Array-based proteomics: mapping of protein circuitries for diagnostics, prognostics, and therapy guidance in cancer

Gulmann, Christian; Sheehan, Katherine M.; Kay, E.; Liotta, L. A.; Petricoin, EF

doi:10.1002/path.1958

Cited by 99 publications

(91 citation statements)

References 62 publications

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“…6B). This technology is based on the automated printing of a large number of different cell/tissue lysates onto nitrocellulose bound to histology slides and their analysis with specific antibodies (58). The basal levels of Hsp90␣ phosphorylation varied considerably between the various tumors analyzed (Fig.…”

Section: Activation Of Dna-pk By Small Dna Molecules Leads To Hsp90␣ mentioning

confidence: 99%

Heat Shock Protein 90α (Hsp90α) Is Phosphorylated in Response to DNA Damage and Accumulates in Repair Foci

Quanz

Herbette²,

Sayarath³

et al. 2012

Journal of Biological Chemistry

107

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Background: DNA damage triggers a complex signaling cascade that remains incompletely understood. Results: The essential chaperone Hsp90␣ is phosphorylated by DNA damage signaling kinases and accumulates at DNA damage sites. Conclusion: Hsp90␣ is directly involved in DNA repair. Significance: Our results provide an explanation for the radiosensitizing effect of Hsp90 inhibitors and identify phosphorylated Hsp90␣ as a potential biomarker for genetic instability.

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Section: Activation Of Dna-pk By Small Dna Molecules Leads To Hsp90␣ mentioning

confidence: 99%

Heat Shock Protein 90α (Hsp90α) Is Phosphorylated in Response to DNA Damage and Accumulates in Repair Foci

Quanz

Herbette²,

Sayarath³

et al. 2012

Journal of Biological Chemistry

107

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“…On the other hand, a screening assay based on an APC protein truncation test has recently been proposed and other studies mention the potential use of protein microarrays [2,60,62,63] . However, studies linking large protein expression patterns with clinical outcome in colorectal cancer are still in their infancy.…”

Section: Clinical Proteomics In Crcmentioning

confidence: 99%

Current status and prospects of clinical proteomics studies on detection of colorectal cancer: Hopes and fears

Noo

Tollenaar²,

Deelder³

et al. 2006

WJG

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BACKGROUNDIn order to improve early detection, monitor disease outcome and find targets for more individualised therapy, there is an urgent demand for new biomarkers in oncology. A field of recent interest is clinical proteomics, which has been reported to lead to high sensitivity and specificities for early detection of several solid tumors [1,2] . This emerging field uses mass spectrometry-based protein profiles/ patterns of easy accessible body fluids to distinguish cancer from non-cancer patients. This would offer a solution to the problem of cancer often being diagnosed in late stages, when curative resection of the diseased organ is no longer possible and the disease has already metastasized, thus dropping survival rates dramatically. However, after the initial positive announcements in early 2002, criticisms were raised about several aspects of serum proteomics. In this paper we describe the hopes and fears for the introduction of clinical proteomics for early detection of Colorectal adenocarcinoma (CRC). COLORECTAL CANCERColorectal adenocarcinoma is the third most common type of cancer and the fourth most frequent cause of death due to cancer worldwide. Worldwide almost one million new cases occur annually, amounting to 492 000 related deaths [3] . In developed countries it is the second most common type of tumor, with a lifetime risk of 5%, but its incidence and mortality is now decreasing [4,5] . Surgery is the cornerstone of therapy when the disease is confined to the bowel wall. This results in 70%-80% of patients who have tumors that, when diagnosed, can be resected with curative intent [6] . After curative surgery the five-year survival rate for patients with localised disease is 90%, decreasing to 65% in the case of metastasized disease to the lymph nodes. Adjuvant radiation therapy, chemotherapy, or both are useful in selected patients. Classification of tumors into pathogenetical subtypes with distinct clinical courses enables clinicians to target therapy. For CRC, the TNM staging system remains the gold standard and relies entirely on the morphological appearance of the tumor. However, tumors with similar histopathological characteristics may have different clinical outcomes and responsiveness to therapy [7] . Therefore, more individualised treatment would benefit the patient and may avoid unnecessary morbidity. Nonetheless, early detection of CRC will increase survival the most, in view of the fact that it is well recognized that CRC arises from a multistep sequence of genetic alterations that result EDITORIAL Current status and prospects of clinical proteomics studies on AbstractColorectal adenocarcinoma (CRC) is the third most common type of cancer and the fourth most frequent cause of death due to cancer worldwide. Given the natural history of CRC, early diagnosis appears to be the most appropriate tool to reduce disease-related mortality. A field of recent interest is clinical proteomics, which was reported to lead to high sensitivity and specificities for early detection of several solid...

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“…Lysates from A431 cell lines (7EGF stimulation; BD Pharmingen, San Diego, CA, USA) as well as a reference lysate prepared from several tissue specimens from multiple cases included in the study. For a detailed discussion of the technique, please see recent review (Gulmann et al, 2006).…”

Section: Patient Samplesmentioning

confidence: 99%

“…(Adobe, San Jose, CA, USA) on a UMAX PowerLook III scanner (UMAX, Dallas, TX, USA) as 16-bit TIFF images at 600 d.p.i. The TIFF images were analysed using MicroVigene software (VigeneTech, Boston, MA, USA) (this is discussed in a recent review, Gulmann et al, 2006). Briefly, the slopes for the dilution curve of each case were plotted.…”

Section: Image Analysismentioning

confidence: 99%

Signal pathway profiling of epithelial and stromal compartments of colonic carcinoma reveals epithelial-mesenchymal transition

et al. 2007

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Molecular crosstalk, including reciprocal stimulation, is theorized to take place between epithelial cancer cells and surrounding non-neoplastic stromal cells. This is the rationale for stromal therapy, which could eliminate support of a cancer by its genetically stable stroma. Epithelial-stromal crosstalk is so far poorly documented in vivo, and cell cultures and animal experiments may not provide accurate models. The current study details stromal-epithelial signalling pathways in 35 human colon cancers, and compares them with matched normal tissues using quantitative proteomic microarrays. Lysates prepared from separately microdissected epithelium and stroma were analysed using antibodies against 61 cell signalling proteins, most of which recognize activated phosphoisoforms. Analyses using unsupervised and supervised statistical methods suggest that cell signalling pathway profiles in stroma and epithelium appear more similar to each other in tumours than in normal colon. This supports the concept that coordinated crosstalk occurs between epithelium and stroma in cancer and suggests epithelialmesenchymal transition. Furthermore, the data herein suggest that it is driven by cell proliferation pathways and that, specifically, several key molecules within the mitogen-activated protein kinase pathway may play an important role. Given recent findings of epithelialmesenchymal transition in therapy-resistant tumour epithelium, these findings could have therapeutic implications for colon cancer.

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Array-based proteomics: mapping of protein circuitries for diagnostics, prognostics, and therapy guidance in cancer

Cited by 99 publications

References 62 publications

Heat Shock Protein 90α (Hsp90α) Is Phosphorylated in Response to DNA Damage and Accumulates in Repair Foci

Heat Shock Protein 90α (Hsp90α) Is Phosphorylated in Response to DNA Damage and Accumulates in Repair Foci

Current status and prospects of clinical proteomics studies on detection of colorectal cancer: Hopes and fears

Signal pathway profiling of epithelial and stromal compartments of colonic carcinoma reveals epithelial-mesenchymal transition

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