The expression of miR-21 and miR-375 predict prognosis of esophageal cancer

doi:10.1016/j.bbrc.2014.03.087

Biochemical and Biophysical Research Communications

Volume 446, Issue 4, 18 April 2014, Pages 1197-1203

https://doi.org/10.1016/j.bbrc.2014.03.087 Get rights and content

Highlights

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Analysis the relationship between miRNA and the prognosis of EC.
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Found the expression of miR-21 and miR-375 can predict the prognosis of EC.
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High level of miR-21 has a negative impact on OS of EC.
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Low level of miR-375 has a negative impact on OS of EC.

Abstract

Background

MicroRNA is a class of small, well-conserved, non-coding RNAs, and could play a potential role as diagnostic and prognostic biomarkers of esophageal cancers. We aimed to review comprehensively the evidence of microRNA as prognostic biomarkers in esophageal cancers.

Methods

Studies were identified by searching PubMed, Embase and Web of Science until November 2013. Descriptive characteristics of studies were described and an additional meta-analysis for specific microRNAs which were studied most frequently was performed. Pooled hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) were calculated. Fixed model or random model method was chosen depending on the heterogeneity among the studies.

Results

Twenty-two studies including a total of 1946 participants were enrolled after a strict filtering and qualifying process. Among 33 prognostic microRNAs identified for esophageal cancer, miR-21 and miR-375 appeared more frequently. The median study size was 70.5 patients (29–249 patients) and the median HR was 3.305 (IQR = 1.615–7.31). For the studies evaluating miR-21’s association with overall survival (OS), the pooled HR suggested that high level of miR-21 has a negative impact on OS (HR = 1.52[1.17–1.98], P = 0.001). As for miR-375, the pooled HR for OS (high/low) was 0.53 (95% CI: 0.39–0.73, P < 0.001), indicated that low level of miR-375 has a negative impact on OS. These results indicated that microRNAs show promising associations with prognosis in esophageal cancer. Up-regulation of miR-21 and down-regulation of miR-375 can predict unfavourable prognosis in esophageal cancer.

Introduction

Esophageal cancer (EC) is the eighth most common cancer in the world and the sixth leading cause of cancer mortality [1]. Despite treatments have been improved recently the prognoses of part EC patients are still poor. How to determine the prognosis of EC patients is key role need to be solved.

Currently, investigators have focused on the potential of microRNAs (miRNAs) to serve as biomarkers for cancer. MiRNAs are small, endogenous, non-coding RNAs with 19–24 nucleotides in length. Aberrant expression of miRNAs in cancer tissue has been reported in various types of cancers, and increasing evidence suggested the potential of miRNA as prognostic markers in cancer.

Many articles have reported promising results for miRNA classifiers in EC prognosis. However, as a kind of biomarker, miRNA in EC patients remains largely unexplored. To clarify the effect of miRNAs as prognostic biomarkers, the data from the studies providing independent assessments of miRNAs in EC were systematically evaluated and synthesized. Furthermore, we performed the meta-analysis of two specific miRNAs (miR-21 and miR-375) as important prognostic classifiers for EC.

Section snippets

Search strategy, eligibility criteria and data extraction

A comprehensive literature search was done for original articles analyzing the prognostic value of miRNAs in EC with PubMed, Embase and Web of Science. Studies were selected by using the following keywords: esophagus, miRNA, cancer, prognosis. Original and review articles published until November 2013 were sought, considering the latter as an additional source of original works otherwise overlooked [2]. Additionally, the bibliographies reported in all the selected studies were reviewed to

Eligible studies

One hundred and sixty-one records for miRNA and were identified from a primary literature search in PubMed, EMBASE and web of science. After manually screening the titles, abstracts and keywords, 131 studies were excluded because they were review articles, letters, non-English articles, laboratory studies or studies irrelevant to the current analysis. And the remaining 30 studies were evaluated in full text. Of the 30 candidate studies, 6 studies lacked the key survival data, one study’s sample

Discussion

MiRNAs were proposed as promising biomarkers for early cancer detection and accurate prognosis as well as targets for more efficient treatment. Emerging studies have demonstrated that aberrant expression of miRNAs was associated with prognosis for EC. The results of their expression feature in cancer tissues or plasma (serum) are inconsistent and controversy still exists in identifying them as new biomarkers of EC prognosis. Therefore, systemically evaluate the most frequently reported miRNAs

