Application of serum microRNA-9-5p, 21-5p, and 223-3p combined with tumor markers in the diagnosis of non-small-cell lung cancer in Yunnan in southwestern China

Purpose: Xuanwei City is located in late Permian coal-accumulating areas of the northeastern region of Yunnan Province. In China, morbidity and mortality from lung cancer are highest in Yunnan. Identifying useful circulating markers suitable for the diagnosis of lung cancer in this region is quite meaningful. In this study, we evaluated diagnostic roles of serum miR-9-5p, 21-5p, 223-3p, 135b-5p, 339-5p, and 501-5p in patients with non-small-cell lung cancer (NSCLC) in Yunnan. Moreover, we evaluated the diagnostic performance of several tumor markers, including carcinoembryonic antigen (CEA), cytokeratin 19 fragment 21-1 (CYFRA21-1), and squamous cell carcinoma-related antigen (SCC). Methods: Quantitative real-time polymerase chain reaction detected six miRNAs in the serum of 104 NSCLC patients and 50 cancer-free controls. Other markers, including CEA, CYFRA21-1, and SCC, in serum were also measured. The diagnostic ability of miRNAs and tumor markers was evaluated by receiver operating characteristic (ROC) curve analysis. The diagnostic performance of these serum markers was also evaluated in Xuanwei and non-Xuanwei subjects, because the etiological and the epidemiological characteristics of lung cancer in Xuanwei were quite different from those in other regions. Results: Serum miR-9-5p, miR-21-5p, miR-223-3p, CEA, CYFRA21-1, and SCC were upregulated in NSCLC patients, compared with cancer-free controls. No significant difference was found in miR-135b-5p, miR-339-5p, and miR-501-5p expression. The area under ROC curves (AUCs) of miR-9-5p, miR-21-5p, miR-223-3p, CEA, CYFRA21-1, and SCC were 0.706, 0.765, 0.744, 0.749, 0.735, and 0.616, respectively. When combined, miRNAs and tumor markers yielded the highest diagnostic power, with AUC of 0.886, sensitivity of 82.69%, and specificity of 88.00%. In Xuanwei subjects, miR-223-3p and CEA may be suitable biomarkers to distinguish NSCLC from cancer-free states with AUCs of 0.752 and 0.791, respectively. The diagnostic power of the combination of miRNAs and tumor markers was still the highest in both subgroups (region: Xuanwei and non-Xuanwei; stages: I-II and III-IV). Conclusion: Serum miR-9-5p, miR-21-5p, miR-223-3p, CEA, CYFRA21-1, and SCC could be potential diagnostic biomarkers for NSCLC patients in Yunnan. miRNAs and tumor markers should be combined to diagnose NSCLC, as it showed better ability for screening patients with NSCLC.