scholarly journals Identification of Plasma hsa_circ_0005397 and Combined With Serum AFP, AFP-L3 as Potential Biomarkers for Hepatocellular Carcinoma

2021 ◽  
Vol 12 ◽  
Author(s):  
Ruoyu Liu ◽  
Yi Li ◽  
Anqi Wu ◽  
Mingzhu Kong ◽  
Weijia Ding ◽  
...  

Background: Mounting evidence has demonstrated that circular RNA (circRNA) plays crucial roles in the occurrence and development of hepatocellular carcinoma (HCC). However, the expression pattern and clinical application value of plasma circRNA in HCC are still largely unknown. Herein, we explored the role of plasma hsa_circ_0005397 in diagnosis and prognosis of HCC.Methods: The expression level of plasma hsa_circ_0005397 was measured by quantitative real-time polymerase chain reaction (qRT-PCR). The identification and origin of plasma hsa_circ_0005397 were confirmed by RNase R assay, Sanger sequencing and HCC cell culture. In addition, its diagnostic value was assessed by receiver operating characteristic (ROC) curve and prognostic value was evaluated by dynamics monitoring and Kaplan–Meier curve analyses in HCC patients.Results: The expression of plasma hsa_circ_0005397 was higher in patients with HCC than that in patients with benign liver diseases and healthy controls (both p < 0.05). Moreover, it was closely correlated with tumor size (p = 0.020) and TNM stage (p = 0.006) of HCC patients. The area under the ROC curve of plasma hsa_circ_0005397 was 0.737 and 95% confidence interval was 0.671–0.795. Furthermore, the combination of plasma hsa_cic_0005397, serum AFP and AFP-L3 could improve the diagnostic sensitivity of HCC. Additionally, dynamic monitoring plasma hsa_cic_0005397 might help us predict recurrence or metastasis in HCC patients after surgical resection. Besides, the increased plasma hsa_cic_0005397 was closely correlated with shorter overall survival of HCC patients (p = 0.007).Conclusion: Plasma has_circ_0005397 represents a novel noninvasive biomarker for HCC. Moreover, the combination of plasma hsa_cic_0005397, serum AFP and AFP-L3 might improve the diagnostic value for HCC.

2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Liangwei Yang ◽  
Yu Yu ◽  
Xiuchong Yu ◽  
Jiaming Zhou ◽  
Zhiping Zhang ◽  
...  

Background. Gastric cancer (GC) has a poor prognosis due to the lack of ideal tumor markers. Circular RNAs (circRNAs) are a novel type of noncoding RNA related to the occurrence of GC. Among our research, we investigated the role of hsa_circ_0005556 in GC. Materials and Methods. The expression of hsa_circ_0005556 of 100 paired GC tissues and adjacent normal tissues was detected using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). A receiver operating characteristic (ROC) curve was established to evaluate the diagnostic value of hsa_circ_0005556. The correlation between the expression of hsa_circ_0005556 and corresponding clinicopathological characteristic was explored. Results. hsa_circ_0005556 was significantly downregulated in GC tissues contrasted with adjacent normal tissues (n=100, p<0.001). The areas under the ROC curve (AUC) of hsa_circ_0005556 were up to 0.773, while 64% sensitivity and 82% specificity, respectively. Moreover, its expression levels were significantly associated with differentiation (p=0.001), TNM stage (p=0.013), and lymphatic metastasis (p=0.039). GC patients of high hsa_circ_0005556 levels had a longer overall survival (OS) than those of the low group (p=0.047). Conclusion. hsa_circ_0005556 is a potential biomarker for GC, which may guide judgment of the indication of endoscopic treatment for early gastric cancer (EGC).


2021 ◽  
Vol 11 ◽  
Author(s):  
Tao Ma ◽  
Yue Ma ◽  
Yongjun Du ◽  
Zhongheng Wei ◽  
Jianchu Wang ◽  
...  

