AUTHOR=Jin Nana , Kan Chau-Ming , Pei Xiao Meng , Cheung Wing Lam , Ng Simon Siu Man , Wong Heong Ting , Cheng Hennie Yuk-Lin , Leung Wing Wa , Wong Yee Ni , Tsang Hin Fung , Chan Amanda Kit Ching , Wong Yin Kwan Evelyn , Cho William Chi Shing , Chan John Kwok Cheung , Tai William Chi Shing , Chan Ting-Fung , Wong Sze Chuen Cesar , Yim Aldrin Kay-Yuen , Yu Allen Chi-Shing TITLE=Cell-free circulating tumor RNAs in plasma as the potential prognostic biomarkers in colorectal cancer JOURNAL=Frontiers in Oncology VOLUME=13 YEAR=2023 URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2023.1134445 DOI=10.3389/fonc.2023.1134445 ISSN=2234-943X 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

The transcriptomic component from intestinal secretory cells was significantly decreased in the in-house post-surgical cfRNA. The HPGD, PACS1, and TDP2 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.