A Comprehensive Analysis of Human Gene Expression Profiles Identifies Stromal Immunoglobulin κ C as a Compatible Prognostic Marker in Human Solid Tumors

被引：196

作者：

Schmidt, Marcus ^{[1
]}

Hellwig, Birte ^{[6
]}

Hammad, Seddik ^{[7
]}

Othman, Amnah ^{[7
]}

Lohr, Miriam ^{[6
]}

Chen, Zonglin ^{[1
]}

Boehm, Daniel ^{[1
]}

Gebhard, Susanne ^{[1
]}

Petry, Ilka ^{[1
]}

Lebrecht, Antje ^{[1
]}

Cadenas, Cristina ^{[7
]}

Marchan, Rosemarie ^{[7
]}

Stewart, Joanna D. ^{[7
]}

Solbach, Christine ^{[1
]}

Holmberg, Lars ^{[8
,9
,12
]}

Edlund, Karolina ^{[10
]}

Kultima, Hanna Goransson ^{[11
]}

Rody, Achim ^{[13
]}

Berglund, Anders ^{[8
,14
]}

Lambe, Mats ^{[7
,8
]}

Isaksson, Anders ^{[11
]}

Botling, Johan ^{[10
]}

Karn, Thomas ^{[15
]}

Mueller, Volkmar ^{[13
]}

Gerhold-Ay, Aslihan ^{[2
]}

Cotarelo, Christina ^{[3
]}

Sebastian, Martin ^{[4
]}

Kronenwett, Ralf ^{[16
]}

Bojar, Hans ^{[17
]}

Lehr, Hans-Anton ^{[18
]}

Sahin, Ugur ^{[5
]}

Koelbl, Heinz ^{[1
]}

Gehrmann, Mathias ^{[19
]}

Micke, Patrick ^{[10
]}

Rahnenfuehrer, Joerg ^{[6
]}

Hengstler, Jan G. ^{[7
]}

机构：

[1] Univ Hosp, Dept Obstet & Gynecol, D-55131 Mainz, Germany

[2] Univ Hosp, Dept Med Biometry, D-55131 Mainz, Germany

[3] Univ Hosp, Dept Pathol, D-55131 Mainz, Germany

[4] Univ Hosp, Dept Hematol & Oncol, D-55131 Mainz, Germany

[5] Med Univ Mainz, TRON Translat Oncol, Mainz, Germany

[6] Tech Univ, Dept Stat, Dortmund, Germany

[7] Leibniz Res Ctr Working Environm & Human Factors, Dortmund Tu, Germany

[8] Uppsala Univ, Reg Oncol Ctr, Uppsala, Sweden

[9] Uppsala Univ, Dept Surg Sci, Uppsala, Sweden

[10] Uppsala Univ, Dept Genet & Pathol, Uppsala, Sweden

[11] Uppsala Univ, Dept Med Sci, Sci Life Lab, Uppsala, Sweden

[12] Kings Coll London, Sch Med, Div Canc Studies, London, England

[13] Univ Hosp, Dept Obstet & Gynecol, Homburg, Germany

[14] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden

[15] Univ Hosp, Dept Obstet & Gynecol, Frankfurt, Germany

[16] Sividon Diagnost GmbH, Cologne, Germany

[17] Univ Dusseldorf, Dept Chem Oncol, Dusseldorf, Germany

[18] Univ Lausanne, Dept Pathol, Lausanne, Switzerland

[19] Bayer GmbH, Leverkusen, Germany

来源：

CLINICAL CANCER RESEARCH | 2012年 / 18卷 / 09期

关键词：

BREAST-CANCER; IMMUNE-RESPONSE; T-CELLS; B-CELLS; SIGNATURE; SURVIVAL; PROLIFERATION; METASTASIS; CARCINOMAS; INFILTRATION;

D O I：

10.1158/1078-0432.CCR-11-2210

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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 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 < 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 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. Clin Cancer Res; 18(9); 2695-703. (C)2012 AACR.

引用

页码：2695 / 2703

页数：9

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