Upregulation of circRNA_0000285 serves as a prognostic biomarker for nasopharyngeal carcinoma and is involved in radiosensitivity

Abstract

Despite significant medical advancement, nasopharyngeal carcinoma (NPC) remains one of the most difficult types of cancer to detect and treat. Circular RNA (circRNA) signatures may be used as prognostic and predictive factors for cancer. Previous studies indicated that the biological role of circular homeodomain interacting protein kinase 3 (HIPK3) has cancer type-specificity. The HIPK3 gene locus formats three circRNA isoforms: circRNA_100783, circRNA_0000285 and circRNA_100782. However, their roles in NPC remain unknown. In the present study, whether these circRNAs could be used as a biomarker for NPC diagnosis and predicting treatment response was investigated. Reverse transcription-quantitative polymerase chain reaction was performed to measure the levels of circRNA_100783, circRNA_0000285 and circRNA_100782 in NPC and adjacent tissues. In addition, the circRNA_0000285 levels were further confirmed in serum samples from patients with NPC and healthy controls. The results demonstrated that circRNA_0000285, but not circRNA_100782 and circRNA_100783, was significantly increased in NPC tissues and serum samples from patients with NPC, compared with adjacent tissues and serum samples from healthy controls, respectively. Furthermore, circRNA_0000285 expression was increased in patients with radioresistant NPC, compared with patients with radiosensitive NPC. Further analysis demonstrated that circRNA_0000285 was significantly associated with tumor size (P<0.001), differentiation (P=0.022), lymph node metastasis (P=0.035), distant metastasis (P=0.022) and Tumor-Node-Metastasis stage (P<0.001). Additionally, univariate and multivariate analyses indicated that circRNA_0000285 may be an independent prognostic factor for the outcome of patients with NPC. The present data indicated that circRNA_0000285 may be a novel biomarker for NPC and is involved in NPC radiosensitivity.

Keywords: biomarker; circRNA_0000285; circular RNA; circular homeodomain interacting protein kinase 3; nasopharyngeal carcinoma; radiosensitivity.

Figure 1.

The circRNAs expression in NPC and adjacent tissues. Reverse transcription-quantitative polymerase chain reaction was performed to measure the expression of (A) circRNA_0000285, (B) circRNA_100783 and (C) circRNA_100782 in NPC (n=150) and adjacent tissues (n=100). circRNA, circular RNA; NPC, nasopharyngeal carcinoma.

Figure 2.

The expression of circRNA_0000285 in NPC cancer cells. Reverse transcription-quantitative polymerase chain reaction was performed to measure the expression of circRNA_0000285 in four NPC cancer cell lines and the normal nasopharyngal epithelial NP69 cell line. *P<0.05 vs. NP69. circRNA, circular RNA; NPC, nasopharyngeal carcinoma.

Figure 3.

The expression of circRNA_0000285 in serum samples. (A) Reverse transcription-quantitative polymerase chain reaction was performed to measure the expression of circRNA_0000285 in serum samples of patients with NPC (n=150) and healthy patients (n=100). (B) The expression of circRNA_0000285 in serum samples of patients with radiosensitive NPC (n=80) and radioresistant NPC (n=45). (C) The Kaplan-Meier survival curve depicts the survival rate in patients with high (n=105) or low circRNA_000285 expression (n=45). circRNA, circular RNA; NPC, nasopharyngeal carcinoma.