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miRNA plasma signature enables diagnosis of early onset colorectal cancer

1st September 2022

Early onset colorectal cancer can be diagnosed in blood samples using a miRNA signature and which could be used for noninvasive screening

The presence of early onset colorectal cancer can be diagnosed non-invasively using an assay based on a plasma micro RNA (miRNA) signature according to the results of a study by an international group of researchers.

The World Health Organisation estimates that in 2020, there were 1.93 million cases of cancer of the colon and rectum (colorectal cancer) and which led to 916,000 deaths. However, there is some evidence to suggest that the overall incidence of colorectal cancer (CRC) is reducing but appears to be increasing in those under 50 years of age.

For instance, one US study found that the age-adjusted CRC incidence rate decreased by 0.92% between 1975 and 2010 but also noted how for patients 20 to 34 years, the incidence rates of localised, regional, and distant colon and rectal cancers have increased during this period of time.

In fact, approximately 1 in 10 new diagnoses of CRC, termed early onset CRC (EOCRC), are now made in individuals 50 years or younger. Furthermore, there is a suggestion that early-onset carcinomas commonly show pathologic features associated with aggressive behaviour.

Consequently, it is necessary to develop a means of testing for ERCRC since a delay in the diagnosis could have a significant impact, leading to an early death.

There is accumulating evidence that circulating micro-RNAs, which are a class of non-coding RNAs that play important roles in regulating gene expression, also reflect physiological and pathological alterations in cancer patients and may serve as important surrogate minimally-invasive biomarkers.

It has already been shown that the miRNA, MiR-92 is significantly elevated in the plasma of patients with CRC and could become a potential non-invasive molecular marker for CRC screening. However, to date, there are no studies examining the potential value of miRNAs in patients with early onset colorectal cancer and in the present study, researchers set out to try and identify a suitable miRNA signature for this group of patients.

Early onset colorectal cancer and miRNA signature

The team identified 4 miRNA signature in patients with EOCRC and which had a diagnostic area under the curve (AUC) of 0.82 with a sensitivity of 0.72 and specificity of 0.84. The team tested the diagnostic potential of this 4 marker panel in plasma samples in both a training and validation cohort.

The validation cohort included 142 patients, 77 of whom had a median age of 43 years (48.1% female) and 65 control patients. The AUC was 0.88 (95% CI 0.82 – 0.93, p < 0.01) and which provided a sensitivity of 0.82 and a specificity of 0.86 and an accuracy of 84%.

In addition, the AUC for the biomarker panel was 0.92 for EOCRC in stages I/II and 0.87 for stages III/IV and could distinguish between early and later stage disease.

In an effort to show that the use of the miRNA signature was in fact discriminatory, the researchers measured levels in plasma samples of patients before and 3 months after curative surgery and found that there was a significant decrease in expression in the post-surgical samples (p < 0.05).

Finally, the team showed that the miRNA signature could also discriminate between patients with late onset CRC from non-disease control patients with an AUC of 0.84, a sensitivity of 0.82 and a specificity of 0.88.

The authors concluded that this novel miRNA signature could be used to detect patients with early onset CRC and that with further validation, could be used to transform the screening of patients with EOCRC and subsequently reduce mortality rates.

Nakamura K et al. A Liquid Biopsy Signature for the Detection of Patients with Early-Onset Colorectal Cancer Gastroenterology 2022