Diagnostic and prognostic potential of circulating micrornas miR-1301-3p, miR-106A-5p, miR-129-5p, miR-3613-3p, miR-647 in gastric cancer

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Abstract

Gastric cancer (GC) is one of the most common malignant tumors worldwide and ranks fifth in the structure of cancer mortality. MicroRNAs are involved in the pathogenesis and progression of GC as epigenetic factors, and are considered as potential noninvasive markers. We selected microRNAs involved in the regulation of epigenetic mechanisms in GC (miR-1301-3p, miR-106a-5p, miR-129-5p, miR-3613-3p, miR-647) and analyzed their expression in plasma of GC patients. To assess their diagnostic and prognostic potential, we estimated correlations of differential expression with the clinical and pathological characteristics of GC tumors. The study included 65 plasma samples from GC patients and 48 plasma samples obtained from individuals without tumor lesions, which were used as a control group. The expression was analyzed by using the reverse transcription polymerase chain reaction (RT-PCR) method. When comparing the expression levels of selected microRNAs in the plasma of GC patients and the control group, significant differences were found for miR-1301-3p (p = 0.04), miR-106a-5p (p = 0.029), miR-129-5p (p < 0.0001), miR-647 (p < 0.0001). MiR-129-5p expression was significantly associated with the prevalence of a primary tumor (p = 0.002), with the development of metastases to regional lymph nodes (p = 0.003) and distant metastases (p = 0.003), as well as a late clinical stage (p = 0.003). There was a significant correlation between miR-3613-3p expression and the clinical stage of GC (p = 0.049). ROC analysis revealed that combining miR-106a-5p, miR-129-5p, miR-1301-3p and miR-647 improves the diagnostic and prognostic properties of a potential panel of markers.

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About the authors

I. V. Bure

I. M. Sechenov First Moscow State Medical University (Sechenov University); Russian Medical Academy of Continuous Professional Education

Author for correspondence.
Email: bureira@mail.ru
Russian Federation, 119435 Moscow; 125993 Moscow

E. A. Vetchinkina

I. M. Sechenov First Moscow State Medical University (Sechenov University)

Email: bureira@mail.ru
Russian Federation, 119435 Moscow

A. I. Kalinkin

Research Centre for Medical Genetics

Email: bureira@mail.ru
Russian Federation, 115478 Moscow

E. B. Kuznetsova

I. M. Sechenov First Moscow State Medical University (Sechenov University); Research Centre for Medical Genetics

Email: bureira@mail.ru
Russian Federation, 119435 Moscow; 115478 Moscow

A. E. Kiseleva

I. M. Sechenov First Moscow State Medical University (Sechenov University)

Email: bureira@mail.ru
Russian Federation, 119435 Moscow

E. A. Alekseeva

I. M. Sechenov First Moscow State Medical University (Sechenov University); Research Centre for Medical Genetics

Email: bureira@mail.ru
Russian Federation, 119435 Moscow; 115478 Moscow

N. S. Esetov

I. M. Sechenov First Moscow State Medical University (Sechenov University)

Email: bureira@mail.ru
Russian Federation, 119435 Moscow

M. V. Nemtsova

I. M. Sechenov First Moscow State Medical University (Sechenov University); Research Centre for Medical Genetics

Email: bureira@mail.ru
Russian Federation, 119435 Moscow; 115478 Moscow

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2. Fig. 1. The level of miR-1301-3p (a), miR-106a-5p (b), miR-129-5p (c), miR-647 (d) and miR-3613-3p (e) representation in plasma samples of patients with gastric cancer relative to plasma samples of healthy controls. Statistically significant p values are marked with an asterisk.

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3. Fig. 2. Associations between miR-106a-5p, miR-129-5p, miR-3613-3p, miR-1301-3p, miR-647 in groups of patients with gastric cancer and healthy donors, as well as combinations of microRNAs that showed the best result (miR-129-5p, miR-1301-3p, miR-647). Receiver operating characteristic curves (ROC curves)

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4. Fig. 3. Associations of miR-106a-5p, miR-129-5p, miR-3613-3p, miR-1301-3p, miR-647 with clinicopathological characteristics of patients with GC, as well as combinations of microRNAs that showed the best result: miR-106a-5p, miR-129-5p, miR-647 with the prevalence of the primary tumor (a), miR-106a-5p, miR-129-5p, miR-647 with the development of metastases to regional lymph nodes (b), miR-106a-5p, miR-129-5p with the development of distant metastases (c), miR-106a-5p, miR-647 with signet ring cells (d); miR-106a-5p, miR-129-5p, miR-647 with clinical stage of disease (d). Receiver operating characteristic curves (ROC curves)

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5. Fig. 4. Target genes for selected microRNAs involved in epigenetic regulation (genes associated with DNA methylation are highlighted in red, genes regulating histone protein modifications are highlighted in blue, and genes regulating chromatin remodeling are highlighted in green)

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