Prognostic value of microRNA expression levels in pancreatic adenocarcinoma: a review of the literature

Abstract

BackgroundClinical and pathologic markers of prognosis and patterns of failure help guide clinicians in selecting patients for adjuvant therapy after surgical resection for pancreatic adenocarcinoma (PDAC). Recent studies have reported the prognostic utility of microRNA profiling in numerous malignancies. Here, we review and summarize the current literature regarding associations between microRNA expression and overall survival in PDAC patients.Materials and MethodsWe conducted a systematic search in the PubMed database to identify all primary research studies reporting prognostic associations between tumor and/or serum microRNA expression and overall survival in PDAC patients. Eligible articles were reviewed by the authors and relevant findings are summarized below.ResultsWe found 53 publications that fit our search criteria. In total, 23 up-regulated and 49 down-regulated miRNAs have been associated with worse overall survival. MiR-21 is the most commonly reported miRNA, appearing in 19 publications, all of which report aberrant over-expression and association with shorter survival in PDAC. Other miRNAs that appear in multiple publications include miR-10b, −21, −34a, −155, −196a, −198, −200c, −203, −210, −218, −222, and −328. We summarize the preclinical and clinical data implicating these miRNAs in various molecular signaling pathways and cellular functions.ConclusionsThere is growing evidence that miRNA expression profiles have the potential to provide tumor-specific prognostic information to assist clinicians in more appropriately selecting patients for adjuvant therapy. These molecules are often aberrantly expressed and exhibit oncogenic and/or tumor suppressor functions in PDAC. Additional efforts to develop prognostic and predictive molecular signatures, and further elucidate miRNA mechanisms of action, are warranted.

Expression of selected MicroRNAs in pancreatic ductal adenocarcinoma in relation to tumor progression and patient’s outcome.

“…There is growing evidence that miRNA expression profiles have a potential to provide tumor-specific prognostic information. Several recent works have reported associations between microRNA expression and overall survival in PDAC patients [22,57,63,64]. In our study we observed no correlation between expression of all selected miRNAs and OS or PFS (Tables 8 and 9).…”

Tumor-Secreted Exosomal miR-222 Promotes Tumor Progression via Regulating P27 Expression and Re-Localization in Pancreatic Cancer

“…In PDAC, similar to other tumors, the majority of tumor-related miRNAs are tumor suppressors; for example, the miR-200 family was found to be downregulated and play important roles in EMT, cell proliferation and apoptosis [34]. Other tumor suppressors include miR-26, miR-34a, and miR-192 [35]. Oncogenic miRNAs are relatively scarce.…”

Targeting EphA2 with miR-124 mediates Erlotinib resistance in K-RAS mutated pancreatic cancer

“…Accumulating evidence has indicated that the dysregulation of miRNA was a frequent event in many cancer types, including PC . MiRNA has recently been shown to mediate resistance to anticancer agents in PC.…”

“…Accumulating evidence has indicated that the dysregulation of miRNA was a frequent event in many cancer types, including PC. [23] MiRNA has recently been shown to mediate resistance to anticancer agents in PC. For instance, miRNA-210 was down-regulated in gemcitabine-resistant PC cells, and miRNA-210 overexpression enhanced the sensitivity of PC cells to gemcitabine.…”