Abstract
The prevailing excitement in the scientific and medical community about ‘liquid biopsy’, a minimally invasive diagnostic involving body fluid, is understandable, since it has the possibility of detecting pre-malignant and early-stage cancers, and enables the assessment of response to treatments [1]. Supplementing previous techniques that sample circulating cell-free tumor DNA, tumor cells, and mi-crovesicles [2], a recent work has shown using RNA-seq data that tumor-educated platelets (TEP) can distinguish 228 patients with localized and metastasized tumors from 55 healthy individuals with 96% accuracy [3]. However, as demonstrated in the current work, over-expression of MET genes in non-small cell lung carcinoma (NSCLC), and HER2/ERBB2 genes in breast cancer are grossly misreported. Based on an analysis of a smaller subset of samples, it is shown that there is little, leave alone over-expression, of these genes in the samples with the specified disease. Confirmation that this is bona-fide platelet mRNA is provided by high levels of the platelet marker TMSB4X. A kmer-based method (k=32) has been used here (KEATS) to detect homologous transcripts, although the results are easily verified by a BLAST search – BLAST’ing the MET gene (Accid: NM 001127500.2) to a NSCLC sample (https://trace.ncbi.nlm.nih.gov/Traces/sra/?run=SRR1982781) shows almost no expression. This is in contrast to expected expression of the MET gene in another a NSCLC sample (SRR3475320) from another sample. Similar contradictions apply for HER2/ERBB2 genes with respect to breast cancer samples. This work emphasizes the neccessity of a more stringent verification framework for bioinformatic analyses, and raises serious doubts on using TEP as a possible ‘liquid biopsy’ candidate.