scholarly journals circSMARCA5 Functions as a Diagnostic and Prognostic Biomarker for Gastric Cancer

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Juan Cai ◽  
Zhiqiang Chen ◽  
Xueliang Zuo

Background. Circular RNAs have been implicated in various malignancies and can function as potential biomarkers for cancers. Reportedly, circSMARCA5 was downregulated in hepatocellular carcinoma and glioblastoma multiforme, but upregulated in prostate cancer. The functional roles and clinical significance of circSMARCA5 still remain unknown in the context of gastric cancer (GC). Methods. Expression levels of circSMARCA5 were detected by qRT-PCR. Clinical data including patient basic information, clinicopathological features, and survival data were obtained. The Kaplan-Meier methods, multivariate Cox regression models, and the receiver operating characteristic curve were used to assess the clinical significance of circSMARCA5 in GC. Cell proliferation assays and transwell assays were performed to elucidate the functional roles of circSMARCA5 in GC. Results. The circSMARCA5 level was decreased in GC tissues and cell lines. The low expression level of circSMARCA5 was correlated to poorer overall survival and disease-free survival. Low circSMARCA5 expression was revealed as an independent unfavorable predictive factor for GC. The results indicated that circSMARCA5 had a moderate ability for discrimination between GC patients and controls with an area under the curve of 0.806. Upregulation of circSMARCA5 dampened the proliferation, migration, and invasion of GC cells, whereas circSMARCA5 knockdown promoted GC progression. Discussion. Our results demonstrated that circSMARCA5 was decreased and exerted tumor-suppressive effects in GC. circSMARCA5 can function as a potential biomarker for GC prognosis and diagnosis.

2014 ◽  
Vol 138 (11) ◽  
pp. 1466-1473 ◽  
Author(s):  
Jiang-Liu Yu ◽  
Ping Lv ◽  
Jing Han ◽  
Xin Zhu ◽  
Lian-Lian Hong ◽  
...  

Context Fluid methylated DNA may be a suitable biomarker for cancer patients. Objective To investigate whether circulating methylated tissue inhibitor of metalloproteinase 3 (TIMP-3) DNA in body fluids is a useful prognostic biomarker in gastric cancer (GC). Design TIMP-3 methylation was detected by real-time methylation-specific polymerase chain reaction in tumor tissues, paired preoperative peritoneal washes (PPWs), and paired serum samples from 92 GC patients. Results The frequency of TIMP-3 methylation was significantly elevated in GC tissues (63.04%; 58 of 92) compared with that in paired adjacent normal tissue (4.3%; 4 of 92) (P < .001). TIMP-3 methylation correlated closely with peritoneal metastasis and TNM stage (all P < .001). The frequency of TIMP-3 methylation in preoperative peritoneal washes and serum samples was 53.3% (49 of 92) and 58.7% (54 of 92), respectively. The Aζ values of the receiver operator characteristic curve for methylated TIMP-3 were 0.966 and 0.922 for serum and preoperative peritoneal washes, respectively, compared with those in GC tissues. The patients with elevated methylated TIMP-3 levels in body fluids had poorer disease-free survival rates than those without (all P < .001). Cox regression analysis showed that detection of methylated TIMP-3 DNA in body fluids was an independent risk factor for GC patients, with a remarkable decrease in disease-free survival 30 months after surgical resection of the gastric tumor. Conclusion Presence of methylated TIMP-3 DNA in body fluids is a useful biomarker for predicting the progression and prognosis of GC patients.


2021 ◽  
Vol 8 ◽  
Author(s):  
Guo-Dian Zheng ◽  
Zhi-Yuan Xu ◽  
Can Hu ◽  
Hang Lv ◽  
Hua-Xia Xie ◽  
...  

