Exosomal circular RNA hsa_circ_0006220, and hsa_circ_0001666 as biomarkers in the diagnosis of pancreatic cancer

Abstract

Background Pancreatic cancer is a highly malignant tumor of the digestive system. Objective Exosomal circular RNA can be used as a biomarker for the early diagnosis of pancreatic cancer. Methods The expression of various differentially expressed circRNAs in pancreatic cancer tissues was analyzed by gene chip, exosome expression was verified by electron microscopy and Western blotting, and the expression of exosomal circRNA in pancreatic cancer cells, tissues, and plasma were determined by quantitative reverse transcription‐polymerase chain reaction (qRT‐PCR). Results Compared with healthy controls, hsa_circ_0006220 and hsa_circ_0001666 were highly expressed in exosomes in the plasma of pancreatic cancer patients. The AUC values were 0.7817 for hsa_circ_0006220, 0.8062 for hsa_circ_0001666, and 0.884 for the combined diagnosis. In addition, clinicopathological features revealed that the expression of hsa_circ_0006220 in plasma exosomes from pancreatic cancer patients was associated with CA19‐9 levels ( p = 0.0001) and lymph node metastasis ( p = 0.0005). The expression of hsa_circ_0001666 was correlated with both tumor size ( p = 0.0157) and CA19‐9 level ( p = 0.0001). Conclusions The high expression of exosomal hsa_circ_0001666 and hsa_circ_0006220 suggests that these can be used as new biomarkers for the diagnosis and treatment of pancreatic cancer.

Prognostic, Diagnostic, and Clinicopathological Significance of Circular RNAs in Pancreatic Cancer: A Systematic Review and Meta-Analysis

“…Another 149 studies were removed for not being related to PC or circRNAs, or not providing sufficient data. Ultimately, a total of 48 papers were included in our meta-analysis, including 34 on prognosis [ 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 ], 11 on diagnosis [ 29 , 30 , 31 , 48 , 55 , 56 , 60 , 61 , 62 , 63 , 64 ], and 30 on relationship with clinicopathological features [ 28 , 29 , 30 , 31 , 32 , 33 , 34 ,…”

“…In spite of this, circRNAs as biomarkers in PC still have the following advantages. First, some circRNAs, including hsa_circ_0004680 and hsa_circ_0001666, showed better discriminatory power in detecting PC patients from healthy controls, especially in PC with serum CA19-9 < 37 U/mL, suggesting that circRNAs might serve as a preferable biomarker for detecting PC [ 48 , 63 ]. Second, numerous reports have revealed the association between circRNA expression and chemotherapy resistance during PC treatment, implicating that the expression of circRNAs might have the potential to facilitate the selection of treatment options [ 92 , 93 ].…”

Clinical application and detection techniques of liquid biopsy in gastric cancer

“…For example, Li et al [ 229 ] found that using tRNA-GlyGCC-5 and sRESE alone has a much lower effect on identifying esophageal squamous cell carcinoma than using both. Hong et al [ 230 ] and Tang et al [ 231 ] found that the combination of exosome miRNAs or the combination of exosome miRNAs and CEA surpassed a single exosome miRNA marker in the diagnosis of GC. Our previous research found that the AUC value of GC diagnosis using circPTPN22 alone was 0.857, but the AUC value increased to 0.892 after combining traditional tumor markers CEA and CA199, demonstrating that the combined use of markers could compensate for the limitations of a single marker [ 146 ].…”

Roles of circular RNAs in the pathogenesis and treatment of pancreatic cancer

“…To date, five studies have reported the utility of serum circRNAs as diagnostic biomarkers for pancreatic cancer ( Table 2 ). That is, circLDLRAD3, circPDAC, hsa_circ_0013587, and circ_001569 were reported to be aberrantly expressed in the serum of pancreatic cancer patients ( Yang et al, 2017 ; Xu K. et al, 2021 ; Shen X. et al, 2021 ; Seimiya et al, 2021 ), and another study suggested that the combination of hsa_circ_0006220 and hsa_circ_0001666 can improve diagnostic performance compared with each circRNA alone ( Hong L. et al, 2022 ). These studies demonstrated that circRNAs have a sensitivity of 0.45–0.76 and specificity of 0.70–0.90 for diagnosis of pancreatic cancer.…”