Randomized Controlled Trial
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 14, 2017; 23(34): 6330-6338
Published online Sep 14, 2017. doi: 10.3748/wjg.v23.i34.6330
Circular RNA hsa_circ_0000745 may serve as a diagnostic marker for gastric cancer
Mei Huang, Yi-Ren He, Li-Chuan Liang, Qiang Huang, Zhi-Qiang Zhu
Mei Huang, Qiang Huang, Anhui Province Key Laboratory of Hepatopancreatobiliary Surgery, Department of General Surgery, Anhui Provincial Hospital Affiliated to Anhui Medical University, Hefei 230001, Anhui Province, China
Yi-Ren He, Li-Chuan Liang, Qiang Huang, Zhi-Qiang Zhu, Department of General Surgery, Anhui Provincial Hospital Affiliated to Anhui Medical University, Hefei 230001, Anhui Province, China
Author contributions: Zhu ZQ conceptualized and designed the study; Huang M carried out the analysis and drafted the manuscript; He YR reviewed the statistics; Liang LC and Huang Q contributed to the literature search, data interpretation, and critical revisions; all authors reviewed and approved the final manuscript as submitted.
Supported by National Natural Science Foundation of China, No. 81501354.
Institutional review board statement: The study was reviewed and approved by the Anhui Provincial Hospital Institutional Review Board.
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: All authors declare that no competing interests exist.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Dr. Zhi-Qiang Zhu, Department of General Surgery, Anhui Provincial Hospital Affiliated to Anhui Medical University, No. 17, Lujiang Road, Hefei 230001, Anhui Province, China. zhuzhiqiang@ahmu.edu.cn
Telephone: +86-551-62283840 Fax: +86-551-62283666
Received: April 9, 2017
Peer-review started: April 10, 2017
First decision: May 12, 2017
Revised: June 7, 2017
Accepted: July 12, 2017
Article in press: July 12, 2017
Published online: September 14, 2017
Abstract
AIM

To determine whether circular RNAs (circRNAs) are involved in pathological processes of gastric cancer (GC).

METHODS

Three circRNAs with differential expression in GC and colorectal cancer were randomly selected for validation by quantitative reverse transcription-polymerase chain reaction (qRT-PCR), using 20 pairs of gastric tissues and normal tissues. Based on the predicted circRNA-miRNA network, we then focused on hsa_circ_0000745, which was found to be down-regulated in 20 GC tissues compared with normal tissues. The hsa_circ_0000745 levels were further analyzed by qRT-PCR in 60 GC tissues and paired adjacent non-tumor tissues, as well as 60 plasma samples from GC patients and 60 plasma samples from healthy controls. The associations between the levels of hsa_circ_0000745 and the clinicopathological features of GC patients were statistically assessed. A receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of hsa_circ_0000745 in GC.

RESULTS

Hsa_circ_0000745 was down-regulated in GC tissues vs non-tumorous tissues (P < 0.001) and in plasma samples from patients with GC vs healthy controls (P < 0.001). The expression level of hsa_circ_0000745 in GC tissues correlated with tumor differentiation, while the expression level in plasma correlated with tumor-node-metastasis stage. The area under the ROC curve (AUC) of hsa_circ_0000745 in plasma was 0.683, suggesting good diagnostic value. Plasma hsa_circ_0000745 level combined with carcinoembryogenic antigen (CEA) level increased the AUC to 0.775.

CONCLUSION

Hsa_circ_0000745 plays an important role in GC and its expression level in plasma in combination with CEA level is a promising diagnostic marker for this malignancy.

Keywords: Circular RNA, circ_0000745, Gastric cancer, Diagnosis, Noncoding RNA

Core tip: This study demonstrates that expression of hsa_circ_0000745 is down-regulated in human gastric cancer (GC), with significantly lower levels detected in human GC tissues compared to paired adjacent non-tumor tissues, and in plasma of GC patients compared to plasma from normal healthy controls. Detection of this stable circular RNA in plasma may represent a clinically useful and convenient marker for GC diagnosis, with higher sensitivity and specificity when analyzed in combination with carcinoembryogenic antigen.