Hsa_circ_0006006 is a potential biomarker for prognosis and cisplatin resistance in non-small cell lung cancer.

Abstract

Background and objective: Platinum-based drugs, such as cisplatin (DDP), are the standard treatment, yet drug resistance has become a key challenge. Previous studies have shown that hsa_circ_0006006 promotes non small cell lung cancer (NSCLC) progression. This study aimed to reveal the role of specific circRNAs in DDP resistance in NSCLC and their potential clinical applications.

Methods: CircRNA sequencing data of three NSCLC tissue and three normal tissue samples were extracted from the GEO database based on conditions that matched the microarray expression profiles of circRNAs from human NSCLC lung samples and matched neighboring samples and raw matrix data and platform annotation data, and differential expression analysis was performed using the R language. Log2 Fold change > 1 and P < 0.05 were labeled as differential genes. Serum samples were collected from 31 NSCLC patients and 21 DDP-resistant NSCLC patients. The Kaplan-Meier method was used to detect the correlation between circRNA levels and survival prognosis of NSCLC patients. The relationship between circRNAs and clinicopathological characteristics of patients was assessed by chi-square test. RT-qPCR was performed to detect the expression of key circRNAs associated with DDP drug resistance. circRNAs were analyzed by ROC curves to assess the diagnostic potential. A549 cells and A549/DDP cells were cultured to verify the effect of up- and down-regulation of hsa_circ_0006006 on DDP drug resistance in NSCLC cells using colony formation assay and flow cytometry.

Results: Abnormally elevated hsa_circ_0006006 expression was closely associated with NSCLC survival prognosis as well as DDP resistance (p < 0.05) with good diagnostic efficacy (AUC for NSCLC = 0.91, p < 0.01; AUC for DDP resistant = 0.80, p = 0.00). This was further validated in the analysis of clinical samples (p < 0.05). Knockdown of hsa_circ_0006006 significantly reduced DDP resistance in NSCLC cells, while overexpression of hsa_circ_0006006 had the opposite effect (p < 0.05).

Conclusion: NSCLC survival prognosis is associated with aberrant expression of hsa_circ_0006006, which regulates NSCLC cell proliferation and apoptosis and thus promotes DDP drug resistance. These findings provide potential targets for patient prognosis and assessment of biomarkers of response to DDP therapies that can be used to aid in early diagnosis and prognostic assessment, as well as new options for the future development of relevant small-molecule inhibitors or nucleic acid drugs.