igk and Colorectal-Neoplasms

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.

Topics: B-Lymphocytes; Biomarkers, Tumor; Breast Neoplasms; Carcinoma, Non-Small-Cell Lung; Cohort Studies; Colorectal Neoplasms; Female; Follow-Up Studies; Gene Expression Profiling; Humans; Immunoenzyme Techniques; Immunoglobulins; Lung Neoplasms; Ovarian Neoplasms; Paraffin Embedding; Prognosis; Stromal Cells

The stromal immunoglobulin kappa chain (IGKC) has been validated as an immunologic biomarker of prognosis and response to therapy in human breast cancer and other cancers. This validation emphasizes the key role of humoral immunity in control of cancer progression and has major implications for determining prognosis of patients with cancer.

Topics: Biomarkers, Tumor; Breast Neoplasms; Carcinoma, Non-Small-Cell Lung; Colorectal Neoplasms; Female; Gene Expression Profiling; Humans; Immunoglobulins; Ovarian Neoplasms

Aberrant expression of immunoglobulin (Ig) by cancer cells has been documented in a number of malignant tumors but its biological significance is unclear. Cancer cells overexpress anti-apoptotic molecules such as Bcl-xL. The present study aimed to examine the role of expression of Ig light-chain Igk and Iglambda in maintaining the high levels of Bcl-xL in colorectal cancer cells.. Thirty patients with colorectal cancer were recruited to this study. Expression of Igk, Iglambda and Bcl-xL in surgically removed cancer tissue was examined by immunohistochemistry and/or flow cytometry. Using the HT29 cell line as a study platform, RNA interference (RNAi) was employed to knock out the genes of Igk and Iglambda in the cancer cell line; the expression of Bcl-xL in HT29 cells was subsequently analyzed.. Human colorectal cancer cells, but not normal colorectal tissue, expressed both Igk and Iglambda in the cytoplasm. High levels of Bcl-xL were detected in cancer cells. Using RNAi to knock out the genes of Igk and/or Iglambda, Bcl-xL expression in HT29 cells was significantly suppressed and the cells became apoptotic.. The results suggest that expression of Igk and Iglambda is required to stabilize Bcl-xL expression in cancer cells.

Topics: Adult; Aged; bcl-X Protein; Biomarkers, Tumor; Blotting, Western; Colorectal Neoplasms; Female; Flow Cytometry; Humans; Immunoglobulin lambda-Chains; Immunoglobulins; Immunohistochemistry; Immunologic Factors; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Staging