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Talent & Technology

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Breast Cancer Biomarkers

Investigators at the Canary Center at Stanford are collaborating with researchers and clinicians at the Stanford Cancer Institute on a project to identify gene expression and protein changes in patient specimens as breast cancer develops, and to determine whether those changes correlate with specific imaging findings.

The team is establishing a Stanford University tissue bank of matched tumor and normal breast biopsy samples, mammography, ultrasound, magnetic resonance imaging studies, and blood samples.

The team will integrate the data and identify correlations between plasma protein and tumor gene expression profiles, pathology, and radiographic imaging studies. The dataset will represent the most comprehensive analysis of its kind to date. Potential biomarkers that signal the development of the tumor would form the basis for early detection blood tests to complement imaging.

Additional work aims to identify biomarkers that distinguish women with cancer from those with benign conditions (such as a cyst). These biomarkers would potentially reduce the number of unnecessary invasive follow-up tests and enhance the interpretation of mammographic images for early detection of breast cancer.

Magneto-Nanosensor (MNS) Array for Prostate Cancer Biomarker Evaluation

Novel biomarker assays are urgently needed to accurately discriminate benign prostatic hypertrophy (BPH) from prostate cancer (CaP) and minimize unnecessary radical prostatectomy while identifying patients with aggressive prostate cancer.

At the same time, technology that can detect panels of multiple biomarkers in very low concentrations is essential. To address these unmet needs, we developed assays for 14 target proteins and devised a magneto-nanosensor platform that can detect protein biomarkers down to attomolar concentrations. Of the 14 assays, seven met our performance criteria for additional testing and were transferred to the Bioscale ViBE platform for additional optimization and large sample set evaluation.

The assays transferred to the ViBE included the blood biomarkers free and total Prostate Specific Antigen (fPSA, tPSA), Prostatic Acid Phosphatase (PAP), Interleukin 6 Soluble Receptor (IL6-sR), Secreted Protein Acidic and Rich in Cysteine 2 (SPARC2), Carbonic Anhydrase 1 (CA1), and Spondin 2 (SPON2). We tested a sample set of 240 patient samples using optimized assays against all 8 biomarker proteins targets. For most of these targets, this was the largest clinical sample set tested to date. The most significant differences between Benign Prostate Hyperplasia (BPH) and PRCA were observed using the fPSA:tPSA (P = 3.8×10-6) and SPON2 (P = 9.2×10-7) assays. These assays also had the highest areas under the curve (AUC) in receiver operating characteristic analysis. Interestingly, IL-6sR could discriminate between Gleason 6 and 7 samples with an AUC of 0.70 — this may have future use in prognostication panels.

Based upon the results of a 240-patient serum sample set using ViBE platform, the five best-performing biomarkers, tPSA, fPSA, IL6-sR, CA1 and SPON2, were selected and the optimized ViBE assays were translated onto the magneto-nanosensor assays. A new cohort of 50 BPH and 50 PCa samples was tested on the multiplex magneto-nanosensor assay. Consistent with the 240 sample set, magneto-nanosensor assay results indicated significant differences between BPH and PRCA for fPSA:tPSA and SPON2 though SPON2 did not perform better than fPSA:tPSA alone.

Additionally, we also tested a panel of five autoantibodies on the magneto-nanosensor platform in an effort to improve the sensitivity and specificity of the blood-based detection platform. Of these, four were highly significant and had an AUC of >0.91. Based on the success of this approach to multiplex biomarkers in small sample sizes, we will continue to investigate the magneto-nanosensor platform for biomarker detection of a variety of diseases.