Identification of potential inflammatory breast cancer biomarkers by comprehensive TGIRT-seq profiling of RNAs in tumor and blood samples
Inflammatory breast cancer (IBC) is the most lethal breast cancer subtype, but lags in biomarker identification due to lack of large, discrete tumors. Here, we used TGIRT-seq to comprehensively profile coding and non-coding RNAs in tumors, PBMCs, and plasma from IBC and non-IBC patients and healthy donors. Besides RNAs from known IBC-relevant genes, we identified hundreds of other over-expressed coding and non-coding RNAs in IBC (p<=0.001), including subsets with elevated intron-to-exon depth ratios (IDRs) that may result from enhanced transcription resulting in accumulation of unspliced pre-mRNAs. Potential IBC biomarkers in plasma included T-cell receptor pre-mRNA fragments traced to IBC tumors and PBMCs; intron RNA fragments correlated with high IDR genes; and RNA fragments from LINE-1 and other retroelements, which are globally activated in IBC. Our findings provide new insights into IBC, define a new bioinformatic parameter relevant to RNA splicing, and demonstrate advantages of broadly analyzing transcriptomes for biomarker identification.