Mountain View
biomedical and healthCAre Data Discovery Index Ecosystem
help Advanced Search
Title: MicroRNA Profiling Analysis of Differences between the Melanoma of Young Adults and Older Adults      
Transcriptome or Gene expression
This study represents the first attempt to perform a profiling analysis of the intergenerational differences in the microRNAs (miRNAs) of melanocytic neoplasms in young adult and older adult groups. Our comparative miRNA profiling provides a novel characterization of the miRnomes of melanocytic neoplasms and melanomas of different age groups and identifies a set of potential diagnostic and potential clinico-pathologic biomarkers that may serve as targets for development of novel miR-based modalities in cancer diagnosis and treatment. An exploratory miRNA analysis of 666 miRs was conducted on formalin fixed and paraffin embedded tissues from 10 adults and 10 young adults including conventional melanoma and melanocytic neoplasms of uncertain biological significance. Age-matched benign melanocytic nevi were used as controls. The comparative profiling was intentionally performed at two extremes of age, i.e., less than 30 years (Mel 30) and greater than 60 years (Mel 60). Primary melanoma in patients greater than 60 years old was characterized by the increased expression of miRs regulating TLR-MyD88-NF-kappaB pathway (hsa-miR -199a), RAS/RAB22A pathway (hsa-miR-204); growth differentiation and migration (hsa-miR337), epithelial mesenchymal transition EMT (let-7b, hsa-miR-10b/10bSTAR(*)), invasion and metastasis (hsa-miR-10b/10bSTAR(*), hsa-miR-30a/e*, hsa-miR-29c*; cellular matrix components (hsa-miR-29c*); invasion-cytokinesis (hsa-miR 99b*) compared to melanoma of younger patients. miR 211 was dramatically downregulated in primary melanoma compared to nevi controls, decreased with increasing age and was among the miRs linked to metastatic processes and potentially targeting the inflammatory receptor CCR10; Primary melanoma in young adult patients was characterized by the increased expression of hsa-miR-449a and decreased expression of hsa-miR146b, hsa-miR 214*. Among the miRs expressed at higher levels in control nevi, compared to adult or young adult melanoma, was hsa-miR 574-3p. Only 2 miRs distinguished adult from young adult-pediatric nevi, hsa-miR374a* and has-miR-566. MiR 30a* appeared to be a strong marker of differentiation in clinical stages I-II adult and pediatric melanoma, and could predict classification of melanoma tissue in the two age groups. Furthermore, lymph node status in the two age groups was characterized by the statistically significant expression of hsa-miR-30a* and hsa-miR-204 (F-test, p-value <0.001). Overall design: Archival paraffin blocks of melanocytic neoplasms studied at the University of Pittsburgh Cancer Institute (UPCI) were retrieved from the files of the Health Sciences Tissue Bank (HSTB) database and disbursed by UPCI HSTB according to UPCI-IRB regulations. Ten primary FFPE-tissues (including melanocytic neoplasms of uncertain biological potential) were obtained from two cohorts of patients respectively segregated according to age: Cohort A - > 60 years and Cohort B - <30 years and utilized for microRNA profiling. These two case cohorts were separated by at least 30 years, thereby representing an adequate basis for an intergenerational study. Additionally, 6 benign nevi were used as homologous controls (3 from adults and 3 from young adult patients, respectively). A total of 26 lesions (20 test specimens + 6 controls) were analyzed. Primary diagnostic workup and verification of the diagnosis of primary neoplasms was performed by two independent reference pathologists. Total RNA was isolated from all lesions from (at average) 30 5µm sections, and these were obtained specifically from areas that contained at least 70% viable tumor (identified by a pathologist). RNA quality was assessed using Nanodrop and the Agilent Bioanalyzer (OD 260/280 and 260/230 (Table 1)). The overall microRNA profiling of these two groups (adult and young adult) included a total of 56 Taqman ® microRNA Low density arrays (TLDAs). Each group included 10 melanocytic neoplasm samples (older adult melanoma, AM, pediatric and young adult melanoma PM) and 3 control nevi specimens (adult nevi, AN, pediatric nevi, PN). The assays were run in 3 batches for processing and a calibrator RNA was included in each batch for normalization. For each specimen, 2 TLDA were run, TLDA panel A and TLDA panel B.
Homo sapiens
National Center for Biotechnology Information
NCBI BioProject