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This investigation studied the impacts of the miR-30a-5p/CBX2 axis on esophageal cancer (EC).
Research objects were ascertained using The Cancer Genome Atlas database. Followed by qRT-PCR, western blot, dual-luciferase reporter, MTT, Transwell, and wound healing approaches, we tested gene expression and varying cell behaviors
Conspicuously miR-30 family members (miR-30a-5p, miR-30b-5p, miR-30c-5p, miR-30d-5p, miR-30e-5p) downregulation and CBX2 upregulation were discovered in EC cells. miR-30 family members target CBX2 and inhibited CBX2 expression. EC cell behaviors were inhibited by miR-30a-5p/CBX2 axis.
MiR-30a-5p draws a new inspiration for EC treatment.
Inhibition of miR-196a affects esophageal cancer cell growth in vitro
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Citation Excerpt :
Despite recent use of different therapeutic methods to treat EC, including surgery combined with radiotherapy or chemotherapy, the overall 5-year survival rate for EC patients remains quite low (10–40%) because of drug resistance and high systemic toxicity [6–8]. Several reports have indicated that abnormal accumulation or function of oncogenes or tumor suppressor genes are the main drivers of EC carcinogenesis and progression [9,10]. However, details of the underlying mechanism of EC development remain unclear.
Esophageal cancer (EC) is one of the most common causes of cancer-related mortality worldwide. Several oncogenes such as miR-196a have been implicated in the carcinogenesis and progression of EC. The purpose of this study was to determine the effects of anti-miR-196a on the growth and survival of human EC cells in vitro. We found that miR-196a was highly expressed in both TE1 and EC109 cells and that miR-196a knockdown inhibited cell proliferation and migration. Furthermore, miR-196a knockdown sensitized EC cells to radiation treatment and chemotherapy. Inhibition of miR-196a also altered cell cycle progression and induced G₂/M arrest, which was related to changes in the levels of cyclin B1. ABCG2, which was highly expressed in untransfected EC cells, was inhibited by miR-196a knockdown. Thus, our results confirm the fact that miR-196a is highly involved in the biological behavior of EC progression in vitro. We conclude that miR-196a is a useful biological marker and potential therapeutic target for the clinical treatment of human EC.
MicroRNA-21 and microRNA-375 from oral cytology as biomarkers for oral tongue cancer detection
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For tissue samples, the combination of miR-21 and miR-375 yielded an OOB prediction error rate of 5% (1/20). It is worth noting that the combination of miR-21 and miR-375 has been suggested as either diagnostic or prognostic biomarker in both laryngeal SCC [30–32] and esophageal cancers (both esophageal SCC and esophageal adenocarcinoma) [33–35] by multiple studies. Interestingly, the consistent up-regulation of miR-21 and down-regulation of miR-375 not only observed in cell-based samples (e.g., oral cytology and tissue samples), but also as circulating microRNAs [33,36,37].
We previously performed a meta-analysis of microRNA profiling studies on head and neck/oral cancer (HNOC), and identified 11 consistently dysregulated microRNAs in HNOC. Here, we evaluate the diagnostic values of these microRNAs in oral tongue squamous cell carcinoma (OTSCC) using oral cytology samples.
The levels of 11 microRNAs were assessed in 39 oral cytology samples (19 OTSCC and 20 normal subjects), and 10 paired OTSCC and adjacent normal tissues. The predictive power of these microRNAs was analyzed by receiver operating characteristic curve (ROC) and random forest (RF) model. A classification and regression trees (CART) model was generated using miR-21 and miR-375, and further validated using both independent oral cytology validation sample set (14 OTSCC and 11 normal subjects) and tissue validation sample set (12 paired OTSCC and adjacent normal tissues).
Differential expression of miR-21, miR-100, miR-125b and miR-375 was validated in oral cytology training sample set. Based on the RF model, the combination of miR-21 and miR-375 was selected which provide best prediction of OTSCC. A CART model was constructed using miR-21 and miR-375, and was tested in both oral cytology and tissue validation sample sets. A sensitivity of 100% and specificity of 64% was achieved in distinguishing OTSCC from normal in the oral cytology validation set, and a sensitivity of 83% and specificity of 83% was achieved in the tissue validation set.
The utility of microRNA from oral cytology samples as biomarkers for OTSCC detection is successfully demonstrated in this study.
MiR-328 suppresses the survival of esophageal cancer cells by targeting PLCE1
2016, Biochemical and Biophysical Research Communications
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Tanaka et al. found miR-27 to be associated with chemo-resistance in EC [15]. The regulation of miR-21 and miR-375 could predict the prognosis of EC [16]. MiR-21 expression was found to be elevated in EAC after neoadjuvant chemotherapy [17].
Esophageal cancer (EC) is the sixth leading cause of death worldwide. Recent studies have highlighted the vital role of microRNAs (miRNAs) in EC development and diagnosis. In our study, qPCR analysis showed that miRNA-328 was expressed at significantly low levels in EC109 and EC9706 cells. The results also showed that overexpression of miR-328 by lentivirus-mediated gene transfer markedly inhibited cell proliferation and invasion, and enhanced apoptosis; whereas, inhibition of miR-328 significantly promoted cell proliferation and invasion, and suppressed apoptosis in EC109 and EC9706 cells. Dual-luciferase reporter assay confirmed that miR-328 directly targeted phospholipase C epsilon 1 (PLCE1) by binding to target sequences in the 3′-UTR. qPCR and Western blot analysis showed that the PLCE1 was overexpressed in EC109 and EC9706 cells. Additionally, we found that miR-328 overexpression decreased PLCE1 mRNA and protein levels, while miR-328 inhibition enhanced the PLCE1 expression. Further analysis showed that PLCE1 overexpression rescued the inhibitory effect of miR-328 on cell proliferation and invasion, and repressed the promotive effect of miR-328 on cell apoptosis. In conclusion, our results suggest that miR-328 suppresses the survival of EC cells by regulating PLCE1 expression, which might be a potential therapeutic method for EC.
Epigenetic modifications in esophageal cancer: An evolving biomarker
2023, Frontiers in Genetics
Prognostic value of micro-RNA 375, 133, 143, 145 in esophageal carcinoma: A systematic review and meta-analysis
2022, Frontiers in Oncology

