CircEHD2, CircNETO2 and CircEGLN3 as Diagnostic and Prognostic Biomarkers for Patients with Renal Cell Carcinoma

Abstract

Background: Circular RNA (circRNA) plays an important role in the carcinogenesis of various tumors. It is assumed that circRNAs have a high tissue and tumor specificity, thus they are discussed as cancer biomarkers. The knowledge about circRNAs in clear cell renal carcinoma (ccRCC) is limited so far, and thus we studied the expression profile of seven circRNAs (circCOL5A1, circEHD2, circEDEM2, circEGNL3, circNETO2, circSCARB1, circSOD2) in a cohort of ccRCC patients. Methods: Fresh-frozen normal and cancerous tissues were prospectively collected from patients with ccRCC undergoing partial/radical nephrectomy. Total RNA was isolated from 121 ccRCC and 91 normal renal tissues, and the circRNA expression profile was determined using quantitative real-time PCR. Results: circEHD2, circENGLN3, and circNETO2 were upregulated in ccRCC compared with non-malignant renal tissue. circENGLN3 expression was highly discriminative between normal and cancerous tissue. None of the circRNAs was correlated with clinicopathological parameters. High circEHD2 and low circNETO2 levels were an independent predictor of a shortened progression-free survival, cancer-specific survival, and overall survival in patients with ccRCC undergoing nephrectomy. Conclusions: The analysis of circRNAs may provide diagnostic and prognostic information. Thus, circRNAs could help to optimize the individual treatment and ultimately improve ccRCC patients’ survival.

Systematic Review With Meta-Analysis: Diagnostic, Prognostic and Clinicopathological Significance of CircRNA Expression in Renal Cancer

“…Overall, the risk of death in patients with high circRNA expression was 1.63 times higher than that in patients without high circRNA expression (95% CI =1.43-1.85). Interestingly, only Frey et al's study found that circNETO2 was highly expressed in RC, but prognostic analysis showed that circNETO2 may play a protective role in RC (16). No detailed experimental study has been conducted thus far, and determination of its mechanism may be a direction for the future development of targeted therapies.…”

“…For RC diagnosis, although there were only 4 studies addressed this topic, 7 indicators were revealed, providing a valid basis for the diagnosis of RC patients (16,27,30,37). Using SROC curve analysis, we calculated an AUC of 0.89 for circRNAs, indicating that 89% of our randomized RC patients had higher circRNA levels than the controls.…”

“…The results showed that circEGLN3, circEHD2, and circNETO2 may be used for the diagnosis of RC. Interestingly, high and low circEHD2 expression were also found to be independent predictors of the postoperative prognosis in patients with RC (16).…”

“…Of the 207 studies, we also excluded studies unrelated to RC or circRNAs, irrelevant records, reviews and other studies that did not meet the requirements of format and content, leaving 77 studies. After the analysis and evaluation of the remaining 77 studies, we found that some studies did not meet the inclusion criteria, and a total of 22 studies were actually available for reference after elimination (15,16,(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39). Among them, 18 were related to prognosis, 4 were related to diagnosis, and 12 were related to clinicopathology.…”

Ferroptosis Holds Novel Promise in Treatment of Cancer Mediated by Non-coding RNAs

“…There are several detecting methods (e.g., RT-qPCR, in situ hybridization, high-throughput sequencing) that are mature enough for circRNA profiles. CircRNAs are reported to abnormally express in many cancers, such as hepatocellular carcinoma (Aishanjiang et al, 2021), renal cell carcinoma (Frey et al, 2021), glioblastoma (Wei et al, 2021), and gastric cancer (Jiang et al, 2021). Recent studies show that circRNAs are able to reverse resistance to conventional therapeutic strategies in several cancers, such as circLIFR (Zhang et al, 2021b), ciRS-122 (Wang et al, 2020), and Cdr1as (Yuan et al, 2019) in chemoresistance and circATRNL1 in radioresistance.…”