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Transcription profiling of human breast cancer cohort reveals the humoral immune system has a key prognostic impact in node-negative breast cancer

ABSTRACT: Estrogen receptor (ER) expression and proliferative activity are established prognostic factors in breast cancer. In a search for additional prognostic motives we analyzed the gene expression patterns of 200 tumors of patients who were not treated by systemic therapy after surgery using a discovery approach. After performing hierarchical cluster analysis, we identified co-regulated genes related to the biological process of proliferation, steroid hormone receptor expression, as well as B cell and T cell infiltration. We calculated metagenes as surrogate for all genes contained within a particular cluster and visualized the relative expression in relation to time to metastasis with principal component analysis. Distinct patterns led to the hypothesis of a prognostic role of the immune system in tumors with high expression of proliferation associated genes. In multivariate Cox regression analysis the proliferation metagene showed a significant association with metastasis-free survival of the whole discovery cohort (Hazard Ratio (HR) 2.20, 95% confidence interval (CI) 1.40-3.46). The B cell metagene showed additional independent prognostic information in carcinomas with high proliferative activity (HR 0.66, 95% CI 0.46 - 0.97). A prognostic influence of the B-cell metagene was independently confirmed by multivariate analysis in a first validation cohort enriched for high grade tumors (n=286, HR 0.78, 95% CI 0.62-0.98), and a second validation cohort enriched for younger patients (n=302, HR 0.83, 95% CI 0.7-0.97). Thus, we could demonstrate in three cohorts of untreated node-negative breast cancer patients, that the humoral immune system plays a pivotal role for metastasis-free survival of carcinomas of the breast. Experiment Overall Design: Population based N0 untreated breast cancer cohort study including 200 samples

ORGANISM(S): Homo sapiens

SUBMITTER: Mathias Gehrmann

PROVIDER: E-GEOD-11121 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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The humoral immune system has a key prognostic impact in node-negative breast cancer.

Schmidt Marcus M Böhm Daniel D von Törne Christian C Steiner Eric E Puhl Alexander A Pilch Henryk H Lehr Hans-Anton HA Hengstler Jan G JG Kölbl Heinz H Gehrmann Mathias M

Cancer research 20080701 13

Estrogen receptor (ER) expression and proliferative activity are established prognostic factors in breast cancer. In a search for additional prognostic motifs, we analyzed the gene expression patterns of 200 tumors of patients who were not treated by systemic therapy after surgery using a discovery approach. After performing hierarchical cluster analysis, we identified coregulated genes related to the biological process of proliferation, steroid hormone receptor expression, as well as B-cell and ...[more]

PMID: 18593943

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Dataset Information

Transcription profiling of human breast cancer cohort reveals the humoral immune system has a key prognostic impact in node-negative breast cancer

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The humoral immune system has a key prognostic impact in node-negative breast cancer.

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