The purpose of this study is to explore the expression of miRNA-590-5p, an exosome of gastric cancer (GC), and to evaluate the suitability of miR-590-5p, an exosome with its own clinical characteristics. Serum samples from 168 gastric cancer patients and 50 matched controls were collected and exosomal RNAs were extracted. After that, miR-590-5p is analyzed by quantitative polymerase chain reaction (qRT-PCR), which is more related to clinical and pathological parameters and patient monitoring data. MGC-803 and HGC-27 cells were treated by miR-590-5p mimics, and then the changes of cell fluidity and invasiveness were monitored. The results showed that the expression level of miR-590-5p in exosomes of healthy observation group, early (I and II) stage group, and late stage (III) group was 30.34 ± 6.35, 6.19 ± 0.81, and 2.9 ± 0.19, respectively (all p < 0.05). ROC (receiver-operating characteristic curve) showed that the AUC (area under the curve) of exosomal miR-590-5p was 0.810 with 63.7% sensitivity and 86% specificity. The expression of exosomal miR-590-5p in serum was related to clinical stage (p = 0.008), infiltration depth, and the expression level of ki-67 (p < 0.001). In addition, Kaplan-Meier analysis showed that the decrease of explicit level of exosomal miR-590-5p was related to the decrease of overall survival rate (p < 0.001). Cox regression analysis showed that miR-590-5p can be used as an independent predictor. Furthermore, upregulation of miR-590-5p inhibited cell migration and invasion in MGC-803 cells and HGC-27 cells. The serum expression level of exosomal miR-590-5p may be a biomarker, which is potentially useful and noninvasive for early detection and prediction of GC. In addition, miR-590-5p can play a role in eliminating carcinogens by actively regulating the malignant potential of gastric cancer.


2021 ◽  
Vol 12 (10) ◽  
Author(s):  
Shuo Ma ◽  
Xinliang Gu ◽  
Lei Shen ◽  
Yinhao Chen ◽  
Chen Qian ◽  
...  

AbstractGastric cancer (GC) is considered one of the most common gastrointestinal malignancies worldwide. Circular RNAs (circRNAs) are a new class of endogenous noncoding RNAs, which can be used as biomarkers and therapeutic targets for many tumors. However, the role and potential regulatory mechanisms of circRNAs in GC remain unclear. In this study, we demonstrated that a specific circRNA, circHAS2, was upregulated in GC tissues and cells and was positively correlated with tumor metastasis. In vitro experiments demonstrated that circHAS2 knockdown or the addition of hsa-miR-944 mimics inhibited the proliferation, migration, and invasion ability of GC cells and affected the epithelial-mesenchymal transition. In addition, hsa-miR-944 interacted with protein phosphatase, Mg2+/Mn2+-dependent 1E (PPM1E), and was found to be a target gene of circHAS2. The upregulation of PPM1E reversed the effects of circHAS2 knockout on GC cells. The circHAS2/hsa-miR-944/PPM1E axis may be involved in the progression of GC; thus, circHAS2 may be a potential biomarker and therapeutic target for GC.


2021 ◽  
Vol 11 ◽  
Author(s):  
Lei Yang ◽  
Yong-ning Zhou ◽  
Miao-miao Zeng ◽  
Nan Zhou ◽  
Bin-sheng Wang ◽  
...  

BackgroundCircular RNAs (circRNAs) are closely associated with the occurrences and progress of gastric cancer (GC). We aimed to delve into the function and pathological mechanism of Circular RNA-0002570 (circ-0002570) in GC progression.MethodsCircRNAs differentially expressed in GC were screened using bioinformatics technology. The expression of circ-0002570 was detected in GC specimens and cells via qRT-PCR, and the prognostic values of circ-0002570 were determined. The functional roles of circ-0002570 on proliferation, migration, and invasion in GC cells were explored in vitro and in vivo. Interaction of circ-0002570, miR-587, and VCAN was confirmed by dual-luciferase reporter assays, Western blotting, and rescue experiments.ResultsCirc-0002570 expression was distinctly increased in GC tissues compared to adjacent normal specimens, and GC patients with higher circ-0002570 expressions displayed a short survival. Functionally, knockdown of circ-0002570 resulted in the inhibition of cell proliferation, migration, and invasion, and suppressed tumor growth in vivo. Mechanistically, miR-587 was sponged by circ-0002570. VCAN expression in NSCLC was directly inhibited by miR-587. Overexpression of circ-0002570 prevented VCAN from miR-587-mediated degradation and thus facilitated GC progression.ConclusionThe circ-0002570-miR-587-VCAN regulatory pathway promoted the progression of GC. Our findings provided potential new targets for the diagnosis and therapy of GC.


2021 ◽  
Vol 28 (1) ◽  
Author(s):  
Qi Shi ◽  
Chuanwen Zhou ◽  
Rui Xie ◽  
Miaomiao Li ◽  
Peng Shen ◽  
...  

