Leveraging different types of bodily fluids for cancer research

We developed a novel exosomal circRNA signature utilizing serum and biliary liquid biopsy methods. This innovative approach offers potential in identification of cholangiocarcinoma combined with biliary obstruction, and also monitors its recurrence following radical surgery.
Leveraging different types of bodily fluids for cancer research

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We are one of the few local laboratories that primarily focus on biliary diseases, located within Xinchuan Laboratory, West China Hospital, Sichuan University, in Chengdu, China. We are more than exited to share the stories behind the paper while also offering fresh insights into the related research field.

As a highly malignant biliary tract cancer, the diagnosis and prognosis assessment of cholangiocarcinoma (CCA) have long been challenging issues in clinical practice. In recent years, although there have been significant advancements in the clinical assessment of biliary tract cancer due to innovations in serological diagnostic methods and imaging techniques, their specificity and sensitivity still have limitations. Especially in patients with obstructive jaundice, CA 19-9 often presents false positive results, posing significant challenges to the clinical diagnosis of cholangiocarcinoma. Extracellular vesicles are nanosized particles secreted by cells, mediating intercellular communication and playing a crucial role in the development of diseases. In recent years, researchers have discovered various potential diagnostic biomarkers in extracellular vesicles in different hepato-pancreato-biliary  diseases, but practical diagnostic tools based on the "symptom-to-disease" pathway are still lacking. Therefore, this study utilizes circular RNA carried by extracellular vesicles in bile and serum as biomarkers, providing a new strategy for the diagnosis and early recurrence monitoring of CCA (see Figure.1).

Figure 1. Illustration on how this circRNA signature will possibly be applied under clinical settings.

It is noteworthy that this study innovatively analyzed two types of bodily fluid samples. By simultaneously analyzing patients' bile and serum samples, it revealed the applicability of biopsy strategies based on different bodily fluid samples. Particularly through this analytical strategy, the team found that bile may have a stronger correlation with the microenvironment of biliary diseases compared to serum. This further establishes the feasibility of bile samples as biomarkers for cholangiocarcinoma.

The idea to analyze two types of bodily fluids simultaneously stemmed from recognizing the potential advantages of each fluid in capturing different aspects of the disease process. We were intrigued by the notion that bile, being in direct contact with the biliary system affected by cholangiocarcinoma, might provide unique insights into the disease microenvironment. On the other hand, serum, being a more systemic fluid, could offer broader systemic markers of disease. By analyzing both fluids together, we aimed to uncover complementary information that could enhance our understanding of the disease and improve diagnostic accuracy.

We hope that our approach of simultaneously analyzing bile and serum samples in the context of cholangiocarcinoma research can serve as a beacon of inspiration for other researchers in the field. By shedding light on the unique diagnostic potential of these bodily fluids, we will be more than delighted to witness further exploration into innovative diagnostic strategies for not only cholangiocarcinoma but also other complex diseases.

Please feel free to contact Dr. Nansheng Cheng, corresponding author of this article, if you have any questions or comments about the work: nanshengcheng@yeah.net

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