinct cell types, different cell concentrations and cell mixtures. Notably, the drug-resistant cancer cells can also be efficiently discriminated. Furthermore, the dual-ligand cofunctionalized AuNCs can efficiently differentiate different cells from the peripheral blood of tumor-free and tumor-bearing mice. Taken together, this fluorescent AuNCs based array provides a powerful cell analysis tool with potential applications in biomedical diagnostics.

show abstract

Section: Resultsmentioning

confidence: 99%

Pattern-based sensing of triple negative breast cancer cells with dual-ligand cofunctionalized gold nanoclusters

Tao

Auguste

2017

Biomaterials

View full text Add to dashboard Cite

show abstract

“…As such, they have been used extensively in preclinical treatment studies (18–20). Plasma samples from two specific time points, namely 6–8 weeks, representing preinvasive disease (time point #1, or TP1); and midway through the lifespan of each individual KPC mouse (time point #2, or TP2), representing early invasive adenocarcinoma, were compared to controls on an antibody array platform containing 4096 unique features (8–10). No palpable masses or clinical symptoms were evident in the cohorts at either of the two time points.…”

Section: Resultsmentioning

confidence: 99%

“…In the present study, we used our high density antibody microarray platform (8–10) customized for pancreas cancer (11), to interrogate: 1) plasma drawn at distinct time points from a highly faithful genetically engineered mouse model of pancreas cancer (12); 2) pre-diagnostic plasma from women who later succumbed to PDA; and 3) diagnostic plasma from patients. By further focusing on identified plasma membrane and secreted proteins, we identified two markers that overlapped between mouse and pre-diagnostic human datasets and that have individually been previously implicated in PDA; a third novel marker, ESR1, was identified by multiple distinct antibodies in pre-diagnostic human plasma samples.…”

Section: Introductionmentioning

confidence: 99%

Cross-Species Antibody Microarray Interrogation Identifies a 3-Protein Panel of Plasma Biomarkers for Early Diagnosis of Pancreas Cancer

Mirus

Zhang

et al. 2015

Clinical Cancer Research

Self Cite

View full text Add to dashboard Cite

Purpose Pancreatic ductal adenocarcinoma (PDA) is the fourth leading cause of cancer death in the United States and its incidence is on the rise. Advanced disease is nearly uniformly lethal, emphasizing the need to identify PDA at its earliest stages. To discover early biomarkers of PDA, we evaluated the circulating proteome in murine preinvasive and invasive plasma samples and human pre-diagnostic and diagnostic samples. Experimental Design Using a customized antibody microarray platform containing >4000 features, we interrogated plasma samples spanning preinvasive and invasive disease from a highly faithful mouse model of PDA. In parallel, we mined pre-diagnostic plasma from women in the Women’s Health Initiative (WHI) who would later succumb to PDA together with matched, cancer-free control samples. Samples collected after an establishing diagnosis of PDA were also interrogated to further validate markers. Results We identified ERBB2 and TNC in our cross-species analyses and multiple antibodies identified ESR1 in pre-diagnostic plasma from people that succumb to PDA. This 3-marker panel had an AUC of 0.86 (0.76–0.96, 95% confidence interval (CI)) for the diagnostic cohort that increased to 0.97 (0.92–1.0, 95% CI) with CA19-9 included. The 3-marker panel also had an AUC of 0.68 (0.58–0.77, 95% CI) for the pre-diagnostic cohort. Conclusions We identified potential disease detection markers in plasma up to 4 years prior to death from PDA with superior performance to CA19-9. These markers might be especially useful in high-risk cohorts to diagnose early, resectable disease, particularly in patients that do not produce CA19-9.

show abstract

“…we fabricated and applied successive iterations of array platforms to discover and validate ovarian (18,21) and breast cancer serum and plasma markers (22), as well as to identify plasma autoantigen-autoantibody complexes (26). Using this experience together with our knowledge of pancreas cancer pathogenesis, we created a customized pancreas-cancerspecific antibody microarray platform.…”

Section: Antibody Microarray Discovery Of Novel and Previously Identimentioning

confidence: 99%

“…We thus found this an ideal model to use in conjunction with a novel, high-dimensional, pancreas-cancertailored antibody microarray to assay for proteomic changes during disease progression (18,21,22). The microarray consisted of ϳ2500 antibodies and represents, to our knowledge, the largest antibody array platform produced.…”

mentioning

confidence: 99%

Spatiotemporal Proteomic Analyses during Pancreas Cancer Progression Identifies Serine/Threonine Stress Kinase 4 (STK4) as a Novel Candidate Biomarker for Early Stage Disease

Mirus

Zhang

Hollingsworth

et al. 2014

Molecular & Cellular Proteomics

Self Cite

View full text Add to dashboard Cite

Pancreas cancer, or pancreatic ductal adenocarcinoma, is the deadliest of solid tumors, with a five-year survival rate of <5%. Detection of resectable disease improves survival rates, but access to tissue and other biospecimens that could be used to develop early detection markers is confounded by the insidious nature of pancreas cancer. Mouse models that accurately recapitulate the human condition allow disease tracking from inception to invasion and can therefore be useful for studying early disease stages in which surgical resection is possible. Using a highly faithful mouse model of pancreas cancer in conjunction with a high-density antibody microarray containing ϳ2500 antibodies, we interrogated the pancreatic tissue proteome at preinvasive and invasive stages of disease. The goal was to discover early stage tissue markers of pancreas cancer and follow them through histologically defined stages of disease using cohorts of mice lacking overt clinical signs and symptoms and those with end-stage metastatic disease, respectively. A panel of seven up-regulated proteins distinguishing pancreas cancer from normal pancreas was validated, and their levels were assessed in tissues collected at preinvasive, early invasive, and moribund stages of disease. Six of the seven markers also differentiated pancreas cancer from an experimental model of chronic pancreatitis. The levels of serine/threonine stress kinase 4 (STK4) increased between preinvasive and invasive stages, suggesting its potential as a tissue biomarker, and perhaps its involvement in progression from precursor pancreatic intraepithelial neoplasia to pancreatic ductal adenocarcinoma. Immunohistochemistry of STK4 at different stages of disease revealed a dynamic expression pattern further implicating it in early tumorigenic events. Immunohistochemistry of a panel of human pancreas cancers confirmed that STK4 levels were increased in tumor epithelia relative to normal tissue. Overall, this integrated approach yielded several tissue markers that could serve as signatures of disease stage, including early (resectable), and therefore clinically meaningful, stages. Molecular & Cellular Proteomics

show abstract

Discovery and preliminary confirmation of novel early detection biomarkers for triple-negative breast cancer using preclinical plasma samples from the Women’s Health Initiative observational study

Cited by 20 publications

References 33 publications

Pattern-based sensing of triple negative breast cancer cells with dual-ligand cofunctionalized gold nanoclusters

Pattern-based sensing of triple negative breast cancer cells with dual-ligand cofunctionalized gold nanoclusters

Cross-Species Antibody Microarray Interrogation Identifies a 3-Protein Panel of Plasma Biomarkers for Early Diagnosis of Pancreas Cancer

Spatiotemporal Proteomic Analyses during Pancreas Cancer Progression Identifies Serine/Threonine Stress Kinase 4 (STK4) as a Novel Candidate Biomarker for Early Stage Disease

Contact Info

Product

Resources

About