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. 2017 Oct;14(4):4605-4612.
doi: 10.3892/ol.2017.6819. Epub 2017 Aug 24.

Abnormal alterations of miR-1 and miR-214 are associated with clinicopathological features and prognosis of patients with PDAC

Qing Cheng  1 , Li-Hua Han  1 , Hai-Juan Zhao  1 , Hui Li  1 , Jian-Bing Li  1
Affiliations

Abnormal alterations of miR-1 and miR-214 are associated with clinicopathological features and prognosis of patients with PDAC

Qing Cheng et al. Oncol Lett. 2017 Oct.

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a devastating malignant disease with a poor prognosis. PDAC is known to be difficult to diagnose at an early stage and to exhibit poor recurrence-free prognosis, but there is also a lack of effective treatment and limited knowledge of its biological characteristics. Therefore, there is an urgent requirement for an improved understanding of the cellular or molecular properties associated with PDAC, and to explore novel avenues for the diagnosis and treatment of this disease. In the present study, the microRNA (miRNA/miR) profiles of sera and tumor samples from patients with PDAC and healthy controls were investigated by miRNA microarray, and the potential role of miR-1 expression in PDAC was determined. A total of 43 patients attending the clinic diagnosed with PDAC at Changzhi City People's Hospital were invited to participate. Blood and surgical tumor samples were obtained for analysis by miRNA microarray and the reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The surgical tumor tissue was additionally used to determine miRNAs status by in situ hybridization (ISH). The results of microarray revealed that: i) 27 miRNAs in the sera and 23 miRNAs in the tumor tissues obtained from patients with PDAC were different compared with their matched controls; ii) miR-1, miR-10b and miR-214 were significantly altered in the PDAC group, either in the sera or tumor tissue samples. Results from the RT-qPCR, which detected the levels of miRNAs in patients with PDAC, confirmed those obtained from the miRNA microarray. In particular, the results of the present study revealed that decreased miR-1 and increased miR-214 in the PDAC tissues were associated with the clinicopathological features and survival rates of patients with PDAC. The results of the present study indicated that miRNAs serve an important role in PDAC carcinogenic progression and supplied useful markers, including miR-1, miR-214 and miR-10b, for determining PDAC prognosis using noninvasive methods.

Keywords: clinicopathological features; microRNA-1; microRNA-10b; microRNA-214; pancreatic ductal adenocarcinoma; survival rate.

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Figures

Figure 1.
Figure 1.
miRNA analysis of sera and tumor samples between PDAC and healthy controls. The heat-map identifiesthe significant differentially expressed miRNAs. miRNA expression in paired sera of patients with PDAC with healthy controls and tumor tissuesfrom patients with PDAC with the adjacent normal tissues were profiled. Red and green colors represent high and low expression, respectively. (A) Sera. (B) Tumor. miR, microRNA; PDAC, pancreatic ductal adenocarcinoma; hsa, Homo sapiens.
Figure 2.
Figure 2.
Differential miRNAs between PDAC and control samples. (A) Sera samples. (B) Tumor samples. The diagram demonstrates that among the differential miRNAs between the pancreatic ductal adenocarcinoma and control groups, miR-1, miR-10b and miR-214 were different either in the sera or in the tumor tissue samples. miR, microRNA; PDAC, pancreatic ductal adenocarcinoma.
Figure 3.
Figure 3.
miRNA expression as detected using RT-qPCR. Expression levels of (A) miR-1, (B) miR-10b and (C) miR-214 in sera and tumor samples from patients with PDAC and controls were estimated by RT-qPCR. Results are presented as the mean ± standard error of the mean. *P<0.05 vs. control. RT-qPCR, reverse transcription-quantitative polymerase chain reaction; miR, microRNA; PDAC, pancreatic ductal adenocarcinoma.
Figure 4.
Figure 4.
ISH positive staining of miR-1, miR-10b and miR-214 in PDAC and normal adjacent tissues. (A) ISH staining of miR-1 in normal tissue. (B) ISH staining of miR-10b innormal tissue. (C) ISH staining of miR-214 in normal tissue. (D) ISH staining of miR-1 in PDAC tissue. (E) ISH staining of miR-10b in PDAC tissue. (F) ISH staining of miR-214 in PDAC tissue. ISH signaling for miR-1 was observed to be weak in PDAC tissues, but marked in normal adjacent tissues. There was marked positive staining for miR-10b and miR-214 in PDAC tissues compared with that in normal adjacent tissues. Magnification, ×400. ISH, in situ hybridization; miR, microRNA; PDAC, pancreatic ductal adenocarcinoma.
Figure 5.
Figure 5.
Survival curves (5-year) of patients with PDAC with miR-1 and miR-214 ISH status. (A) Patients with PDAC who were negative for miR-1, as determined by ISH, demonstrated significantly poorer 5-year survival compared with those with positive ISH results (*P<0.05 vs. miR-1 positive samples). (B) Patients with miR-214-positive ISH signaling exhibited significantly poorer survival compared with those with negative ISH signaling (*P<0.05 vs. miR-214 negative samples). ISH, in situ hybridization; miR, microRNA; PDAC, pancreatic ductal adenocarcinoma.
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