Circulating miR-17-3p, miR-29a, miR-92a and miR-135b in serum: Evidence against their usage as biomarkers in colorectal cancer

Faltejsková, Petra; Bočánek, Ondřej; Šachlová, Milana; Svoboda, Marek; Kiss, Igor; Vyzula, Rostislav; Slabý, Ondřej

doi:10.3233/cbm-130308

Cited by 47 publications

(44 citation statements)

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“…Our results support this finding, as we found elevated miR-17-3p levels in the serum of early-stage colon cancer patients. However, in 2013, Faltejskova et al reported that there was no significant difference in the serum levels of miR-17-3p between CRC patients and healthy controls (16). As we analyzed miR-17-3p expression using the same protocol as that used in the Faltejskova et al study, we also used miR-16 as control to evaluate the expression.…”

Section: Discussionmentioning

confidence: 99%

“…To evaluate the diagnostic value of miR-17-3p and CEA that were identified in previous studies (16,17), serum samples of 70 stage I/II colon cancer patients and 70 healthy controls were examined by radioimmunoassay and RT-qPCR, respectively. miR-16 was used as the endogenous control, as it displayed high stability, high abundance and low variability in analyzed serum samples.…”

Section: Serum Sample Examinationmentioning

confidence: 99%

“…Several studies have recently identified miRNAs expressed at different levels in the serum of cancer patients compared with healthy controls (9)(10)(11)(12). miRNAs have been suggested as potential reliable biomarkers for tumor screening (13,14) due to their extremely stable nature and the fact that they may be However, a later study found no significant differences between miR-17-3p levels in the serum of CRC patients and heathy controls (16). The aim of the present study was to investigate whether CEA and miR-17-3p are elevated in the serum of stage I̸II colon cancer patients and assess their potential as novel biomarkers for this type of cancer.…”

Section: Introductionmentioning

confidence: 99%

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Combined assays for serum carcinoembryonic antigen and microRNA-17-3p offer improved diagnostic potential for stage I/II colon cancer

Zhu

Dong

Zhang

et al. 2015

Molecular and Clinical Oncology

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Abstract. Colorectal cancer is among the leading causes of cancer-related mortality, one of the main reasons for which is the lack of an effective screening method for early-stage disease. The levels of carcinoembryonic antigen (CEA) and microRNA (miR)-17-3p in the serum of 70 patients with stage I̸II colon cancer and 70 healthy volunteers were determined, and the diagnostic value of CEA plus miR-17-3p detection for colon cancer was assessed. The levels of CEA were measured by a radioimmunoassay method, and those of miR-17-3p using the reverse transcription-quantitative polymerase chain reaction method. miR-16 was used as the endogenous control, as it displayed high stability, high abundance and low variability in the analyzed serum samples. The receiver operating characteristic (ROC) curve analysis indicated the potential diagnostic value of the two markers and the area under the ROC curve (AUC) for CEA and miR-17-3p was 0.719 (95% CI: 0.658-0.843) and 0.807 (95% CI: 0.748-0.906), respectively. At a threshold of 9.6 ng/ml for CEA, the optimal sensitivity and specificity were 74.6 and 84.3%, respectively, in discriminating colon cancer patients from healthy controls. At a threshold of 2.98 for miR-17-3p, the sensitivity and the specificity were 83.6 and 72.9%, respectively. A combined ROC analysis using CEA and miR-17-3p revealed an AUC of 0.929 (95% CI: 0.834-0.978) with a sensitivity of 96.4% and a specificity of 95.7% in discriminating colon cancer patients from healthy controls. In conclusion, both CEA and miR-17-3p were highly expressed in the serum of our series of colon cancer patients. CEA plus miR-17-3p detection significantly increased the sensitivity and specificity in discriminating stage I/II colon cancer patients from healthy controls. Therefore, combined detection of serum CEA and miR-17-3p levels may have the potential to become a new laboratory method for the early clinical diagnosis of colon cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Serum Sample Examinationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Combined assays for serum carcinoembryonic antigen and microRNA-17-3p offer improved diagnostic potential for stage I/II colon cancer

Zhu

Dong

Zhang

et al. 2015

Molecular and Clinical Oncology

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“…Tracing it to the cause of these conflicting conclusions of circulating miRNAs in diagnosis, early screening, TNM stage and prognosis, may be attributed to the following factors: (1) genetic variations among different region, ethnic groups and different environmental and dietary factors, (2) difference of sample collection procedures or processing conditions, the source choice of plasma, serum or whole blood (3) uniform inclusion and exclusion criteria of subjects (i.e., early or late stages of cancers) to the same research purpose (diagnosis or TNM stage), (4) usage of pooled samples, (5) different internal controls including miR-16, RNU6B or cel-miR-39, and variety ways of data normalization and analysis in the quantification of RNA levels with qRT-PCR, (6) different miRNA expression levels between tissue and plasma, (7) sample size, screening method, and so on [51][52][53][54][55][56].…”

