Identification of circulating microRNA signatures as potential noninvasive biomarkers for prediction and prognosis of lymph node metastasis in gastric cancer.

Xiumei Jiang,Rui Wang,Lishui Wang,Chuanxin Wang,Weili Duan,Xiaoyun Yang,Lutao Du,Lili Wang,Yongmei Yang,Xin Zhang,Xiaoyang Chen,Wenfei Wang,Guixi Zheng

doi:10.18632/oncotarget.17789

Xiumei Jiang, Rui Wang + Show 11 more

Open Access

https://doi.org/10.18632/oncotarget.17789

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Abstract

Circulating microRNAs (miRNAs) are emerging as novel noninvasive biomarkers for prediction of lymph node metastasis (LNM) in cancer. The aim of this study was to identify serum miRNA signatures for prediction and prognosis of LNM in gastric cancer (GC). MiSeq sequencing was performed for an initial screening of serum miRNAs in 10 GC patients with LNM, 10 patients without LNM and 10 healthy controls. Reverse transcription quantitative real-time PCR was applied to confirm concentration of candidate miRNAs using a training cohort (n = 279) and a validation cohort (n = 180). We identified a four-miRNA panel (miR-501-3p, miR-143-3p, miR-451a, miR-146a) by multivariate logistic regression model that provided high predictive accuracy for LNM with an area under the receiver operating characteristic curve (AUC) of 0.891 (95% CI, 0.840 to 0.930) in training set. Prospective evaluation of this panel revealed an AUC of 0.822 (95% CI, 0.758 to 0.875, specificity = 87.78%, sensitivity = 63.33%) in validation set. Moreover, Kaplan–Meier analysis showed that LNM patients with low miR-451a and miR-146a levels had worse overall survival (OS) (p < 0.05). In Cox regression analysis, miR-451a was independently associated with OS of LNM (p = 0.028). Our results suggested that use of serum miRNAs seems promising in estimating the probability GC patients harbor LNM and providing prognostic information for LNM.

Highlights

Gastric cancer (GC) is the fourth most common malignancy and the second most frequent cause of cancerrelated death worldwide, with an estimated 951,600 new cases and 723,100 deaths in 2012 [1]
We investigated serum miRNA expression profiles by miSeq sequencing followed by independent validations in a large cohort, with the intention to identify a panel of circulating miRNAs for prediction of lymph node status in gastric cancer (GC)
Chang et al demonstrated that overexpression of miR-125b could promote cell migration and invasion in GC tissues by targeting STARD13 and NEU1 [19]

Summary

Introduction

Gastric cancer (GC) is the fourth most common malignancy and the second most frequent cause of cancerrelated death worldwide, with an estimated 951,600 new cases and 723,100 deaths in 2012 [1]. Presence of LNM is one of the most important prognostic factors and lymph node dissection has been proved to improve GC survival [5]. Preoperative determination of lymph node status is critical in providing guide on tumor staging and planning optimal treatment for GC. To date, imaging techniques such as computerized tomography, magnetic resonance imaging and positron emission tomography/computed tomography are commonly used for preoperative assessment of lymph node status. The measurement of lymph node size by these imaging techniques does not appear to be reliable indicator of LNM due to its limited accuracy [6, 7]. Www.impactjournals.com/oncotarget novel noninvasive biomarkers are urgently needed to complete and improve on current strategies for LNM prediction before surgery in GC

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