Dataset Information

Plasma miRNA can detect colorectal cancer, but how early?

ABSTRACT: Colorectal cancer (CRC) is a major cause of deaths worldwide but has a good prognosis if detected early. The need for efficient, preferable non- or minimally invasive, inexpensive screening tools is therefore critical. We analyzed 12 miRNAs in pre- and postdiagnostic plasma samples to evaluate their potential as CRC screening markers. We used a unique study design with two overlapping cohorts, allowing analysis of pre- and postdiagnostic samples from 58 patients with CRC and matched healthy controls. Plasma concentrations of miR-15b, -16, -18a, -19a, 21, -22, -25, -26a, -29c, -142-5p, -150, and -192 were measured by semi-quantitative real-time PCR. Concentrations of miR-18a, -21, -22, and -25 in plasma from patients with CRC were significantly altered compared to healthy controls. Combined as a multimarker panel, they detected CRC with an AUC of 0.93. Furthermore, levels of these three miRNAs also showed different levels in the prediagnostic case samples close to diagnosis. Only miR-21-levels were elevated several years before diagnosis. Plasma levels of miR-18a, -21, -22, and -25 show promise as screening biomarkers for CRC. However, based on our unique analysis of prediagnostic and postdiagnostic samples from the same patients, we conclude that circulating miRNAs elevated at diagnosis may not automatically be suitable for CRC screening, if the increase occurs too close to clinical diagnosis.

SUBMITTER: Wikberg ML

PROVIDER: S-EPMC5943420 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Plasma miRNA can detect colorectal cancer, but how early?

Wikberg Maria L ML Myte Robin R Palmqvist Richard R van Guelpen Bethany B Ljuslinder Ingrid I

Cancer medicine 20180323 5

Colorectal cancer (CRC) is a major cause of deaths worldwide but has a good prognosis if detected early. The need for efficient, preferable non- or minimally invasive, inexpensive screening tools is therefore critical. We analyzed 12 miRNAs in pre- and postdiagnostic plasma samples to evaluate their potential as CRC screening markers. We used a unique study design with two overlapping cohorts, allowing analysis of pre- and postdiagnostic samples from 58 patients with CRC and matched healthy cont ...[more]

PMID: 29573205

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Project description:An increasing number of studies suggest the implication of microRNAs (miRNAs) in colorectal (CRC) carcinogenesis and disease progression. Nevertheless, the basic mechanism is not yet clear. We determined plasma miRNA expression levels using Agilent microarray technology followed by overlapping with The Cancer Genome Atlas (TCGA) tissue data and a qRT-PCR validation step and analysis of the altered miRNA signatures to emphasize new mechanistic insights. For TGCA dataset, we identified 156 altered miRNAs (79 downregulated and 77 upregulated) in colorectal tissue samples versus normal tissue. The microarray experiment is based on 16 control samples, 38 CRC plasma samples from colorectal cancer patients who have not undergone chemotherapy, and 17 chemo-treated samples. In the case of the analysis of CRC cancer versus healthy control we identified 359 altered miRNAs (214 downregulated and 60 upregulated), considering as the cutoff value a fold-change of ±1.5 and p < 0.01. An additional microarray analysis was performed on plasma from untreated colorectal cancer (n = 38) and chemotherapy-treated colorectal cancer patients (n = 17), which revealed 15 downregulated miRNAs and 53 upregulated miRNAs, demonstrating that the plasma miRNA pattern is affected by chemotherapy and emphasizing important regulators of drug resistance mechanisms. For the validation of the microarray data, we selected a panel of 4 miRNAs from the common miRNA signatures for colon and rectal cancer (miR-642b-3p, miR-195-5p and miR-4741). At the tissue level, the expression levels were in agreement with those observed in colorectal plasma. miR-1228-3p, the top upregulated miRNA in CRC, was chosen to be validated on tissue and plasma samples, as it was demonstrated to be downregulated at tissue level in our patient cohort. This was confirmed by TCGA data and was one example of ta ranscript that has a different expression level between tumor tissue and plasma. Developing more efficient investigation methods will help explain the mechanisms responsible for miRNAs released in biofluids, which is the most upregulated transcript in colorectal plasma samples and which can function as a prediction tool within the oncological field.

Dataset Information

Plasma miRNA can detect colorectal cancer, but how early?

Publications

Plasma miRNA can detect colorectal cancer, but how early?

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