Clinical relevance of plasma-derived exosomal long non-coding RNAs (lncRNAs) CCAT1 and XIST in colorectal cancer patients

Document Type : Original article

Authors

1 Department of Clinical Biochemistry, School of Medicine, Babol University of Medical Sciences, Babol, Iran

2 Student Research Committee, Babol University of Medical Sciences, Babol, Iran

3 Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran

4 Alimentary Tract Research Center, Clinical Sciences Research Institute, Imam Khomeini Hospital, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

5 Department of Internal Medicine, School of Medicine, Iran University of Medical Sciences, Tehran, Iran

6 Colorectal Research Center, Iran University of Medical Sciences, Tehran, Iran

Abstract

The expression level of exosomal long non-coding RNAs (lncRNAs) can be relevant for clinical diagnostic approaches. The object of our study was to evaluate the differential expression of lncRNAs colon cancer associated transcript 1 (CCAT1) and X-inactive specific transcript (XIST) in plasma exosomes of colorectal cancer (CRC) patients and investigate their potential as clinical biomarkers. In a case-control study, 62 CRC patients and 62 healthy persons were studied. Plasma exosomes were isolated by a centrifugation approach and were characterized by microscopy and western blotting. After RNA extraction and cDNA synthesis, using real-time PCR technique, the relative expression of lncRNAs was evaluated. The expression levels of lncRNA CCAT1, but not XIST, were meaningfully increased in the plasma-derived exosomes of CRC patients compared to non-cancer individuals (p= 0.001, 0.083 respectively). Further analyses revealed that the expression levels of exosomal lncRNA CCAT1 were associated with the lymphovascular invasion and tumor differentiation (p<0.05). ROC curve analysis documented a diagnostic power for lncRNA CCAT1 in CRC with a sensitivity of 79% and a specificity of 80% with an optimal cutoff point 6.5, with an area under curve (AUC)=86% and p<0.0001. Also, lncRNA XIST revealed a sensitivity of 62% and a specificity of 61% with a cutoff point 2.4, with an AUC=65%. Our findings indicated the potential of plasma-derived exosomal lncRNA CCAT1 as a non-invasive clinical indicator for the diagnosis of CRC patients.

Keywords

References

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