Abstract
Aim: The high mortality rate of melanoma is due to partially the lack of good diagnostic markers and treatment strategies. Over the past several years, several microRNA (miRNA) profiling studies have been performed on melanoma tissues, but with extremely inconsistency, the diagnostic value of miRNA candidates in melanoma remains under debate. Thus, this study aims to systematically evaluate the consistency of miRNAs tissue in multiple independent studies in melanoma. Method: Eligible studies were screened and selected from the PubMed, EMBASE, and Web of Science. A systematic analysis of published miRNA expression studies that compared the miRNA expression profiles between melanoma tissues and normal skin tissue was conducted. A vote-counting strategy was followed with the collection of information. Real time PCRs were employed to validate miRNA candidates with high consistency. Targets of consistent miRNAs were predicted by online programs (like miRTarBase, microRNA.org and TargetScanHuman 6.2). Enrichment analyses for gene ontology (GO) terms and Kyoto encyclopedia of genes and genomes (KEGG) pathways were carried out with Database for Annotation, Visualization, and Integrated Discovery (DAVID). Results: A total of 303 differentially expressed miRNAs were reported in the 10 miRNA-profiling studies during comparison of melanoma tissues with normal tissues; 132 were up-regulated in melanoma, and 171 were down-regulated. However, in the group of consistently reported miRNAs (cutoff > 3 times), only moderate numbers of consistent and differentially expressed miRNAs were selected. miRNA-21 was found increased in 5 different studies, miRNA-146b, miRNA-17 and miRNA-18a were reported up-regulated in 4 profiling studies. Meanwhile, miRNA-204 and miRNA-125b were found down-regulated in 5 studies, miRNA-141, miRNA-149, miRNA-224, miRNA-200b, miRNA-200c were consistently decreased in just 4 out of 10 profiling studies in total. The directions of differential expression of these miRNA candidates were confirmed by real time PCRs. Enrichment analyses demonstrated that programmed cell death and transcription regulation played very important roles in the involvement of miRNAs in tumorigenesis of melanoma. Conclusion: This systematic study of melanoma miRNA profiling studies would provide rich information on miRNAs with potential role as the biomarkers and therapeutic agents with high consistency in melanoma.
Highlights
Cutaneous melanoma, as currently the sixth most common cancer in white men and women in the United States, is the most aggressive form of skin cancer characterized by poor prognosis [1], with the median no more than 1 year of survival time and is less than 5% of 5-year survival rate [2] [3]
A total of 68 studies were recorded using PubMed, EMBASE and web of science. 38 of which were excluded after screening the titles and abstracts, and 20 studies were excluded after reading the full text based on the inclusion and exclusion criteria, only 10 independent studies were included in this systematic analysis
These 10 studies from 10 different groups with different platforms, different number of samples, and various statistical analyses had been employed for microRNA profiling analysis to compare melanoma tissue with corresponding noncancerous skin tissue
Summary
As currently the sixth most common cancer in white men and women in the United States, is the most aggressive form of skin cancer characterized by poor prognosis [1], with the median no more than 1 year of survival time and is less than 5% of 5-year survival rate [2] [3]. Several studies have been conducted to search for biomarkers or therapeutic agents by identifying the differential expression of miRNAs between melanoma tissue samples and corresponding non-tumor skin tissue from the same patient [15]-[25]. These studies generated hundreds of differentially expressed miRNAs, many of these are likely to be false positives and only a small number of them may have clinical significance and act as diagnostic and prognostic biomarkers. It is crucial to identify skin tissue specific and consistently differentially expressed miRNAs to investigate the potential as biomarkers or therapeutic agents. Clarifying the molecular mechanisms of melanoma could provide a basis for melanoma risk assessment, early diagnosis, effective treatment and intervention
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