Identification of Differentially Expressed miRNAs in Appendiceal Mucinous Cystadenocarcinoma from Mucinous Cystadenoma.

Richard Licheng Wu,Shadan Ali

doi:10.4172/1948-5956.1000371

Abstract

ObjectiveMucinous cystadenocarcinoma of appendix is a rare entity. Differentiating mucinous cystadenocarcinoma from mucinous cystadenoma is very challenging and depends on establishing the presence of malignant cells in the appendix wall. The invasion may be very difficult to assess in some cases, especially in early stages of the disease, which could have devastating prognostic effects on patients. Therefore, it is necessary to develop an ancillary test that can differentiate the mucinous cystadenocarcinoma from mucinous cystadenoma. So far, there is no report available about the role of differentially expressed miRNAs in the diagnosis of appendiceal mucinous cystadenocarcinoma.Materials and MethodsSix confirmed mucinous appendiceal cystadenocarcinoma and twelve mucinous appendiceal cystadenoma cases were selected. The total RNAs were extracted from the formalin-fixed paraffin-embedded specimen of these cases. The comprehensive miRNA microarray expression profiling from pooled aliquots of RNA samples from these two entities were analyzed to detect the differentially expressed miRNAs in mucinous cystadenocarcinoma. The best seven differentially expressed miRNAs were validated in individual cases by quantitative reverse transcriptase PCR (qRT-PCR).ResultsThe microarray miRNA expression profiling analysis revealed 646 miRNAs that were differentially expressed in the mucinous cystadenocarcinoma. Among these differentially expressed miRNAs, the expression of 80 miRNAs showed statistical difference (p<0.01). The quantitative RT-PCR validated that the expression of miR-1, miR-4328 was significantly down regulated in mucinous cystadenocarcinoma compared to the mucinous cystadenoma (p<0.05). On the other hand, the expression of miR-200b, miR-200c, miR-451, miR-223 and miR-21 were significantly upregulated in mucinous cystadenocarcinoma (p<0.05).ConclusionThe expression levels of miRNAs tested were significantly altered in the appendiceal mucinous cystadenocarcinoma samples compared to the mucinous cystadenoma. These data suggest that the miRNA expression in mucinous appendiceal neoplasm may help to supplement the morphological evaluation in distinguishing benign from malignant tumors.

Highlights

Mucinous cystadenocarcinoma of appendix is a very rare entity, which comprises only 4%-6% appendix neoplasm [1]
The microarray miRNA expression profiling analysis revealed 646 miRNAs that were differentially expressed in the mucinous cystadenocarcinoma
The quantitative RT-PCR validated that the expression of miR-1, miR-4328 was significantly down regulated in mucinous cystadenocarcinoma compared to the mucinous cystadenoma (p

Summary

Introduction

Mucinous cystadenocarcinoma of appendix is a very rare entity, which comprises only 4%-6% appendix neoplasm [1]. The diagnosis of mucinous cystadenocarcinoma is mainly based on the presence of invasive foci, angiolymphatic invasion or perineural invasion. The diagnosis of appendiceal mucinous cystadenocarcinoma could be very challenging and in some cases it may be very difficult to differentiate it from its benign counterpart mucinous cystadenoma. This is due to the difficulty in assessing the invasion, especially in early stages, and the lack, in some case, of overt cytological atypia. It is important to develop an ancillary test that could assist in differentiating the mucinous cystadenocarcinoma from mucinous cystadenoma of the appendix, in early stage. MicroRNAs (miRNAs) have drawn more attention from oncologists due to its critical roles in the oncogenesis as well as tumor diagnosis and prognosis

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Results

Conclusion