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Authors Yang YL, Chen K, Zhou YC, Hu ZX, Chen S, Huang YC
Received 30 September 2017
Accepted for publication 3 December 2017
Published 30 January 2018 Volume 2018:11 Pages 587—597
DOI https://doi.org/10.2147/OTT.S152957
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Lucy Goodman
Peer reviewer comments 2
Editor who approved publication: Prof. Dr. Geoffrey Pietersz
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.
Keywords: non-small-cell
lung cancer, microRNA, tumor markers, diagnosis, biomarker