Validation of miR-1228-3p as Housekeeping for MicroRNA Analysis in Liquid Biopsies from Colorectal Cancer Patients

et al. 2021

Front. Oncol.

BackgroundDiagnosis of pancreatic cancer (Pca) is challenging. This study investigated the value of plasma-derived exosome miR-19b (Exo-miR-19b) in diagnosing patients with Pca.MethodsPlasma was collected from 62 patients with Pca, 30 patients with other pancreatic tumor (OPT), 23 patients with chronic pancreatitis (CP), and 53 healthy volunteers. MiR-19b levels in plasma-derived exosomes were detected.ResultsPlasma-derived Exo-miR-19b levels normalized using miR-1228 were significantly lower in Pca patients than in patients with OPT, CP patients, and healthy volunteers. The diagnostic values of Exo-miR-19b normalized using miR-1228 were superior to those of serum cancer antigen 19-9 (CA19-9) in differentiating Pca patients from healthy volunteers (area under the curve (AUC): 0.942 vs. 0.813, p = 0.0054), potentially better than those of CA19-9 in differentiating Pca patients from CP patients (AUC: 0.898 vs. 0.792, p = 0.0720), and equivalent to those of CA19-9 in differentiating Pca patients from patients with OPT (AUC: 0.810 vs. 0.793, p = 0.8206). When normalized using Caenorhabditis elegans miR-39 (cel-miR-39), Exo-miR-19b levels in Pca patients were significantly higher than those in patients with OPT, CP patients, and healthy volunteers. The diagnostic values of Exo-miR-19b normalized using cel-miR-39 were equivalent to those of CA19-9 in differentiating Pca patients from healthy volunteers (AUC: 0.781 vs. 0.813, p = 0.6118) and CP patients (AUC: 0.672 vs. 0.792, p = 0.1235), while they were inferior to those of CA19-9 in differentiating Pca patients from patients with OPT (AUC: 0.631 vs. 0.793, p = 0.0353).ConclusionPlasma-derived Exo-miR-19b is a promising diagnostic marker for Pca. The diagnostic value of plasma-derived Exo-miR-19b normalized using miR-1228 is superior to that of serum CA19-9 in differentiating patients with Pca from healthy volunteers.

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Plasma-Derived Exosome MiR-19b Acts as a Diagnostic Marker for Pancreatic Cancer

et al. 2021

Front. Oncol.

“…ERCC showed better performance in distinguishing healthy donors and HCC patients, so that we chose ERCC for further assays ( Figure S6 ). Based on previous studies 59 , we used miR-1228 rather than U6 snRNA as the internal reference for miRNAs to normalize the absolute cycle threshold (Ct) value in each sample.…”

Section: Methodsmentioning

confidence: 99%

Integrative analysis of long extracellular RNAs reveals a detection panel of noncoding RNAs for liver cancer

Zhu

et al. 2021

Theranostics

Rationale: Long extracellular RNAs (exRNAs) in plasma can be profiled by new sequencing technologies, even with low abundance. However, cancer-related exRNAs and their variations remain understudied. Methods: We investigated different variations (i.e. differential expression, alternative splicing, alternative polyadenylation, and differential editing) in diverse long exRNA species (e.g. long noncoding RNAs and circular RNAs) using 79 plasma exosomal RNA-seq (exoRNA-seq) datasets of multiple cancer types. We then integrated 53 exoRNA-seq datasets and 65 self-profiled cell-free RNA-seq (cfRNA-seq) datasets to identify recurrent variations in liver cancer patients. We further combined TCGA tissue RNA-seq datasets and validated biomarker candidates by RT-qPCR in an individual cohort of more than 100 plasma samples. Finally, we used machine learning models to identify a signature of 3 noncoding RNAs for the detection of liver cancer. Results: We found that different types of RNA variations identified from exoRNA-seq data were enriched in pathways related to tumorigenesis and metastasis, immune, and metabolism, suggesting that cancer signals can be detected from long exRNAs. Subsequently, we identified more than 100 recurrent variations in plasma from liver cancer patients by integrating exoRNA-seq and cfRNA-seq datasets. From these datasets, 5 significantly up-regulated long exRNAs were confirmed by TCGA data and validated by RT-qPCR in an independent cohort. When using machine learning models to combine two of these validated circular and structured RNAs ( SNORD3B-1, circ-0080695 ) with a miRNA ( miR-122 ) as a panel to classify liver cancer patients from healthy donors, the average AUROC of the cross-validation was 89.4%. The selected 3-RNA panel successfully detected 79.2% AFP-negative samples and 77.1% early-stage liver cancer samples in the testing and validation sets. Conclusions: Our study revealed that different types of RNA variations related to cancer can be detected in plasma and identified a 3-RNA detection panel for liver cancer, especially for AFP-negative and early-stage patients.

“…Colorectal cancer (CRC) is the third leading cause of cancer death in the world, and miRNA played an important role in the promotion or inhibition of apoptosis in CRC [ 7 ]. Duran-Sanchon et al [ 8 ] validated the previously suggested miR-1228-3p as an adequate endogenous control for circulating miRNA analysis in CRC by comparing its suitability with the widely used miR-16-5p, and they also evaluated the influence of hemolysis on both miRNAs. Human papillomavirus (HPV) infects millions of people each year, but the majority of individuals infected with HPV do not exhibit any clinical symptoms.…”

mentioning

confidence: 99%

microRNA Biomarkers in Clinical Study

Chen

2021

Biomolecules