View all citing articles on Scopus

¹: These authors contribute to this work equally.

View full text

The expression of miR-21 and miR-375 predict prognosis of esophageal cancer

Highlights

Abstract

Background

Methods

Results

Introduction

Section snippets

Search strategy, eligibility criteria and data extraction

Eligible studies

Discussion

J. Biol. Chem.

Ann. Thorac. Surg.

FEBS Lett.

Cancer Lett.

Global cancer statistics, 2002

CA Cancer J. Clin.

The prognostic value of circulating tumor cells in patients with melanoma: a systematic review and meta-analysis

Clin. Cancer Res.

Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis of observational studies in epidemiology (MOOSE) group

JAMA

Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints

Stat. Med.

Aggregate data meta-analysis with time-to-event outcomes

Stat. Med.

Practical methods for incorporating summary time-to-event data into meta-analysis

Trials

Clinical outcome prediction by microRNAs in human cancer: a systematic review

J. Natl. Cancer Inst.

Bias in meta-analysis detected by a simple, graphical test

BMJ

Distinctive microRNA profiles relating to patient survival in esophageal squamous cell carcinoma

Cancer Res.

Overexpression of miR-200c induces chemoresistance in esophageal cancers mediated through activation of the Akt signaling pathway

Clin. Cancer Res.

miR-655 Is an EMT-suppressive microRNA targeting ZEB1 and TGFBR2

PLoS ONE

Prognostic significance of differentially expressed miRNAs in esophageal cancer

Int. J. Cancer

Prognostic impact of circulating miR-21 and miR-375 in plasma of patients with esophageal squamous cell carcinoma

Expert Opin. Biol. Ther.

MicroRNA-375 inhibits tumour growth and metastasis in oesophageal squamous cell carcinoma through repressing insulin-like growth factor 1 receptor

Gut

Overexpression of microRNA-223 regulates the ubiquitin ligase FBXW7 in oesophageal squamous cell carcinoma

Br. J. Cancer