Molecular Network Analysis using Reverse Phase Protein Microarrays for Patient Tailored Therapy

Speer, Runa; Wulfkuhle, Julia; Espina, Virginia; Aurajo, Robyn; Edmiston, Kirsten H.; Liotta, Lance A.; Petricoin, Emanuel F.

doi:10.1007/978-0-387-73898-7_13

Cited by 17 publications

(8 citation statements)

References 23 publications

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“…An alternative explanation may be that the deregulation of most targeted genes only caused posttranscriptional modifications, such as differences in the activation state of important signalling proteins, without affecting their mRNA levels. Such events cannot be measured by gene expression profiling but need to be assessed using other techniques (Korf et al, 2008;Schuchardt and Borlak, 2008;Speer et al, 2008). The analysis of the expression data of the gene set associated with a retroviral integration within NCOR2 in our cell model identified patients with ERa-positive breast cancer with different MFS (Supplementary Figure S4).…”

Section: Discussionmentioning

confidence: 99%

CITED2 and NCOR2 in anti-oestrogen resistance and progression of breast cancer

et al. 2009

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BACKGROUND: Endocrine therapies of breast cancer are effective but ultimately fail because of the development of treatment resistance. We have previously revealed several genes leading to tamoxifen resistance in vitro by retroviral insertion mutagenesis. To understand the manner in which these genes yield tamoxifen resistance, their effects on global gene expression were studied and those genes resulting in a distinct gene expression profile were further investigated for their clinical relevance. METHODS: Gene expression profiles of 69 human breast cancer cell lines that were made tamoxifen resistant through retroviral insertion mutagenesis were obtained using oligonucleotide arrays and analysed with bioinformatic tools. mRNA levels of NCOR2 and CITED2 in oestrogen receptor-positive breast tumours were determined by quantitative RT -PCR. mRNA levels were evaluated for association with metastasis-free survival (MFS) in 620 patients with lymph node-negative primary breast cancer who did not receive systemic adjuvant therapy, and with clinical benefit in 296 patients receiving tamoxifen therapy for recurrent breast cancer. RESULTS: mRNA expression profiles of most tamoxifen-resistant cell lines were strikingly similar, except for the subgroups of cell lines in which NCOR2 or CITED2 were targeted by the retrovirus. Both NCOR2 and CITED2 mRNA levels were associated with MFS, that is, tumour aggressiveness, independently of traditional prognostic factors. In addition, high CITED2 mRNA levels were predictive for a clinical benefit from first-line tamoxifen treatment in patients with advanced disease. CONCLUSIONS: Most retrovirally targeted genes yielding tamoxifen resistance in our cell lines do not impose a distinctive expression profile, suggesting that their causative role in cell growth may be accomplished by post-transcriptional processes. The associations of NCOR2 and CITED2 with outcome in oestrogen receptor-positive breast cancer patients underscore the clinical relevance of functional genetic screens to better understand disease progression, which may ultimately lead to the development of improved treatment options.

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Section: Discussionmentioning

confidence: 99%

CITED2 and NCOR2 in anti-oestrogen resistance and progression of breast cancer

et al. 2009

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“…Clinical samples from hundreds of patients can be simultaneously analyzed and compared. It offers a high‐throughput method to investigate the activation of particular signaling pathways or to validate differential expression of target protein biomarkers in different clinical cases 70. Paweletz et al first showed that pro‐survival pathways are activated at the cancer invasion front, using RPPA and LCM 71.…”

Section: Combining Lcm With Protein Arraysmentioning

confidence: 99%

Combining laser capture microdissection and proteomics: Methodologies and clinical applications

2010

Proteomics Clinical Apps

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Laser capture microdissection (LCM) has become an important tool for biomedical research. Various molecular biology techniques have been combined with LCM to reveal molecular profiles at an unprecedented tissue resolution. Proteomics is among those techniques that have proved fruitful in combination with LCM. This review provides an overview of the various proteomic techniques that have been developed for analyzing cells obtained using LCM. Methods for analyzing microdissected cells for various proteomic techniques are described and compared. In addition, various applications based on LCM and proteomics are discussed.

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“…Protein microarrays have recently demonstrated their huge potential in the field of biomarker discovery. RPPMs have been used to identify biomarker candidates in cancer patients that show changes in concentration that correlate with the state and progression of disease (15)(16)(17)(18)(19)(20). Sandwich immunoassays have proved to be an excellent method for accurately quantifying biomarker candidates.…”

Section: Protein Microarrays and Personalized Medicinementioning

confidence: 99%

Protein Microarrays for Personalized Medicine

Schneiderhan‐Marra

Joos

2010

Clinical Chemistry

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Background: Over the last 10 years, DNA microarrays have achieved a robust analytical performance, enabling their use for analyzing the whole transcriptome or for screening thousands of single-nucleotide polymorphisms in a single experiment. DNA microarrays allow scientists to correlate gene expression signatures with disease progression, to screen for disease-specific mutations, and to treat patients according to their individual genetic profiles; however, the real key is proteins and their manifold functions. It is necessary to achieve a greater understanding of not only protein function and abundance but also their role in the development of diseases. Protein concentrations have been shown to reflect the physiological and pathologic state of an organ, tissue, or cells far more directly than DNA, and proteins can be profiled effectively with protein microarrays, which require only a small amount of sample material. Content: Protein microarrays have become well-established tools in basic and applied research, and the first products have already entered the in vitro diagnostics market. This review focuses on protein microarray applications for biomarker discovery and validation, disease diagnosis, and use within the area of personalized medicine. Summary: Protein microarrays have proved to be reliable research tools in screening for a multitude of parameters with only a minimal quantity of sample and have enormous potential in applications for diagnostic and personalized medicine.

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Molecular Network Analysis using Reverse Phase Protein Microarrays for Patient Tailored Therapy

Cited by 17 publications

References 23 publications

CITED2 and NCOR2 in anti-oestrogen resistance and progression of breast cancer

CITED2 and NCOR2 in anti-oestrogen resistance and progression of breast cancer

Combining laser capture microdissection and proteomics: Methodologies and clinical applications

Protein Microarrays for Personalized Medicine

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