A comprehensive analysis of human gene expression profiles identifies stromal immunoglobulin κ C as a compatible prognostic marker in human solid tumors

Marcus Schmidt*, Birte Hellwig, Seddik Hammad, Amnah Othman, Miriam Lohr, Zonglin Chen, Daniel Boehm, Susanne Gebhard, Ilka Petry, Antje Lebrecht, Cristina Cadenas, Rosemarie Marchan, Joanna D. Stewart, Christine Solbach, Lars Holmberg, Karolina Edlund, Hanna Göransson Kultima, Achim Rody, Anders Berglund, Mats LambeAnders Isaksson, Johan Botling, Thomas Karn, Volkmar Müller, Aslihan Gerhold-Ay, Christina Cotarelo, Martin Sebastian, Ralf Kronenwett, Hans Bojar, Hans Anton Lehr, Ugur Sahin, Heinz Koelbl, Mathias Gehrmann, Patrick Micke, Jörg Rahnenführer, Jan G. Hengstler

*Corresponding author for this work
112 Citations (Scopus)


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: On the basis of receiver operating characteristic analyses, robust markers were identified from a 60-gene B cell-derived metagene and analyzed in gene expression profiles of 1,810 breast cancer; 1,056 non-small cell lung carcinoma (NSCLC); 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 with immunohistochemical costaining and confocal fluorescence microscopy. Results: We identified immunoglobulin κ 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 < 0.001). In addition, IGKC gene expression was prognostic in NSCLC 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 anovel diagnosticmarker for risk stratification in human cancer and support concepts to exploit the humoral immune response for anticancer therapy. It could be validated in several independent cohorts and carried out similarly well in RNA from fresh frozen as well as from paraffin tissue and on protein level by immunostaining.

Original languageEnglish
JournalClinical Cancer Research
Issue number9
Pages (from-to)2695-2703
Number of pages9
Publication statusPublished - 01.05.2012


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