Diagnostic and Prognostic Implications of a Serum miRNA Panel in Oesophageal Squamous Cell Carcinoma

Abstract

Background and AimCirculating microRNAs (miRNAs) are potential biomarkers for cancer detection; however, little is known about their prognostic impact on oesophageal squamous cell carcinoma (ESCC). The current study aims to uncover novel miRNAs for prognostic biomarkers in ESCC patients.Patients and MethodsWe initially screened the expression of 754 serum miRNAs using TaqMan Low Density Array in two pooled samples respectively from 28 ESCC and 28 normal controls. Markedly upregulated miRNAs in ESCC and some miRNAs reported to be differently expressed in ESCC tissue were then validated individually by RT-qPCR in another 83 patients and 83 controls arranged in two phases. The changes of the selected miRNAs during the esophagectomy and their prognostic value were examined.ResultsSeven serum miRNAs were found to be significantly higher in ESCC than in controls; namely, miR-25, miR-100, miR-193-3p, miR-194, miR-223, miR-337-5p and miR-483-5p (P<0.0001), and the area under the receiver-operating-characteristic (ROC) curve (AUC) for the seven-miRNA panel was 0.83 (95% CI 0.75–0.90). Most of these miRNAs declined markedly in postoperative samples versus preoperative samples (P<0.05). Moreover, high level of miR-25 was significantly correlated with shorter overall survival in patients (P = 0.027). Cox regression analysis identified lymph node metastasis, miR-25 and miR-100 as the independent risk factors for overall survival (hazard ratio (HR) 2.98 [1.36–6.55], P = 0.006; HR 3.84 [1.02–14.41], P = 0.029; HR 4.18 [1.21–14.50], P = 0.024, respectively).ConclusionThe seven serum miRNAs could potentially serve as novel biomarkers for ESCC; moreover, specific miRNAs such as miR-25 and miR-100 can predict poor survival in ESCC.

Prognostic value of microRNA-100 in esophageal squamous cell carcinoma

“…To the best of our knowledge, the recent studies on the role of miR-100 in ESCC have been controversial. In the present study of a relative large cohort, we confirmed that the expression levels of miR-100 in human ESCC tissues were markedly reduced when compared with matched normal esophageal tissues, which was consistent with the findings of Sun et al [14], but was different from the data of Ko MA et al [12] and Wu et al [13].…”

“…Growing evidence suggest that the aberrant expression of miR-100 is associated with tumorigenesis and tumor progression. Especially, Ko MA et al [12] observed the upregulation of miR-100 in ESCC tissues, which was consistent with the findings of Wu et al [13] in serum of ESCC patients. In contrast, Sun et al [14] showed the downregulation of miR-100 in 101 ESCC surgical tissue samples and in three ESCC cell lines.…”

Multiple Roles of MicroRNA-100 in Human Cancer and its Therapeutic Potential

“…The Solexa sequencing results from Zhang et al demonstrated marked upregulation of 25 serum miRNAs including miR-100 in ESCC patients compared with controls [29]. Similarly, together with the other six serum miRNAs, miR-100 was found to be significantly higher in ESCC than in controls [28]. From those above studies, it was concluded that miR-100 might be a more reliable diagnostic biomarker for human cancers as a result of its aberrant expression in tumorigenesis.…”

Circulating Cell-free miRNA Expression and its Association with Clinicopathologic Features in Inflammatory and Non-Inflammatory Breast Cancer

“…(Yan et al, 2008) miR-548d-5p Bladder Urine Expressed predominantly in patients with higher cancer stages (Brisuda et al,2014) miR-342-5p Ovarian Whole blood Decreased levels in ovarian cancer (Hausler et al, 2010) miR-15a Breast Serum Increased serum level in older compared to young breast patients (Kodahl et al, 2014) miR-342-3p Breast Serum High serum level in older compared to young breast patients (Hatse et al, 2014) miR-29a Colorectal Plasma Increased plasma levels in advanced-stage cancer than controls (Huang et al, 2010) miR-451 Breast Plasma Increased plasma level found in breast cancer patients (Van der Auwera et al, 2010) miR-30b Breast Serum high levels in the serum of breast cancer patients than control subjects (Hamdi et al,2014) miR-337-5p ESCC Serum Serum levels were differentially expressed between ESCC patients and controls (Wu et al, 2014) miR-486-3p…”