Transcriptional Dysregulations of Seven Non-Differentially Expressed Genes as Biomarkers of Metastatic Colon Cancer

Abstract

Background: Colon cancer (CC) is common, and the mortality rate greatly increases as the disease progresses to the metastatic stage. Early detection of metastatic colon cancer (mCC) is crucial for reducing the mortality rate. Most previous studies have focused on the top-ranked differentially expressed transcriptomic biomarkers between mCC and primary CC while ignoring non-differentially expressed genes. Results: This study proposed that the complicated inter-feature correlations could be quantitatively formulated as a complementary transcriptomic view. We used a regression model to formulate the correlation between the expression levels of a messenger RNA (mRNA) and its regulatory transcription factors (TFs). The change between the predicted and real expression levels of a query mRNA was defined as the mqTrans value in the given sample, reflecting transcription regulatory changes compared with the model-training samples. A dark biomarker in mCC is defined as an mRNA gene that is non-differentially expressed in mCC but demonstrates mqTrans values significantly associated with mCC. This study detected seven dark biomarkers using 805 samples from three independent datasets. Evidence from the literature supports the role of some of these dark biomarkers. Conclusions: This study presented a complementary high-dimensional analysis procedure for transcriptome-based biomarker investigations with a case study on mCC.

Computational Characterization of Undifferentially Expressed Genes with Altered Transcription Regulation in Lung Cancer

“…Secondly, the mqTrans analysis provides supporting evidence for the protein-level phenotype associations of dark biomarkers without differential expression in wet-lab studies. The YTH N6-Methyladenosine RNAbinding protein C2 (YTHDC2) is an RNA-modification 6-methyladenine (m6A) reader [62] and was detected as the dark biomarker gene of metastatic colon cancer (mCC) [63]. Liu et al observed that multiple m6A RNA methylation regulators showed differential expression in cancers except for YTHDC2 [64], and Tanabe et al filled the gap with immunohistochemistry technology, showing that YTHDC2 is positively correlated with mCC on its protein levels [65].…”