Section: Discussionmentioning

confidence: 99%

Circulating MicroRNAs in Colorectal Cancer

Huang¹,

Ge²,

Hu³

et al. 2017

J Mol Genet Med

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IntroductionWith increasing incidence, colorectal cancer (CRC) remains the second most common cancer in women and the third in men, despite the improved screening techniques, most patients diagnosed CRC are at late stage, CRC is the second leading cause of cancer-related death worldwide [1]. Complete tumor resection by surgery is the main therapeutic modality, it was reported that 5-year survival rates were in range from 93.2% for the earliest stage to 6.6% for advanced disease at diagnosis according to Duke's stage. So, good prognosis of CRC is linked to stage at earlier diagnosis. However, due to asymptomatic in early stage of CRC, many cases were detected at late stage. In clinical practice, colonoscopy is used in the diagnosis and treatment of CRC, but has not yet been wide-used as a screening tool because of some limitations, such as the requirements of bowel preparation, cost burden and perforation risk [2]. In addition, fecal occult blood test (FOBT), some convenient circulating blood biomarkers, including the most frequently used marker carcinoembryonic antigen (CEA), carbohydrate antigens, CA125, CA153 and CA199, are lack of sufficient sensitivity or specificity. For example, the specificity of FOBT is about 95%, while the sensitivity of is around 70% to 75% [3], the sensitivity and specificity of CEA is 60% and 34%, respectively [4]. Therefore, new strategies and novel biomarkers with the characters of detection, staging and prediction of outcome are highly desirable and being explored in order to make optimized treatment prescription and to improve prognosis for CRC patients.A growing number of researches focus on small non-coding RNA molecules, microRNAs (miRNAs, miRs), which play multiple roles in variety of biological processes, including cancer [5][6][7]. Since 2008, tumor-derived miRNAs were described present stablely in circulating blood, as circulating-based markers for cancer detection [8]. Consider the detection of circulating miRNAs have the advantages of simple, inexpensive and noninvasive, combined with the remarkable stability characteristics of mature miRNAs due to the miRNA-Argonaute-protein complex, the discovery of circulating miRNAs as novel biomarkers for cancer intervention has been widely explored [9,10]. Growing evidences have indicated that aberrant expression of circulating miRNAs has an association with cancer including CRC. The diagnostic and prognostic value of circulating miRNAs exhibited in screening and monitoring, predicting recurrence or metastasis including lymph node, vessel, peritoneal invasion or distant metastasis, stratification by TNM stage or even histological differentiation grade, and few are associated with drug resistance, chemoradiosensitivity, tumor size and gender. This review covers recent researches in circulating miRNAs and their variety potential values correlated with CRC (Figure 1). Experiment FlowExperiment flow for the identification of CRC-related circulating miRNAs apply step-wise strategy. First experiment samples are selected according to dif...

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“…In addition, miR-17-3p induces carcinoma by targeting vimentin (47), mediates stress responses by targeting MDM2 (48), and inhibits angiogenesis by downregulating fetal liver kinase-1 (49). In certain clinical studies, circulating miR-17-3p in serum has been indicated to be a potential non-invasive biomarker for colorectal cancer screening (50,51). Other studies have shown that the miR-17-92 cluster, which encodes miR-17-3p (and 6 other miRNAs), is expressed in numerous mammalian tissues, and this cluster contributes to the development of the heart, lungs, blood vessels and the immune system (52,53).…”

Section: Discussionmentioning

confidence: 99%

The effects of perfluorocarbon on ICAM-1 expression in LPS-induced A549 cells and the potential mechanism

Cao

Chang

et al. 2016

Mol Med Report

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Abstract. Acute lung injury (ALI)/ARDS is a critical clinical syndrome with high mortality, and the effective therapeutic methods for the treatment remain limited. Previous studies have indicated that liquid ventilation with perfluorocarbon (PFC) may be advantageous over conventional mechanical ventilation in the treatment of ALI/ARDS. Additionally, PFC inhibits the inflammatory response caused by ALI/ARDS. However, the anti-inflammatory mechanism remains to be completely elucidated. In the present study, the aim was to determine the anti-inflammatory mechanism of PFC and the association with microRNA (miR). PFC was used to modulate LPS-induced A549 cells, with the cells divided into four groups: Untreated control group; LPS group, treated with 10 µg/ml LPS; LPS+PFC group, treated with 10 µg/ml LPS and PFC; and PFC group, treated with PFC alone. The intercellular adhesion molecule-1 (ICAM-1) mRNA and protein expression levels of each group were detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting, respectively. A549 cells were transfected with miR-17-3p mimics, miR-17-3p inhibitors or negative controls to observe the alterations in the anti-inflammatory effects of PFC. A dual luciferase reporter gene assay was used to determine whether ICAM-1 is a target gene of miR-17-3p. PFC was observed to attenuate the mRNA and protein expression levels of ICAM-1 in LPS-induced A549 cells, with no significant effect on the untreated A549 cells. miR-17-3p was demonstrated to be regulated by PFC. Transfection with miR-17-3p mimics enhanced the anti-inflammatory effects of PFC, whereas the miR-17-3p inhibitor weakened the anti-inflammatory effects of PFC at early time points. To conclude, the current study indicates that ICAM-1 was a target gene of miR-17-3p, and PFC has anti-inflammatory effects. Additionally, the present study is the first report, to the best of our knowledge, that PFC is able to attenuate ICAM-1 expression in LPS-induced A549 cells by increasing miR-17-3p expression.

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Circulating miR-17-3p, miR-29a, miR-92a and miR-135b in serum: Evidence against their usage as biomarkers in colorectal cancer

Abstract: 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.

Cited by 47 publications

References 0 publications

Combined assays for serum carcinoembryonic antigen and microRNA-17-3p offer improved diagnostic potential for stage I/II colon cancer

Combined assays for serum carcinoembryonic antigen and microRNA-17-3p offer improved diagnostic potential for stage I/II colon cancer

Circulating MicroRNAs in Colorectal Cancer

The effects of perfluorocarbon on ICAM-1 expression in LPS-induced A549 cells and the potential mechanism

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