Early detection of colorectal cancer is the main prerequisite for successful treatment and reduction of mortality. Circulating microRNAs were previously identified as promising diagnostic, prognostic and predictive biomarkers. The purpose of this study was to identify serum microRNAs enabling early diagnosis and prognosis prediction of colon cancer. In total, serum samples from 427 colon cancer patients and 276 healthy donors were included in three-phase biomarker study. Large-scale microRNA expression profiling was performed using Illumina small RNA sequencing. Diagnostic and prognostic potential of identified microRNAs was validated on independent training and validation sets of samples using RT-qPCR. Fifty-four microRNAs were found to be significantly deregulated in serum of colon cancer patients compared to healthy donors (P < 0.01). A diagnostic four-microRNA signature consisting of miR-23a-3p, miR-27a-3p, miR-142-5p and miR-376c-3p was established (AUC = 0.917), distinguishing colon cancer patients from healthy donors with sensitivity of 89% and specificity of 81% (AUC = 0.922). This panel of microRNAs exhibited high diagnostic performance also when analyzed separately in colon cancer patients in early stages of the disease (T1-4N0M0; AUC = 0.877). Further, a prognostic panel based on the expression of miR-23a-3p and miR-376c-3p independent of TNM stage was established (HR 2.30; 95% CI 1.44-3.66; P < 0.0004). In summary, highly sensitive signatures of circulating microRNAs enabling non-invasive early detection and prognosis prediction of colon cancer were identified.
- MeSH
- časná detekce nádoru MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikro RNA krev MeSH
- nádorové biomarkery krev MeSH
- nádory tračníku krev genetika patologie MeSH
- prognóza MeSH
- regulace genové exprese u nádorů MeSH
- senioři MeSH
- staging nádorů MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Primary tumor spread to the liver is the major cause of disease progression and death in patients with colorectal cancer (CRC). MicroRNAs (miRNAs) are small non-coding RNAs that are involved in cancer development and progression, but their role in metastasis has not been extensively investigated. MATERIALS AND METHODS: Firstly, expression profiling of 752 miRNAs in 20 primary tumors and their corresponding liver metastases was performed. Secondly, validation of the results was carried out on an independent cohort of 66 patients with metastatic CRC using reverse transcription-quantitative polymerase chain (RT-qPCR) reaction. RESULTS: In total, 33 miRNAs were found to be significantly deregulated in liver metastases compared to their primary tumors. Fifteen miRNAs were chosen for subsequent validation, which confirmed significantly reduced expression of miR-143, miR 10b, and miR-28-5p, and increased expression of miR 122, miR-122*, and miR 885-5p in the tissue of liver metastases. CONCLUSION: These results indicate that miRNAs could serve as new therapeutic targets in patients with metastatic CRC.
- MeSH
- celogenomová asociační studie * MeSH
- dospělí MeSH
- kolorektální nádory genetika patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikro RNA genetika MeSH
- nádory jater sekundární MeSH
- regulace genové exprese u nádorů MeSH
- reprodukovatelnost výsledků MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- shluková analýza MeSH
- stanovení celkové genové exprese * MeSH
- transkriptom MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Závěrečná zpráva o řešení grantu Interní grantové agentury MZ ČR
1 svazek : ilustrace, tabulky ; 30 cm
Our study is based on methodically novel and progressive approach based on microRNAs to identify cancer biomarkers in blood serum. The rationale of our project is to build diagnostic panel of microRNAs enabling early detection of CRC in asymptomatic patients for screening purposes or monitoring of CRC patients with hereditary syndroms, as well as sensitive detection of disease progression in follow-up of CRC patients.
Naše studie je založena na metodicky novém a progresivním, na mikroRNA založeném, přístupu identifikace biomarkerů nádorových onemocnění v krevním séru. Předmětem řešení projektu je vytvoření diagnostického panelu cirkulujících mikroRNA umožňujícího časný záchyt CRC u asymptomatických pacientů ať již pro screeningové účely, nebo sledování pacientů s hereditárními formami CRC, a dále citlivý záchyt progrese onemocnění v rámci sledování pacientů s CRC podstupujících adjuvantní terapeutické režimy.
- MeSH
- časná detekce nádoru MeSH
- kolorektální nádory diagnóza MeSH
- mikro RNA analýza krev MeSH
- plošný screening MeSH
- sekundární prevence MeSH
- Konspekt
- Biochemie. Molekulární biologie. Biofyzika
- NLK Obory
- molekulární biologie, molekulární medicína
- gastroenterologie
- onkologie
- NLK Publikační typ
- závěrečné zprávy o řešení grantu IGA MZ ČR
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
- MeSH
- apoptóza MeSH
- buněčný cyklus MeSH
- kolorektální nádory * genetika MeSH
- lidé MeSH
- metastázy nádorů MeSH
- mikro RNA * diagnostické užití genetika MeSH
- patologická angiogeneze MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
BACKGROUND: Colorectal cancer (CRC) is one of the leading causes of cancer-related death in the world. Therefore, there is a high demand for cost-effective and non-invasive biomarkers that would enable an early detection of asymptomatic and curable disease with high sensitivity and specificity. OBJECTIVE: The main objective of this study was to investigate the potential of circulating miRNAs as biomarkers of CRC. METHODS: Total RNA enriched for small RNAs was isolated from 100~sera of patients with CRC and 30 sera of healthy donors. The expression levels of miR-17-3p, miR-29a, miR-92a and miR-135b were determined using quantitative real-time PCR. The average expression levels of particular miRNAs were normalized to miR-16 levels and statistically evaluated. RESULTS: Using Mann-Whitney U test, no significant differences were observed in miR-17-3p (P=0.18), miR-29a (P=0.14) and miR-92a (P=0.60) levels between sera of CRC patients and controls. The levels of miR-135b in serum were too low to be quantified accurately. Subsequently, we tried to correlate expression levels of analyzed miRNAs to clinical-pathological features of CRC patients. Only levels of mir-29a were correlated with the clinical stage (P=0.04). Expression levels of the other miRNAs were correlated neither with the clinical stage, nor with the grade. CONCLUSIONS: Interestingly, our results are contradictory to previous studies performed on the CRC patients from Chinese population, providing an evidence against usage of serum miR-17-3p, miR-29a, miR-92a and miR-135b as new biomarkers for early detection of CRC.
- MeSH
- dospělí MeSH
- kolorektální nádory krev diagnóza MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikro RNA krev MeSH
- nádorové biomarkery krev MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- studie případů a kontrol MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Publikační typ
- abstrakt z konference MeSH
