Identification Of Gastric Cancer Related Circular RNA Hsa_circ₀006633 And Its Clinical Significance

ObjectiveGastric cancer?GC?is one of the commonest malignant tumors,and is the third leading cause of cancer deaths in the world nowadays.The pathophysiology mechanism of gastric cancer is still not clear,patients are often found in the advanced stage,whose prognosis is poor.While the 5-year survival rate can reach more than 90 % after the medical measures if detected in the early stage of GC.CircRNAs are identified as one kind of RNAs that form covalently closed-loop structure by jointing 5? and 3? ends together.CircRNA is a class of biomolecule with important regulatory functions,which is closely related to the occurrence,development,invasion,metastasis of the tumor and prognosis of patients.As the role of circRNAs in GC remains unknown,it is very important to identify the circRNA molecules associated with GC.Here we chose hsa_circ₀006633 as the target circular RNA on the basis of previous studies,and measured its expression levels in human gastric cell lines,tissues,and plasma samples.Then its relationships with clinicopathological features,prognosis of patients were analyzed as well to clarify the clinical significance of hsa_circ₀006633 in the occurrence of GC.Methods?1?To measure the expression levels of hsa_circ₀006633 in normal gastric epithelial cell line?GES-1?and 4 gastric cancer cell lines?HGC-27?SGC-7901?MGC-803?AGS?by real-time quantitative reverse transcription polymerase chain reaction?qRT-PCR?.?2?Then the expression levels of hsa_circ₀006633 in GC tissues and their adjacent normal tissues were measured by qRT-PCR,and a receiver operating characteristic?ROC?curve was established to evaluate the sensitivity and specificity of hsa_circ₀006633 in the diagnosis of GC.?3?To detect and analyze hsa_circ₀006633 expression levels in healthy human gastric mucosa,gastritis tissues,dysplasia tissues,and GC tissues by qRT-PCR.?4?Analyze the relationship between hsa_circ₀006633 expression and clinicopathological factors as well as prognosis in GC patients.?5?The expression level of hsa_circ₀006633 in the plasma of healthy volunteers and early gastric cancer?EGC?patients was compared.?6?The stability of human plasma hsa_circ₀006633 was identified.Results?1?We found that hsa_circ₀006633 was significantly downregulated in four gastric cancer cell lines,HGC-27,SGC-7901,MGC-803,and AGS than the normal gastric epithelial cell line GES-1.?2?Hsa_circ₀006633 expression levels were significantly downregulated in 79.2 %?76/96?gastric cancer tissues compared with the adjacent normal tissues.The area under the ROC curve was 0.741 and its sensitivity and specificity were 60.42 % and 81.25 %,respectively.?3?Hsa_circ₀006633 expression levels were significantly decreased in dysplasia tissues and cancer tissues comparing with the healthy control.?4?Hsa_circ₀006633 expression level was associated with distal metastasis?P = 0.037?and tissue CEA level?P = 0.041?in human gastric cancer tissues.?5?Kaplan-Meier survival curve showed that patients in high tissue hsa_circ₀006633 group had a shorter overall survival than those in low group.?6?The expression levels of hsa_circ₀006633 were significantly increased in patients' plasma of EGC compared with the healthy control.Hsa_circ₀006633 could be found in human plasma with good stability and meet the requirements of clinical examinations.ConclusionsOur study implies that gastric cancer associated circRNA hsa_circ₀006633 may play an important role in gastric carcinogenesis and is also a potential biomarker for early gastric cancer screening.