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A comprehensive analysis of human gene expression profiles identifies stromal immunoglobulin kappa C as a compatible prognostic marker in human solid tumors
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2012 (English)In: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 18, no 9, 2695-2703 p.Article in journal (Refereed) Published
Abstract [en]

PURPOSE:

Although the central role of the immune system for tumor prognosis is generally accepted a single robust marker is not yet available.

EXPERIMENTAL DESIGN:

Based on ROC (receiver operating characteristic) analyses robust markers were identified from a 60 gene B-cell derived metagene and analyzed in gene expression profiles of 1810 breast cancer, 1056 non-small cell lung cancer, 513 colorectal and 426 ovarian cancer patients. Protein and RNA levels were examined in paraffin embedded tissue of 330 breast cancer patients. The cell types were identified using immunohistochemical co-staining and confocal fluorescence microscopy.

RESULTS:

We identified immunoglobulin kappa C (IGKC) which as a single marker is similarly predictive and prognostic as the entire B-cell metagene. IGKC was consistently associated with metastasis free survival across different molecular subtypes in node-negative breast cancer (n=965) and predicted response to anthracycline-based neoadjuvant chemotherapy (n=845) [P less than 0.001]. In addition, IGKC gene expression was prognostic in non-small cell lung cancer and colorectal cancer. No association was observed in ovarian cancer. IGKC protein expression was significantly associated with survival in paraffin embedded tissues of 330 breast cancer patients. Tumor infiltrating plasma cells were identified as the source of IGKC expression

CONCLUSION:

Our findings provide IGKC as a novel diagnostic marker for risk stratification in human cancer and support concepts to exploit the humoral immune response for anti-cancer therapy. It could be validated in several independent cohorts and performed similarly well in RNA from fresh frozen as well as from paraffin tissue and on protein level by immunostaining.

Place, publisher, year, edition, pages
2012. Vol. 18, no 9, 2695-2703 p.
National Category
Clinical Laboratory Medicine
Research subject
Pathology
Identifiers
URN: urn:nbn:se:uu:diva-169734DOI: 10.1158/1078-0432.CCR-11-2210ISI: 000304249200030PubMedID: 22351685OAI: oai:DiVA.org:uu-169734DiVA: diva2:507602
Available from: 2012-03-05 Created: 2012-03-05 Last updated: 2017-12-07Bibliographically approved

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Holmberg, LarsEdlund, KarolinaGöransson Kultima, HannaBerglund, AndersIsaksson, AndersBotling, JohanMicke, Patrick

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