Abstract Background Circular RNAs (circRNAs) have been reported to play an important role in tumor progression in various cancer types, including gastric cancer. The aim of this study was to investigate the role of circCNIH4 (hsa_circ_0000190) in gastric cancer and the underlying mechanism. Methods The expression levels of circCNIH4 and Wnt antagonist genes were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The protein levels of β-catenin, Ki67, Dickkopf 2 (DKK2) and Frizzled related protein (FRZB) were measured by western blot. Ectopic overexpression or knockdown of circCNIH4, proliferation, apoptosis, migration and invasion by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT), flow cytometry and transwell assay in vitro, and in vivo experiment, were employed to assess the role of circCNIH4 in gastric cancer. Results CircCNIH4 was downregulated in gastric cancer tissues and cells. Overexpression of circCNIH4 inhibited gastric cancer cell proliferation, migration and invasion and promoted apoptosis by inactivating Wnt/β-catenin pathway in vitro. CircCNIH4 induced the expression of DKK2 and FRZB in gastric cancer cells. Moreover, silencing of DKK2 or FRZB reversed circCNIH4 overexpression-mediated effects on gastric cancer cells. Additionally, circCNIH4 suppressed tumor growth via regulating DKK2 and FRZB expression in gastric cancer in vivo. Conclusion Our study demonstrated that circCNIH4 played a tumor-inhibiting role through upregulating DKK2 and FRZB expression and suppressing Wnt/β-catenin pathway in gastric cancer, which might provide a potential biomarker for the diagnosis and treatment of gastric cancer.


2021 ◽  
Vol 20 ◽  
pp. 153303382098330
Author(s):  
Xianbo Shen ◽  
Yun Chen ◽  
Jibin Li ◽  
Huaiyin Huang ◽  
Chuping Liu ◽  
...  

Emerging evidence has shown that circular RNAs (circRNAs) serve as a promising biomarker in different malignancies. Specifically, circ_001569 has been found to be upregulated in some types of human gastrointestinal cancer. In this study, we aimed to investigate clinical significances, diagnostic and prognostic values of circ_001569 in pancreatic cancer (PC), and identify its effects on the malignant behaviors of PC cells. The expression of circ_001569 was determined in 26 tissues samples and 97 plasma samples from PC patients by qRT-PCR. Relationship between circ_001569 expression and clinicopathological parameters was analyzed by Chi-square test. Diagnostic and prognostic values of circ_001569 were evaluated by ROC curves, Kaplan-Meier curves, and Cox regression analysis. The effects of circ_001569 on the proliferation, migration, invasion, and apoptosis of PC cells were assessed by MTT, wound healing, Transwell invasion assays, and flow cytometric analysis, respectively. Results showed that the expression of circ_001569 was upregulated in tissues and plasma of PC patients. High circ_001569 level was positively correlated with lymphatic metastasis, clinical stage, and venous invasion. Circ_001569 level was an independent prognostic indicator for overall survival rates of PC patients, and patients with high circ_001569 level had a poor prognosis. The AUC of circ_001569 was 0.716 (95% CI: 0.642-0.790) with a sensitivity and specificity of 62.76% and 74.29%, respectively. In vitro, circ_001569 silencing decreased cell proliferation, migration, and invasion, but promoted cell apoptosis of PC cells. Our data demonstrate that high circ_001569 level associates with tumor malignant behaviors, and may serve as a potential biomarker in the diagnosis and prognosis of PC.


2020 ◽  
Vol 15 ◽  
Author(s):  
Yuan Gu ◽  
Ying Gao ◽  
Xiaodan Tang ◽  
Huizhong Xia ◽  
Kunhe Shi

