Summary Adenocarcinoma is the most common type of lung cancer, the leading cause of cancer deaths in the world. Early detection is the key to improve the survival of lung adenocarcinoma patients. We have previously shown that microRNAs were stably present in sputum and could be applied to diagnosis of lung cancer. The aim of this study was to develop a panel of microRNAs that can be used as highly sensitive and specific sputum markers for early detection of lung adenocarcinoma. This study contained three phases: (1) marker discovery using microRNA profiling on paired normal and tumor lung tissues from 20 patients with lung adenocarcinoma; (2) marker optimization by real-time RT-qPCR on sputum of a case-control cohort consisting of 36 cancer patients and 36 health individuals; and (3) validation on an independent set of 64 lung cancer patients and 58 cancer-free subjects. From the surgical tissues, seven microRNAs with significantly altered expression were identified, of which “four” were overexpressed and “three” were underexpressed in all 20 tumors. On the sputum samples of the case-control cohort, four (miR-21, miR-486, miR-375, and miR-200b) of the seven microRNAs were selected, which in combination produced the best prediction in distinguishing lung adenocarcinoma patients from normal subjects with 80.6% sensitivity and 91.7% specificity. Validation of the marker panel in the independent populations confirmed the sensitivity and specificity that provided a significant improvement over any single one alone. The sputum markers demonstrated the potential of translation to laboratory settings for improving the early detection of lung adenocarcinoma.

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Growing number of long noncoding RNAs (lncRNAs) are emerging as new modulators in cancer origination and progression. A lncRNA, ADAM metallopeptidase with thrombospondin type 1 motif, 9 (ADAMTS9) antisense RNA 2 (ADAMTS9-AS2), with unknown function, is the antisense transcript of tumor suppressor ADAMTS9. In the present study, we investigated the expression pattern and functional role of ADAMTS9-AS2 in glioma by using real-time PCR and gain-/loss-of-function studies. The results showed that the ADAMTS9-AS2 expression was significantly downregulated in tumor tissues compared with normal tissues and reversely associated with tumor grade and prognosis. Multivariate analysis of the prognosis factors showed that low ADAMTS9-AS2 expression was a significant independent predictor of poor survival in glioma. Overexpression of ADAMTS9-AS2 resulted in significant inhibition of cell migration in glioma, whereas knockdown of ADAMTS9-AS2 showed the opposite effect. We also found that ADAMTS9-AS2 expression was negatively correlated with DNA methyltransferase-1 (DNMT1). In addition, DNMT1 knockdown led to remarkable enhancement of ADAMTS9-AS2 expression. By 5-aza-dC treatment, the ADAMTS9-AS2 expression was also reactivated. The results suggested that ADAMTS9-AS2 is a novel tumor suppressor modulated by DNMT1 in glioma. LncRNA ADAMTS9-AS2 may serve as a potential biomarker and therapeutic target for glioma.