The combination of circulating long noncoding RNAs AK001058, INHBA-AS1, MIR4435-2HG, and CEBPA-AS1 fragments in plasma serve as diagnostic markers for gastric cancer
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Dong Ke1,2,3, Hanwei Li2, Yi Zhang2,3, Yinghong An4, Hanjiang Fu2, Xuedong Fang1,3, Xiaofei Zheng2
1General Surgery, The Second Hospital of Jilin University, Changchun, 130041, China
2Beijing Key Laboratory for Radiobiology, Beijing institute of Radiation Medicine, Beijing, 100850, China
3Gastrointestinal Colorectal and Anal Surgery, The China-Japan Union Hospital of Jilin University, Changchun, 130033, China
4Clinical Laboratory Center, Chinese PLA Air Force General Hospital, Beijing, 100142, China
Hanjiang Fu, email: [email protected]
Xuedong Fang, email: [email protected]
Xiaofei Zheng, email: [email protected]
Keywords: gastric cancer, long noncoding RNA, plasma, biomarker, RNA fragments
Received: November 30, 2016 Accepted: February 14, 2017 Published: February 22, 2017
Background: Suitable diagnostic markers for cancers are urgently required in clinical practice. Long non-coding RNAs, which have been reported in many cancer types, are a potential new class of biomarkers for tumor diagnosis.
Results: Five lncRNAs, including AK001058, INHBA-AS1, MIR4435-2HG, UCA1 and CEBPA-AS1 were validated to be increased in gastric cancer tissues. Furthermore, we found that plasma level of these five lncRNAs were significantly higher in gastric cancer patients compared with normal controls. By receiver operating characteristic analysis, we found that the combination of plasma lncRNAs with the area under the curve up to 0.921, including AK001058, INHBA-AS1, MIR4435-2HG, and CEBPA-AS1, is a better indicator of gastric cancer than their individual levels or other lncRNA combinations. Simultaneously, we found that the expression levels of a series of MIR4435-2HG fragments are different in gastric cancer plasma samples, but most of them higher than that in healthy control plasma samples.
Materials and Methods: LncRNA gene expression profiles were analyzed in two pairs of human gastric cancer and adjacent non-tumor tissues by microarray analysis. Nine gastric cancer-associated lncRNAs were selected and assessed by quantitative real-time polymerase chain reaction in gastric tissues, and 5 of them were further analyzed in gastric cancer patients’ plasma.
Conclusions: Our results demonstrate that certain lncRNAs, such as AK001058, INHBA-AS1, MIR4435-2HG, and CEBPA-AS1, are enriched in human gastric cancer tissues and significantly elevated in the plasma of patients with gastric cancer. These findings indicate that the combination of these four lncRNAs might be used as diagnostic or prognostic markers for gastric cancer patients.
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