title: A comprehensive analysis of human gene expression profiles identifies stromal immunoglobulin κ C as a compatible prognostic marker in human solid tumors.
abstract: OBJECTIVE
  Although the central role of the immune system for tumor prognosis is generally accepted, a single robust marker is not yet available.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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 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.
authors.affiliation: Departments of Obstetrics and Gynecology, University Hospital, Mainz, Germany. marcus.schmidt@unimedizin-mainz.de
authors.forename: Marcus
authors.initials: M
authors.lastname: Schmidt
authors.forename: Birte
authors.initials: B
authors.lastname: Hellwig
authors.forename: Seddik
authors.initials: S
authors.lastname: Hammad
authors.forename: Amnah
authors.initials: A
authors.lastname: Othman
authors.forename: Miriam
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authors.lastname: Lohr
authors.forename: Zonglin
authors.initials: Z
authors.lastname: Chen
authors.forename: Daniel
authors.initials: D
authors.lastname: Boehm
authors.forename: Susanne
authors.initials: S
authors.lastname: Gebhard
authors.forename: Ilka
authors.initials: I
authors.lastname: Petry
authors.forename: Antje
authors.initials: A
authors.lastname: Lebrecht
authors.forename: Cristina
authors.initials: C
authors.lastname: Cadenas
authors.forename: Rosemarie
authors.initials: R
authors.lastname: Marchan
authors.forename: Joanna D
authors.initials: JD
authors.lastname: Stewart
authors.forename: Christine
authors.initials: C
authors.lastname: Solbach
authors.forename: Lars
authors.initials: L
authors.lastname: Holmberg
authors.forename: Karolina
authors.initials: K
authors.lastname: Edlund
authors.forename: Hanna Göransson
authors.initials: HG
authors.lastname: Kultima
authors.forename: Achim
authors.initials: A
authors.lastname: Rody
authors.forename: Anders
authors.initials: A
authors.lastname: Berglund
authors.forename: Mats
authors.initials: M
authors.lastname: Lambe
authors.forename: Anders
authors.initials: A
authors.lastname: Isaksson
authors.forename: Johan
authors.initials: J
authors.lastname: Botling
authors.forename: Thomas
authors.initials: T
authors.lastname: Karn
authors.forename: Volkmar
authors.initials: V
authors.lastname: Müller
authors.forename: Aslihan
authors.initials: A
authors.lastname: Gerhold-Ay
authors.forename: Christina
authors.initials: C
authors.lastname: Cotarelo
authors.forename: Martin
authors.initials: M
authors.lastname: Sebastian
authors.forename: Ralf
authors.initials: R
authors.lastname: Kronenwett
authors.forename: Hans
authors.initials: H
authors.lastname: Bojar
authors.forename: Hans-Anton
authors.initials: HA
authors.lastname: Lehr
authors.forename: Ugur
authors.initials: U
authors.lastname: Sahin
authors.forename: Heinz
authors.initials: H
authors.lastname: Koelbl
authors.forename: Mathias
authors.initials: M
authors.lastname: Gehrmann
authors.forename: Patrick
authors.initials: P
authors.lastname: Micke
authors.forename: Jörg
authors.initials: J
authors.lastname: Rahnenführer
authors.forename: Jan G
authors.initials: JG
authors.lastname: Hengstler
mesh_terms: D001402:B-Lymphocytes / Q000378:metabolism / Q000473:pathology; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D006801:Humans; D007124:Immunoenzyme Techniques; D007136:Immunoglobulins / Q000235:genetics* / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism; D016612:Paraffin Embedding; D011379:Prognosis; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; C014609:IgK; D007136:Immunoglobulins