Lu Jun, Zhang Peng-Yang, Xie Jian-Wei, Wang Jia-Bin, Lin Jian-Xian, Chen Qi-Yue, Cao Long-Long, Huang Chang-Ming, Li Ping, Zheng Chao-Hui
Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China.
Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China.
J Clin Lab Anal. 2019 Mar;33(3):e22726. doi: 10.1002/jcla.22726. Epub 2018 Nov 21.
Emerging evidence indicates that dysregulation of circular RNAs (circRNAs) is implicated in the development of malignancies. However, the diagnostic value and functional role of circRNAs in gastric cancer (GC) remain largely elusive.
Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was performed to detect the expression of hsa_circ_0000467 in tissues, cell lines, and plasma. A receiver operating characteristic (ROC) curve was constructed to estimate the diagnostic value of hsa_circ_0000467. The association between the expression level of hsa_circ_0000467 and the clinicopathological features was analyzed. Moreover, cell functional assays were performed.
Hsa_circ_0000467 was significantly upregulated in GC tissue compared to adjacent nontumor tissue (n = 51, P < 0.05). Similar results were detected in the HGC-27, MGC-803, AGS, NUGC-3, GES-1 cell lines (n = 15, P < 0.001), and in the plasma samples from GC patients (n = 20, P < 0.05). The area under the ROC curve of hsa_circ_0000467 was 0.790, which is superior to commonly used biomarkers including CEA and CA-724. We found that the expression levels of hsa_circ_0000467 in the same patient were significantly lower after surgery (n = 20, P < 0.05). Moreover, the hsa_circ_0000467 expression level is closely associated with TNM stage. Additionally, Cox multivariate analysis showed that hsa_circ_0000467 is a novel independent prognostic factor. Furthermore, in vitro experiments demonstrated that knockdown of hsa_circ_0000467 markedly inhibited the proliferation, migration, and invasion of GC cells. Moreover, hsa_circ_0000467 silencing increased tumor apoptosis in vitro.
Hsa_circ_0000467 can act as a novel noninvasive biomarker for the diagnosis and prognosis of GC and may be a potential therapeutic target for GC.
新出现的证据表明,环状RNA(circRNA)失调与恶性肿瘤的发生发展有关。然而,circRNA在胃癌(GC)中的诊断价值和功能作用仍不清楚。
采用定量逆转录聚合酶链反应(qRT-PCR)检测hsa_circ_0000467在组织、细胞系和血浆中的表达。构建受试者工作特征(ROC)曲线以评估hsa_circ_0000467的诊断价值。分析hsa_circ_0000467表达水平与临床病理特征之间的关联。此外,进行细胞功能实验。
与癌旁非肿瘤组织相比,hsa_circ_0000467在GC组织中显著上调(n = 51,P < 0.05)。在HGC-27、MGC-803、AGS、NUGC-3、GES-1细胞系中也检测到类似结果(n = 15,P < 0.001),以及在GC患者的血浆样本中(n = 20,P < 0.05)。hsa_circ_0000467的ROC曲线下面积为0.790,优于常用生物标志物,包括癌胚抗原(CEA)和糖类抗原724(CA-724)。我们发现,同一患者术后hsa_circ_0000467的表达水平显著降低(n = 20,P < 0.05)。此外,hsa_circ_0000467表达水平与TNM分期密切相关。另外,Cox多因素分析显示hsa_circ_0000467是一个新的独立预后因素。此外,体外实验表明,敲低hsa_circ_0000467可显著抑制GC细胞的增殖、迁移和侵袭。而且,hsa_circ_0000467沉默可增加体外肿瘤细胞凋亡。
hsa_circ_0000467可作为GC诊断和预后的新型非侵入性生物标志物,可能是GC的潜在治疗靶点。