Abstract
BackgroundLymph node invasion is one of the most powerful clinical factors in cancer prognosis. However, molecular level signatures of their correlation are remaining poorly understood. Here, we propose a new approach, monotonically expressed gene analysis (MEGA), to correlate transcriptional patterns of lymph node invasion related genes with clinical outcome of breast cancer patients.ResultsUsing MEGA, we scored all genes with their transcriptional patterns over progression levels of lymph node invasion from 278 non-metastatic breast cancer samples. Applied on 65 independent test data, our gene sets of top 20 scores (positive and negative correlations) showed significant associations with prognostic measures such as cancer metastasis, relapse and survival. Our method showed better accuracy than conventional two class comparison methods. We could also find that expression patterns of some genes are strongly associated with stage transition of pathological T and N at specific time. Additionally, some pathways including T-cell immune response and wound healing serum response are expected to be related with cancer progression from pathway enrichment and common motif binding site analyses of the inferred gene sets.ConclusionsBy applying MEGA, we can find possible molecular links between lymph node invasion and cancer prognosis in human breast cancer, supported by evidences of feasible gene expression patterns and significant results of meta-analysis tests.
Highlights
Lymph node invasion is one of the most powerful clinical factors in cancer prognosis
Totally four gene sets of size 20 are constructed from 278 breast tumor gene expression data by applying monotonically expressed gene analysis (MEGA)
They are N-wise monotonically expressed genes (N-MEG) and T-wise monotonically expressed genes (T-MEG), which are further divided into positive and negative correlation sets. Given these four gene sets (N-MEG+, N-MEG, T-MEG+, and T-MEG-), we tested on65 independent breast cancer prognosis data sets downloaded from ONCOMINE database (See Methods for details) how much the expression values of the genes are correlated with prognostic outcomes
Summary
Lymph node invasion is one of the most powerful clinical factors in cancer prognosis. We propose a new approach, monotonically expressed gene analysis (MEGA), to correlate transcriptional patterns of lymph node invasion related genes with clinical outcome of breast cancer patients. The presence of lymph node invasion is one of the strongest indicators for prognoses of distant metastasis and survival in most cancers [1,2]. Studies of finding molecular markers using genome-wide expression profiles identified various genetic signatures for prediction of lymph node and distant metastasis [11,12,13,14,15,16,17,18,19]. The associations between conventional clinical features including tumor size, lymph node involvement and distant metastasis (TNM staging [20]) and prognosis are not yet identified in a genetic level. The existence of a common gene set for lymph node metastasis in a transcriptional level is unclear [21]
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