MicroRNAs in Plasma of Pancreatic Ductal Adenocarcinoma Patients as Novel Blood-Based Biomarkers of Disease

Abstract

Development of minimally invasive biomarker assays for early detection and effective clinical management of pancreatic cancer is urgently needed to reduce high morbidity and mortality associated with this malignancy. We hypothesized that if aberrantly expressing microRNAs (miRNA) in pancreatic adenocarcinoma tissues are detected in blood plasma, then plasma profiling of these miRNAs might serve as a minimally invasive early detection biomarker assay for this malignancy. By using a modified protocol to isolate and quantify plasma miRNAs from heparin-treated blood, we show that miRNA profiling in plasma can differentiate pancreatic adenocarcinoma patients from healthy controls. We have profiled four miRNAs, miR-21, miR-210, miR-155, and miR-196a, all implicated in the development of pancreatic cancer with either proven or predicted target genes involved in critical cancerassociated cellular pathways. Of these, miR-155 has recently been identified as a candidate biomarker of early pancreatic neoplasia, whereas elevated expression of miR196a has been shown to parallel progression of disease. The results revealed a sensitivity of 64% and a specificity of 89% with the analyses of plasma levels for this panel of four miRNAs. The area under the receiver operating characteristic curve were estimated at 0.82 and 0.78 without and with leave-one-out cross-validation scheme, respectively. These observations, although a "proof of principle" finding at this time, show the feasibility of developing plasma miRNA profiling as a sensitive and specific blood-based biomarker assay for pancreatic cancer that has the potential of translation to the clinic with additional improvements in the future.

Plasma miR-200c and miR-18a as potential biomarkers for the detection of colorectal carcinoma

“…Additionally, the characteristics of miRNAs, such as tissue-specific miRNA signatures and the availability of numerous copies/cells, indicated potential advantages as biomarkers compared to those of other nucleic acids, such as circulating DNA and mRNA. An increasing number of studies also suggest the potential use of miRNAs in the early detection of patients with several malignancies, such as gastric, pancreatic, colorectal and breast cancer (6)(7)(8)(9). Recent studies have focused ons the role of circulating miRNAs in the plasma of CRC patients (7,18).…”

“…Mitchell et al (4) clearly demonstrated that circulating miRNAs originate from cancer tissues (4). Additional studies have demonstrated the presence of circulating miRNAs and their potential use as novel biomarkers of various types of cancer, such as pancreatic (6), colorectal (7), breast (8) and gastric cancers (9). These studies have provided new opportunities for a non-invasive examination for the early diagnosis of various types of cancer.…”

Epigenetic markers for chemosensitivity and chemoresistance in pancreatic cancer—A review

“…8,[58][59][60][61][62][63][64] Expression profiling has identified several miRNAs aberrantly expressed in PC cell lines and clinical tissue samples that were correlated with clinical outcome. [65][66][67][68][69][70][71][72][73][74] Alterations in miRNA expression profiles might be useful in the prediction of the individual response to chemotherapy and may even be targets for therapies to increase chemosensitivity.…”

Detection and quantification of extracellular microRNAs in medulloblastoma

“…Every cancer investigated has a distinct miRNA signature and deregulated levels of miRNAs have been detected in body fl uids of patients, including those with lymphoma, [11] leukemia, [12] colon, [13] breast, [14] prostate, [15] ovarian, [16] pancreatic, [17] gastric, [18] and lung cancer. [19] In the context of brain tumors, recent studies have demonstrated a signifi cant presence of certain miRNAs in CSF samples from patients with central nervous system lymphoma, glioma, and metastatic brain cancers.…”