Evaluation of plasma circ_0006282 as a novel diagnostic biomarker in colorectal cancer

J Clin Lab Anal. 2022 Jan;36(1):e24147. doi: 10.1002/jcla.24147. Epub 2021 Dec 3.


Background: Nowadays, non-invasive and rapid detection of cancers through molecular biomarkers has received much attention. Therefore, this study investigated the non-invasive and rapid diagnosis of colorectal cancer through one of the newest biomarkers (circular RNA).

Methods: For this purpose, we collected tumoral, adjacent normal tissue, and plasma samples from 100 colorectal cancer (CRC) patients, 25 postoperative CRC patients, 28 colitis patients, and 108 healthy donors. First Illumina high-throughput (Hi Seq 2000) sequencing was performed to identify known and novel differentially expressed circRNAs in the cancerous and adjacent normal tissues (n = 3). We used quantitative real-time fluorescent polymerase chain reaction (qRT-PCR) to detect the expression level of hsa_circ_0006282 among the different samples. Moreover, inter- and intra-assays were performed to evaluate the potential of hsa_circ_0006282 as being a biomarker. The receiver operating characteristic curve (ROC) was drawn to appraise its diagnostic efficacy, and the sensitivity of this circ RNA was evaluated.

Results: Based on RNA-sequencing results circ_0006282, cirs7, circ-0001313, circ_0055625, circ_000984, circ_0055625, circ_0001178, circ_0071589, circ-001569 were upregulated, and circ-ITGA7, circ-CDYL, circITCH, circ_0026344, circ_0000038, circ_0002220, circ_0067480, circIGHV3-20-1, circ_104916, circ_0009361 were downregulated circRNA. The hsa_circ_0006282 was the highest upregulated differentially expressed circRNA. Expression evaluation of this circRNA on different samples showed upregulation in CRC tissues (p < 0.0001) and plasma samples of CRC patients in comparison to healthy controls (p < 0.0001), while the area under the curve (AUC) was 0.831 (95% CI: 0.779-0.883). Expression of hsa_circ_0006282 in CRC patients decreased to normal after surgery (p < 0.0001). Our results showed high specificity and sensitivity of CRC detection when hsa_circ_0006282, carcinoembryonic antigen (CEA), and carbohydrate antigen199 (CA199) are combined.

Conclusion: Plasma hsa_circ_0006282 can be used as a novel diagnostic and dynamic monitoring biomarker in CRC patients.

Keywords: biomarker; circular RNA; colorectal cancer; hsa_circ_0006282; real-time polymerase chain reaction.