Cell-free circulating tumor RNAs in plasma as the potential prognostic biomarkers in colorectal cancer
Nana Jin, Chau-Ming Kan, Xiao M. Pei, Wing Lam Cheung, Simon S.M. Ng, Heong Ting Wong, Hennie Yuk-Lin Cheng, Wing Wa Leung, Yee Ni C. Wong, Hin Fung Tsang, Amanda Chan, Yin Kwan Wong, William C. Cho, John Kwok Cheung Chan, William Chi Shing Tai, Ting‐Fung Chan, Sze Chuen Cesar Wong, Aldrin Kay‐Yuen Yim, Allen Chi-Shing Yu
Abstract
Background: Cell free RNA (cfRNA) contains transcript fragments from multiple cell types, making it useful for cancer detection in clinical settings. However, the pathophysiological origins of cfRNAs in plasma from colorectal cancer (CRC) patients remain unclear. Methods: To identify the tissue-specific contributions of cfRNAs transcriptomic profile, we used a published single-cell transcriptomics profile to deconvolute cell type abundance among paired plasma samples from CRC patients who underwent tumor-ablative surgery. We further validated the differentially expressed cfRNAs in 5 pairs of CRC tumor samples and adjacent tissue samples as well as 3 additional CRC tumor samples using RNA-sequencing. Results: expression was consistent across cfRNA and tissue samples. Using the Cancer Genome Atlas (TCGA) CRC datasets, we were able to classify the patients into two groups with significantly different survival outcomes. Conclusions: The three-gene signature holds promise in applying minimal residual disease (MRD) testing, which involves profiling remnants of cancer cells after or during treatment. Biomarkers identified in the present study need to be validated in a larger cohort of samples in order to ascertain their possible use in early diagnosis of CRC.