• Integrated microarray analytics for the discovery of gene signatures for triple-negative breast cancer

      Zaka, Masood-Ul-Hassan; Peng, Yonghong; Sutton, Chris W. (2014)
      Triple-negative breast cancers (TNBC) are clinically heterogeneous, an aggressive form of breast cancer with poor diagnosis and highly therapeutic resistant. It is urgently needed for identifying novel biomarkers with increased sensitivity and specificity for early detection and personalised therapeutic intervention. Microarray profiling offered significant advances in molecular classification but sample scarcity and cohort heterogeneity remains challenging areas. Here, we investigated diagnostics signatures derived from human triple-negative tissue. We applied REMARK criteria for the selection of relevant studies and compared the signatures gene lists directly as well as assessed their classification performance in predicting diagnosis using leave-one-out cross-validation. The cross-validation results shows excellent classification accuracy ratios using all data sets. A subset signature (17-gene) extracted from the convergence of eligible signatures have also achieved excellent classification accuracy of 89.37% across all data sets. We also applied gene ontology functional enrichment analysis to extract potentially biological process, pathways and network involved in TNBC disease progression. Through functional analysis, we recognized that these independent signatures have displayed commonalities in functional pathways of cell signaling, which play important role in the development and progression of TNBC. We have also identified five unique TNBC pathways genes (SYNCRIP, NFIB, RGS4, UGCG, LOX and NNMT), which could be important for therapeutic interventions as indicated by their close association with known drivers of TNBC and previously published experimental studies.
    • Microarray big data integrated analysis to identify robust diagnostic signature for triple negative breast cancer

      Zaka, Masood-Ul-Hassan; Peng, Yonghong; Sutton, Chris W. (2015)
      Triple negative breast cancers (TNBC) are clinically heterogeneous, an aggressive subtype with poor diagnosis and strong resistance to therapy. There is a need to identify novel robust biomarkers with high specificity for early detection and therapeutic intervention. Microarray gene expression-based studies have offered significant advances in molecular classification and identification of diagnostic/prognostic signatures, however sample scarcity and cohort heterogeneity remains area of concern. In this study, we performed integrated analysis on independent microarray big data studies and identified a robust 880-gene signature for TNBC diagnosis. We further identified 16-gene (OGN, ESR1, GPC3, LHFP, AGR3, LPAR1, LRRC17, TCEAL1, CIRBP, NTN4, TUBA1C, TMSB10, RPL27, RPS3A, RPS18, and NOSTRIN) that are associated to TNBC tissues. The 880-gene signature achieved excellent classification accuracy ratio on each independent expression data sets with overall average of 99.06%, is an indication of its diagnostic power. Gene ontology enrichment analysis of 880-gene signature shows that cell-cycle pathways/processes are important clinical targets for triple negative breast cancer. Further verification of 880-gene signature could provide additive knowledge for better understanding and future direction of triple negative breast cancer research.