Serum and Serum Exosomal CircRNAs hsa_circ_0001492, hsa_circ_0001439, and hsa_circ_0000896 as Diagnostic Biomarkers for Lung Adenocarcinoma

Abstract

BackgroundCircular RNAs (circRNAs) play an important role in tumorigenesis and several circulating circRNA signatures are closely associated with tumor diagnosis. However, the expression and clinical significance of the two forms of circulating circRNAs, serum and serum exosomal, in patients with lung adenocarcinoma (LUAD), have not been characterized.MethodsThree differentially expressed exosomal circRNAs, hsa_circ_0001492, hsa_circ_0001439, and hsa_circ_0000896, were selected based on previous exosomal circRNA sequencing data analyses of LUAD patients. The expression of these circRNAs in serum and serum-derived exosomes of LUAD patients was assessed using quantitative real-time PCR (qRT-PCR), and correlations between circRNA expression and clinicopathological characteristics were analyzed. The reliability of serum and serum exosomal hsa_circ_0001492, hsa_circ_0001439, and hsa_circ_0000896 to diagnose LUAD was evaluated using receiver operating characteristic (ROC) analysis.ResultsExpression of serum and serum exosomal hsa_circ_0001492, hsa_circ_0001439, and hsa_circ_0000896 were significantly higher in LUAD patients than in healthy donors, and significantly lower after surgery. These three serum exosomal circRNAs were also associated with a higher cancer stage. Exosomal hsa_circ_0001492 expression was positively correlated with carcinoembryonic antigen (CEA) and neuron-specific enolase (NSE) levels. An association between the expression of the three serum circRNAs and clinical characteristics was not observed. In addition, the three serum exosomal circRNAs had higher diagnostic sensitivity and specificity than the serum circRNAs, and the area under the curve (AUC) of all three serum exosomal circRNAs was >0.75. The combination of exosomal hsa_circ_0001492, hsa_circ_0001439, and hsa_circ_0000896 had better diagnostic sensitivity and specificity than that of a single marker, with an AUC value of 0.805.ConclusionsThe serum and serum exosomal circRNAs, hsa_circ_0001492, hsa_circ_0001439, and hsa_circ_0000896, were upregulated in LUAD patients. Serum exosomal circRNAs may serve as more effective biomarkers than serum circRNAs for LUAD diagnosis and may further aid the detection of this disease.

Hsa_circ_0041150 serves as a novel biomarker for monitoring chemotherapy resistance in small cell lung cancer patients treated with a first-line chemotherapy regimen

“…Hence, serum EV circRNAs demonstrated consistency with the rising trend observed in serum and proved to be more effective biomarkers than serum circRNAs. This is in line with the findings of Kang et al ( 2022 ), who reported that the diagnostic sensitivity and specificity of serum EV circRNAs were higher than those of serum circRNAs, suggesting the potential of serum EV circRNAs as a more effective biomarker for lung cancer.…”

Diagnostic value of exosomal noncoding RNA in lung cancer: a meta-analysis

“…Forty-one articles including 68 studies were included. Of these, 28 articles on microRNAs ( 16 – 43 ), comprising 45 studies; 8 articles on lncRNAs ( 44 – 51 ), comprising 9 studies; and 5 articles on circRNAs ( 52 – 56 ), comprising 14 studies. Diagnostic effect data included TP, FP, FN, TN, Sen, Spe, AUC, diagnostic likelihood ratio positive(DLR+), diagnostic likelihood ratio negative(DLR-), and diagnostic OR(DOR).…”

Tumor‐related exosomal circ_0001715 promotes lung adenocarcinoma cell proliferation and metastasis via enhancing M2 macrophage polarization by regulating triggering receptor expressed on myeloid cells‐2

“…Studies have reported that exosomes are rich in circRNAs, and exosomal circRNAs play a vital function in tumor biology 29 . In LUAD, Kang et al suggested that serum exosomal hsa_circ_0001492, hsa_circ_0001439, and hsa_circ_0000896 might act as the biomarkers for LUAD diagnosis 30 . Moreover, exosomal circRNA has been found to influence cancer progression by altering macrophage polarization, such as circ_0017252 31 and circFARSA 32 .…”

“… 29 In LUAD, Kang et al suggested that serum exosomal hsa_circ_0001492, hsa_circ_0001439, and hsa_circ_0000896 might act as the biomarkers for LUAD diagnosis. 30 Moreover, exosomal circRNA has been found to influence cancer progression by altering macrophage polarization, such as circ_0017252 31 and circFARSA. 32 In this, we detected high expression of circ_0001715 in the exosomes extracted from LUAD cells.…”