Background: Gastric cancer (GC) is one of the most common malignancies worldwide. However, the biomarkers for the prognosis and diagnosis of Gastric cancer were still need. Objective: The present study aimed to evaluate whether CPZ could be a potential biomarker for GC. Method: Kaplan-Meier plotter (http://kmplot.com/analysis/) was used to determine the correlation between CPZ expression and overall survival (OS) and disease-free survival (DFS) time in GC [9]. We analyzed CPZ expression in different types of cancer and the correlation of CPZ expression with the abundance of immune infiltrates, including B cells, CD4+ T cells, CD8+ T cells, neutrophils, macrophages, and dendritic cells, via gene modules using TIMER Database. Results: The present study identified that CPZ was overexpressed in multiple types of human cancer, including Gastric cancer. We found that overexpression of CPZ correlates to the poor prognosis of patients with STAD. Furthermore, our analyses show that immune infiltration levels and diverse immune marker sets are correlated with levels of CPZ expression in STAD. Bioinformatics analysis revealed that CPZ was involved in regulating multiple pathways, including PI3K-Akt signaling pathway, cGMP-PKG signaling pathway, Rap1 signaling pathway, TGF-beta signaling pathway, regulation of cell adhesion, extracellular matrix organization, collagen fibril organization, collagen catabolic process. Conclusion: This study for the first time provides useful information to understand the potential roles of CPZ in tumor immunology and validate it to be a potential biomarker for GC.


2020 ◽  
Vol 14 (12) ◽  
pp. 1127-1137
Author(s):  
Tong-Tong Zhang ◽  
Yi-Qing Zhu ◽  
Hong-Qing Cai ◽  
Jun-Wen Zheng ◽  
Jia-Jie Hao ◽  
...  

Aim: This study aimed to develop an effective risk predictor for patients with stage II and III colorectal cancer (CRC). Materials & methods: The prognostic value of p-mTOR (Ser2448) levels was analyzed using Kaplan–Meier survival analysis and Cox regression analysis. Results: The levels of p-mTOR were increased in CRC specimens and significantly correlated with poor prognosis in patients with stage II and III CRC. Notably, the p-mTOR level was an independent poor prognostic factor for disease-free survival and overall survival in stage II CRC. Conclusion: Aberrant mTOR activation was significantly associated with the risk of recurrence or death in patients with stage II and III CRC, thus this activated proteins that may serve as a potential biomarker for high-risk CRC.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jaeseung Shin ◽  
Joon Seok Lim ◽  
Yong-Min Huh ◽  
Jie-Hyun Kim ◽  
Woo Jin Hyung ◽  
...  

AbstractThis study aims to evaluate the performance of a radiomic signature-based model for predicting recurrence-free survival (RFS) of locally advanced gastric cancer (LAGC) using preoperative contrast-enhanced CT. This retrospective study included a training cohort (349 patients) and an external validation cohort (61 patients) who underwent curative resection for LAGC in 2010 without neoadjuvant therapies. Available preoperative clinical factors, including conventional CT staging and endoscopic data, and 438 radiomic features from the preoperative CT were obtained. To predict RFS, a radiomic model was developed using penalized Cox regression with the least absolute shrinkage and selection operator with ten-fold cross-validation. Internal and external validations were performed using a bootstrapping method. With the final 410 patients (58.2 ± 13.0 years-old; 268 female), the radiomic model consisted of seven selected features. In both of the internal and the external validation, the integrated area under the receiver operating characteristic curve values of both the radiomic model (0.714, P < 0.001 [internal validation]; 0.652, P = 0.010 [external validation]) and the merged model (0.719, P < 0.001; 0.651, P = 0.014) were significantly higher than those of the clinical model (0.616; 0.594). The radiomics-based model on preoperative CT images may improve RFS prediction and high-risk stratification in the preoperative setting of LAGC.


2021 ◽  
Vol 11 (8) ◽  
pp. 1466-1476
Author(s):  
Xuli Wang ◽  
Aiping Wang

Circular RNAs (circRNAs) have been reported to participate in the molecular mechanism of human cancers. This study investigates the role of circRNA hsa_circ_0000515 in gastric cancer (GC) cells and the underlying mechanism associated with microRNA-615-5p (miR-615-5p). qRT-PCR analysis showed the upregulation of hsa_circ_0000515 and downregulation of miR-615-5p in GC cell lines. Loss-of-function experiments indicated that suppression of hsa_circ_0000515 inhibited cell proliferation, migration, and invasion. Dual-luciferase reporter assay highlighted that hsa_circ_0000515 was able to act as a ceRNA of miR-615-5p. Furthermore, hsa_circ_0000515 could interact with splicing factors and bind miR-615-5p to regulate progression of GC cells. Deficiency of miR-615-5p reverses the inhibitory roles of si-hsa_circ_0000515 on the proliferation, migration, and invasion of GC cells. The findings highlighted the promising uses of hsa_circ_0000515 as a likely novel target for gastric cancer treatment.


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