Gene co-expression network analysis (GCNA) can detect alterations in regulatory activities in case/control comparisons. We propose a framework to detect novel genes and networks for predicting breast cancer recurrence. Thirty-four prognosis candidate genes were selected based on a literature review. Four Gene Expression Omnibus Series (GSE) microarray datasets (n = 920) were used to create gene co-expression networks based on these candidates. We applied the framework to four comparison groups according to node (+/−) and recurrence (+/−). We identified a sub-network containing two candidate genes (LST1 and IGHM) and six novel genes (IGHA1, IGHD, IGHG1, IGHG3, IGLC2, and IGLJ3) related to B cell-specific immunoglobulin. These novel genes were correlated with recurrence under the control of node status and were found to function as tumor suppressors; higher mRNA expression indicated a lower risk of recurrence (hazard ratio, HR = 0.87, p = 0.001). We created an immune index score by performing principle component analysis and divided the genes into low and high groups. This discrete index significantly predicted relapse-free survival (RFS) (high: HR = 0.77, p = 0.019; low: control). Public tool KM Plotter and TCGA-BRCA gene expression data were used to validate. We confirmed these genes are correlated with RFS and distal metastasis-free survival (DMFS) in triple-negative breast cancer (TNBC) and general breast cancer.
ASJC Scopus subject areas
Hsu, H. M., Chu, C. M., Chang, Y. J., Yu, J. C., Chen, C. T., Jian, C. E., Lee, C. Y., Chiang, Y. T., Chang, C. W., & Chang, Y. T. (2019). Six novel immunoglobulin genes as biomarkers for better prognosis in triple-negative breast cancer by gene co-expression network analysis. Scientific Reports, 9(1), . https://doi.org/10.1038/s41598-019-40826-w