Elsevier

Surgery

Volume 153, Issue 5, May 2013, Pages 663-672
Surgery

Original Communication
MicroRNA expression signatures in intraductal papillary mucinous neoplasm of the pancreas

https://doi.org/10.1016/j.surg.2012.11.016Get rights and content

Background

Intraductal papillary mucinous neoplasms (IPMN) represent a spectrum of tumors that range from low-grade (LG) dysplastic tumors to invasive cancer. Identification of IPMN at high risk for malignant transformation is important for the prevention and early treatment of pancreatic cancer. The roles of microRNA expression in the development of IPMN have not been extensively evaluated.

Methods

Expression patterns of 846 human microRNAs (miRNAs) was analyzed using microRNA microarray in 55 tissues, including LG IPMN (n = 10), moderate-grade (MG) IPMN (n = 5), high-grade (HG) IPMN (n = 5), invasive cancer with IPMN (IPMC; n = 10), pancreatic ductal adenocarcinoma without IPMN (PDA; n = 5), LG IPMN extracted from specimens that contain IPMC (LG_Ca; n = 10), and normal pancreatic tissues (n = 10).

Results

Fourteen miRNAs were differentially expressed in all IPMN tissues compared with normal pancreatic tissue. Expression level of 3 miRNAs was proportional to dysplasia level. Hierarchical clustering demonstrated grouping of 2 IPMN subgroups: LG and MG IPMN verses HG IPMN and IPMC. Expression of 15 miRNAs was significantly different between these groups. LG_Ca tissues clustered with the HG IPMC group, and 12 miRNAs were differentially expressed in LG_Ca, HG lesions, and IPMC compared with LG lesions. The expression patterns of selected miRNAs were validated using quantitative reverse-transcription real-time polymerase chain reaction. Hierarchical clustering demonstrated microRNA expression profile in IPMC was significantly different from PDA, suggesting that different pathways are involved in these cancer types.

Conclusion

This study demonstrates that miRNAs are involved in the development and progression of IPMN. We identified potential targets for diagnosis, prognostication, and treatment of IPMN.

Section snippets

Tissue samples

We used a prospective database of all patients identified as having IPMN in our institution between February 2002 and 2011. All of the tissues in our study were obtained from surgical resection specimens. A pathologist experienced in pancreatic pathology (E.B.) reviewed all histologic slides. After confirmation of a diagnosis of IPMN, the specimens were entered into the study. Histologic typing of the tumors was performed according to the classification recommended in the revised 2000 World

Differential miRNAs expression in IPMN tissues of the different grades compared with normal pancreatic tissues

We compared miRNA expression in LG, MG, HG, and invasive cancer arising in IPMN with that of normal pancreatic tissue. Fourteen differentially expressed miRNAs were found with P values <.05, and fold change cutoff 2, in all IPMN tissues compared with normal pancreas (Table I). All miRNAs were upregulated in disease tissues compared with normal pancreatic tissues. For 3 of these miRNAs (hsa-miR-10a_st, hsa-miR-146a_st, and hsa-miR-155_st), the ratio of miRNA expression in disease tissue compared

Discussion

During the past decade, a dramatic increase in the number of patients diagnosed with pancreatic cysts has been observed. Some of these lesions are benign and can be followed clinically; however, lesions such as IPMN and mucinous cystic neoplasms have the potential to progress to invasive pancreatic adenocarcinoma. These lesions, owing to their macroscopic cystic nature, enable early detection with radiologic examinations, and an opportunity for pancreatic cancer prevention. However, the lack of

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    This work was supported by the generous donation of the Enav Family Foundation for Pancreatic Cancer Research.

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