Five circRNAs Serve as Potential Diagnostic and Prognostic Biomarkers in Lung Adenocarcinoma

Abstract

Background: The mortality rate of lung adenocarcinoma ranks first worldwide, higher than gastric, colorectal, breast, and other cancers. The lack of effective and accurate diagnosis contributes to the patient's unfavorable prognosis with lung adenocarcinoma since most patients are diagnosed at a late stage. In the present study, we aimed to investigate five circRNAs correlated with lung adenocarcinoma and their clinical roles.

Methods: We collected 68 unpaired serum and tissue samples from patients with lung adenocarcinoma and healthy volunteers. At the next stage, quantitative real-time polymerase chain reaction (qRT-PCR) assays were conducted. Furthermore, we uncovered the correlation of their expressions with clinicopathological features and the diagnostic values. Finally, the 5-year survival rate and disease-free rate were analyzed using Kaplan-Meier methods.

Results: The results revealed that expression levels of hsa_circ_001010, hsa_circ-ZNF609 were significantly elevated while hsa_circ-CRIMI1, hsa_circ-EPB41L2, and hsa_circ_0072309 were lower in lung adenocarcinoma serum samples and tissues than those in healthy controls (p < 0.05). Meanwhile, hsa_circ_001010 and hsa_circ-ZNF609 were downregulated hsa_circ-CRIMI1, hsa_circ-EPB41L2, and hsa_circ_0072309 were elevated in A549 cells compared with BEAS-2B cells. Knockdown of hsa_circ-CRIMI1, hsa_circ-EPB41L2, or hsa_circ_0072309 and overexpressing of hsa_circ_001010 and hsa_circ-ZNF609 could promote A549 cell apoptosis but inhibits proliferation as well. Furthermore, receiver operating characteristic (ROC) assays demonstrated that the area under the curve (AUC) were as follows: hsa_circ_001010 (0.8512, 95% CI, 0.7872 - 0.9152; p < 0.0001), hsa_circ-ZNF609 (0.7876, 95% CI, 0.7101 - 0.8651; p < 0.0001), hsa_circ-CRIMI1 (0.6614, 95% CI, 0.5708 - 0.7521; p < 0.0001), hsa_circ-EPB41L2 (0.6851, 95% CI, 0.5960 - 0.7742; p = 0.0002), and hsa_circ_0072309 (0.7359, 95% CI, 0.6250 - 0.8199; p < 0.0001). Notably, higher expressions of hsa_circ_001010, hsa_circ-ZNF609, and lower expressions of hsa_circ-CRIMI1, hsa_circ-BGT2, hsa_circ-EPB41L2, and hsa_circ_0072309 were positively correlated with clin-ical stage, lymph node metastasis, and smoking. Last but not least, patients with higher expressions of hsa_ circ_001010, hsa_circ-ZNF609, and lower expressions of hsa_circ-CRIMI1, hsa_circ-EPB41L2, and hsa_circ_ 0072309 had significantly lower overall survival rates and disease-free rates as well.

Conclusions: We concluded that the five circRNAs might have diagnostic and prognosis significance in lung ade-nocarcinoma. However, further functional studies are warranted to ascertain the biological mechanisms of these circRNAs in the occurrence and development of lung adenocarcinoma.