Bile

Bile RNA — a window into biliary tract health

Bile is a yellowish-green fluid produced by the liver and stored in the gallbladder, playing a crucial role in the digestion and absorption of fats in the small intestine. Beyond its biological function, bile serves as a valuable diagnostic medium, as it contains secreted biomolecules reflective of the biliary environment.

RNA-sequencing of bile provides a powerful tool to uncover RNA biomarkers, offering insights into the molecular landscape of the biliary tract. This approach is particularly promising for detecting biliary tract cancers, which often have a poor prognosis due to late-stage diagnosis. Identifying RNA-based biomarkers in bile could pave the way for earlier diagnosis, improved prognostic tools, and personalized treatment strategies, transforming the management of these challenging diseases.

Why sequence bile with omiics

As with all cell-free biofluids, bile has ultra-low RNA content which makes detection difficult and requires expert sample preparation and bioinformatics. Omiics has optimized protocols for both total RNA-seq and small RNA-seq of bile, allowing detection of a large proportion of genes with good read depth using samples with an RNA content as low as 100 pg (total RNA) or 2 ng (small RNA).

The omiics team has ample expertise working with exosomes/extracellular vesicles, and we can reliably perform sequencing of both whole biofluid and EV/exosome purification fractions. Adding EV purification increases the difficulty of the RNA-seq, but it also significantly improves the quality of the output.

Image/figure for bile?

Total RNA

mRNA

lncRNA

circRNA

Small RNAs

miRNA, tRNA fragments (tiRNA), siRNA, piRNA

Case: Profiling biofluid RNA to uncover potential cancer biomarkers

Pancreatic Ductal Adenocarcinoma (PDAC) is an aggressive form of cancer, which has a 5-year survival rate of less than 5%, largely due to symptoms often not appearing until the later stages of disease progression, where surgical resection of the tumor is no longer possible. Symptoms of PDAC are often vague and do not specifically point to cancer, further complicating diagnosis.

Efficient screening of biofluid biomarkers could significantly improve early diagnosis, potentially allowing a greater number of patients to receive curative treatment through surgical resection.

Challenge:

Identify miRNA biomarkers of PDAC in blood plasma and bile liquid biopsies

Benefits:

+ Small RNA-seq of plasma and bile

+ Analysis of whole biofluids and extracellular vesicle (EV) fraction

+ Differential expression analysis of patients vs healthy subjects

Results:

A specific signature of significantly upregulated miRNA families was detected in extracellular vesicles in both plasma and bile

Read the full-length publication here

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