Abstract
Although the central role of the immune system for tumor prognosis is generally accepted, a single robust marker is not yet available. 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. 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. 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.
Highlights
It has become evident that the immune response in the tumor environment plays a pivotal role in all stages of carcinogenesis and in different context may promote or inhibit tumor progression [1,2,3]
immunoglobulin k C (IGKC) was consistently associated with metastasis-free survival across different molecular subtypes in node-negative breast cancer (n 1⁄4 965) and predicted response to anthracycline-based neoadjuvant chemotherapy (n 1⁄4 845; P < 0.001)
IGKC gene expression was prognostic in non–small cell lung carcinoma (NSCLC) and colorectal cancer
Summary
It has become evident that the immune response in the tumor environment plays a pivotal role in all stages of carcinogenesis and in different context may promote or inhibit tumor progression [1,2,3]. In human cancer, this concept is supported by the observation that the presence of specific immune cells can be linked to different clinical outcomes. In breast cancer, several prognostic and predictive gene signatures reflect the individual immune response, independent from traditional markers like hormone receptor status or Ki-67 proliferation index [12,13,14]. To translate the findings to robust analytic tools for clinical diagnostics on routinely archived tissue, immunohistochemistry was applied
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