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Cancer Epidemiol Biomarkers Prev. 2018 Oct 30. pii: cebp.0723.2018. doi: 10.1158/1055-9965.EPI-18-0723. [Epub ahead of print]

Circulating plasma microRNAs as potential biomarkers of non-small cell lung cancer obtained by high-throughput real-time PCR profiling.

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College of Life Sciences and Oceanography, Shenzhen University.
State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center.
Shenzhen University Health Sciences Center, Shenzhen University.
Department of Thoracic Surgery, Peking University Shenzhen Hospital.
The Second Clinical Medical College (Shenzhen People's Hospital).
College of Life Sciences and Oceanography, Shenzhen University



Because of limited stability and sensitivity, circulating miRNAs as noninvasive biomarkers has not so far been used for early diagnosis and prognosis of non-small cell lung cancer (NSCLC) in clinic. Therefore, it is still imperative to find more reliable biomarker(s).


We performed one of most sensitive RT-qPCR assays, S-Poly(T) Plus to selected differently expressed miRNAs from genome-wide miRNA profiling. miRNA candidates were validated through a three-phase selection and two-validation process with 437 NSCLC cases and 415 controls.


A unique set of 7 and 9 miRNAs differed significantly in adenocarcinoma (ADC) and squamous cell carcinoma (SCC) samples compared with those in controls, of which, there were 5 universal biomarkers for NSCLC (ADC or SCC). Ten out of eleven miRNAs could discriminate early stage (Stage I) of NSCLC from healthy individuals. Risk score was obtained from the validation set-1 and was tested using operating characteristic (ROC) curves with a high area under ROC curve of 0.89 in ADC and 0.96 in SCC. Ultimately, potential biomarkers and the risk score were verified by the validation set-2 with a sensitivity of 94% and a specificity of 91.6% in ADC, and a sensitivity of 98.5% and a specificity of 51.5% in SCC, respectively.


Taken together, 7 miRNAs and 9 miRNAs may provide noninvasive biomarkers for diagnosis and prognosis in ADC and SCC, respectively.


Based on our sensitive and accurate method, we hope that these candidate miRNAs may have strong impact on the early lung cancer diagnosis.

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