Correlations of hsa_circ_0046264 expression with onset, pathological stage and chemotherapy resistance of lung cancer

Z.-H. Liu, S.-Z. Yang, X.-T. Chen, M.-R. Shao, S.-Y. Dong, S.-Y. Zhou, L. Liu

Department of Thoracic Surgery, The First Affiliated Hospital of China Medical University, Shenyang, China. 148035452@qq.com

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• Oncology

OBJECTIVE: The purpose of this study was to investigate the correlations of hsa_circ_0046264 expression with the onset, pathological stage, and chemotherapy resistance of lung cancer.

PATIENTS AND METHODS: Firstly, gene expression profiling microarrays were applied to screen the differentially expressed circular ribonucleic acids (circRNAs) in the tumor tissues of patients with non-small cell lung cancer (NSCLC). Secondly, quantitative Reverse Transcription-Polymerase Chain Reaction (RT-qPCR) assay was adopted to further verify the circRNAs with significant differences. Thirdly, the correlations of hsa_circ_0046264 expression level with the clinical features of NSCLC patients were explored via statistical analysis. Fourthly, Kaplan-Meier survival analysis and receiver operating characteristic (ROC) curve were utilized to investigate the influence of hsa_circ_0046264 expression level on the survival of the patients. Finally, the role of hsa_circ_0046264 in the process of lung cancer was probed using in vitro experimental methods.

RESULTS: It was shown in the results of gene microarray assay that hsa_circ_0046264 was the most prominently upregulated gene, and RT-qPCR assay further proved that hsa_circ_0046264 expression was upregulated remarkably in the tissues of tumor patients. Clinical analysis indicated that the expression level of hsa_circ_0046264 was notably associated with the patient’s age, tumor size, tumor-node-metastasis (TNM) stage, and lymph node metastasis (p<0.01). In addition, Kaplan-Meier statistical analysis manifested that the patients in hsa_circ_0046264 low-expression group had a markedly longer survival than those in hsa_circ_0046264 high-expression group. In the tumor tissues and serum of the patients, the area under ROC curve of hsa_circ_0046264 was 0.971 and 0.915, the specificity was 0.973 and 0.957, and the sensitivity was 0.951 and 0.927, while the Youden Index was 0.924 and 0.884 respectively. The results of Cell Counting Kit-8 (CCK-8) assay revealed that the proliferative ability of lung cancer A549 cells was significantly enhanced at 36, 48, and 72 h in hsa_circ_0046264 overexpression group. According to the results of wound-healing assay, the migratory ability of A549 cells was distinctly strengthened in hsa_circ_0046264 overexpression group compared with that in the control group (p<0.05). Moreover, the transwell assay results pointed out that the invasive ability of A549 cell lines at 48 h after overexpression of hsa_circ_0046264 was evidently stronger than that in control group (p<0.05). Under the stimulation of different doses of cisplatin, hsa_circ_0046264 overexpression group had a clearly raised survival rate of A549 cells in comparison with control group, and the differences in data were statistically significant (p<0.01).

CONCLUSIONS: Hsa_circ_0046264 may serve as a potential biomarker for the diagnosis and prognosis and a possible therapeutic target of lung cancer.

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