Plasma microRNAs as biomarkers of pancreatic cancer risk in a prospective cohort study

Abstract

Non-invasive biomarkers for early pancreatic ductal adenocarcinoma (PDAC) diagnosis and disease risk stratification are greatly needed. We conducted a nested case-control study within the Prospective Investigation into Cancer and Nutrition (EPIC) cohort to evaluate pre-diagnostic microRNAs (miRs) as biomarkers of subsequent PDAC risk. A panel of eight miRs (miR-10a, -10b, -21-3p, -21-5p, -30c, -106b, -155, and -212) based on previous evidence from our group was evaluated in 225 microscopically confirmed PDAC cases and 225 controls matched on center, sex, fasting status, and age/date/time of blood collection. MiR levels in pre-diagnostic plasma samples were determined by quantitative RT-PCR. Logistic regression was used to model levels and PDAC risk, adjusting for covariates, and to estimate area under the receiver operating characteristic curves (AUC). Plasma miR-10b, -21-5p, -30c and -106b levels were significantly higher in cases diagnosed within 2 yr of blood collection compared to matched controls (all P-values <0.04). Based on adjusted logistic regression models, levels for six miRs (miR-10a, -10b, -21-5p, -30c, -155, and -212) overall, and for four miRs (-10a, -10b, -21-5p, and -30c) at shorter follow-up time between blood collection and diagnosis (≤5 yr, ≤2 yr), were statistically significantly associated with risk. A score based on the panel showed a linear dose-response trend with risk (P-value=0.0006). For shorter follow-up (≤5 yr), AUC for the score was 0.73, and for individual miRs ranged from 0.73 (miR-212) to 0.79 (miR-21-p).

Personalized RNA Medicine for Pancreatic Cancer

“…42, 43) and resistance to multiple anticancer agents (44) and is a promising noninvasive biomarker for pancreatic cancer risk and detection (24,45,46). As miR-21 is already a key detectable biomarker for PDAC (27,47,48), in a future phase I clinical trial, we propose to prospectively identify patients presenting with a similar miRNA signature that could be eligible for this biomarker-based RNA therapy.…”

Integrative Analysis of MicroRNA and Gene Interactions for Revealing Candidate Signatures in Prostate Cancer

“…It is well-established that a large number of specific miRNAs are involved in the carcinogenesis and development of tumors by regulating the expressions of their targeted mRNAs (Inui et al, 2010). With advancements in biological and clinical research, miRNA-mRNA interactions have been widely demonstrated to regulate the complicated molecular mechanisms underlying oncogenesis, development, invasion, and metastasis of tumors (Duell et al, 2017;Han et al, 2017). The Cancer Genome Atlas (TCGA) database has stored numerous genomic and gene expression profiles for various types of tumors.…”

Identification of four plasma microRNAs as potential biomarkers in the diagnosis of male lung squamous cell carcinoma patients in China

“… claimed that miR‐21‐5p mediated cellular proliferation, invasion, migration, and apoptosis by targeting PTEN, RECK, and Bcl‐2 in LSCC. At present, a robust association of miR‐21‐5p expression in tumors with diagnostic effect was also observed in numerous solid tumors, such as colorectal cancer , gastric cancer , breast cancer , pancreatic cancer , and so on. Moreover, overexpression of miR‐21‐5p was correlated with poor survival of the patients with pancreatic cancer and gastric cancer .…”