Exosome-derived circRNAs in early detection of pancreatic cancer

Pancreatic cancer, ranked as the ۱۲th most common cancer among ۲۷ types, is often asymptomatic in its early stages, and no methods exist for diagnosing early-stage cancers. Early detection of pancreatic cancer is crucial for improving therapeutic strategies. Current diagnostic methods often fail to detect the disease at an early stage, leading to poor survival rates. Targeting specific microRNAs (miRNAs) or circular RNAs (circRNAs) involved in cancer progression could lead to the development of novel therapies. Exosomes play a crucial role in intercellular communication and regulation of the tumor microenvironment in pancreatic cancer. They are involved in various key processes, including metastasis, cell proliferation, epithelial-mesenchymal transition (EMT), angiogenesis, and the tumor microenvironment (TME). Exosomes are considered valuable biomarkers for the diagnosis of pancreatic cancer in the beginning stages. Previous studies have highlighted certain mutations in exosomal proteins, such as KRAS and TP۵۳ in tumor tissues. Moreover, CA-۱۹-۹ antigen, another protein biomarker, can be useful in symptomatic patients to confirm a diagnosis and predict prognosis and recurrence after resection. Other studies have identified specific miRNAs, such as miR-۲۱ and miR-۲۱۰, as potential biomarkers for pancreatic cancer. Combining multiple miRNA biomarkers has shown promising results, with a reported accuracy of ۹۰%. However, due to less sensitivity and specificity, they are insufficient as screening tools for patients without any particular symptoms. Circular RNAs (circRNAs) are a type of non-coding RNA with a unique circular structure. Their stability and cancer-associated functions make them attractive candidates for biomarkers. Furthermore, they have a high half-life and are more highly expressed in cancer tissue than in normal tissue. For example, circ_IARS has been associated with the suppression of miR-۱۲۲, leading to cell migration and invasion in pancreatic cancer. Other investigations suggest that circ-has-۰۰۰۱۶۶۶, circ-has-۰۰۰۶۲۲۰, and circ-has-۰۰۷۱۰۳۶, found in the exosomes of pancreatic cancer (PC) patients, are highly expressed compared to adjacent tissues and play a special role in tumor development and metastasis. Moreover, circ-BFAR and circ-ASH۲L are associated with lymph node metastasis, and circ-LDLRAD۳ causes tumor cell invasion, proliferation, and migration through the miR-۱۳۷-۳P/PNT axis. These findings demonstrate that biomarkers such as circRNAs can not only aid in early detection but also provide important insights for therapeutic intervention. This study investigates the potential of molecular biomarkers, especially exosomal circRNAs, as promising tools for early detection and improving therapeutic strategies for pancreatic cancer.

کلیدواژه ها:

Pancreatic cancer ، exosome ، circRNA ، early detection