Backgroundcirc0013958 was identified as a biomarker, which can be used for the diagnosis and screening of lung cancer. However, the role of circ0013958 in hepatocellular carcinoma (HCC) remains unclear.MethodsIn our study, quantitative real-time polymerase chain reaction was performed to determine the levels of circ0013958 in HCC tissues and cell lines. EdU, CCK-8, transwell, flow cytometry and tumorigenesis assays were applied to assess the functions of circ0013958 in HCC in vitro and in vivo. Western blot assay was to detect the expression of WEE1. Luciferase reporter assay, bioinformatics analysis and rescue experiments were used to examine the interaction among circ0013958, miR-532-3p and WEE1.ResultsIt revealed that circ0013958 was significantly up-regulated in HCC, which was positively correlated with poor prognosis of HCC patients. Circ0013958 promoted HCC cell proliferation and invasion, inhibited cell apoptosis in vitro, and promoted tumorigenesis in vivo. Circ0013958 acted as a miR-532-3p sponge to regulate WEE1 expression, thus promoting the progression of HCC.ConclusionsCirc0013958 promotes HCC progression through miR-532-3p/WEE1 axis. Circ0013958 may serve as a potential diagnostic biomarker and therapeutic target of HCC.


2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Dao-xiong Ye ◽  
Si-si Wang ◽  
Ying Huang ◽  
Pan Chi

Abstract Background Circular RNAs (circRNAs), a novel type of noncoding RNAs, play critical roles in the initiation and progression of cancer. Emerging studies also shows that circRNAs may function as potential markers for cancer diagnosis and treatment. However, the diagnostic value of circRNAs in colorectal cancer (CRC) remains need to be unearthed. Methods CircRNA microarray was performed to detect the differentially expressed circRNAs in eight plasma samples, including four colorectal cancer (CRC) and four normal samples. Besides, the results of microarray were validated by quantitative real-time polymerase chain reaction (qRT-PCR). Moreover, ROC curve evaluation was performed to calculate the diagnostic value of significantly dysregulated circRNAs. In order to predict the potential mechanism of the significant circRNAs, circRNA–miRNA–mRNA network was constructed based on the TargetScan, miRTarBase and MIRDB database, as well as CircInteractome online software. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to further predict the function of meaningful circRNAs. Results Totally three differentially expressed circRNAs were identified in CRC plasma compared to normal plasma by circRNA microarray analysis, and the results was validated by qRT-PCR. Hsa_circ_0082182, hsa_circ_0000370 and hsa_circ_0035445 were identified and ROC curves analysis was used to calculate the single and joint diagnostic value. Furthermore, GO and KEGG analyses revealed that functions were mainly cancer-related, which indicated that the circRNAs were meaningfully associated with CRC cell proliferation and metastasis. Conclusion In conclusion, we have identified three circRNAs that are dysregulated in CRC plasma, including hsa_circ_0082182, hsa_circ_0000370 and hsa_circ_0035445. ROC curves showed that these circRNAs might have diagnostic value for colorectal cancer. Furthermore, bioinformatics analysis indicated that the above-mentioned circRNAs might be involved in the development of CRC.


2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Jun Lu ◽  
Peng-yang Zhang ◽  
Jian-wei Xie ◽  
Jia-bin Wang ◽  
Jian-xian Lin ◽  
...  

Objective. Circular RNAs (circRNAs) have been reported to be widely involved in pathological processes of various cancers. However, little is known about their diagnostic values in early gastric cancer (EGC). This study is aimed at exploring whether circulating circRNAs in plasma could act as biomarkers for EGC diagnosis. Materials and Methods. Mass spectrometry (MS) was performed to identify the proteins that at significantly aberrantly levels in gastric cancer (GC) tissues. The target circRNA was identified by bioinformatics analysis. A receiver operating characteristic (ROC) curve was generated to evaluate the diagnostic utility. Results. MS revealed that the ribosomal protein L6 (RPL6) expression was significantly downregulated only in EGC tissues vs. nontumorous tissues; this was validated by western blotting (n=30, p=0.0094). Bioinformatics analysis predicted that there is a hsa_circ_0006848/hsa_miR-329-5p/RPL6 axis in GC progression. The hsa_circ_0006848 expression was significantly downregulated in EGC tissues (vs. nontumorous tissues, n=30, p=0.0073) and plasma samples from EGC patients (vs. paired healthy volunteers, n=30, p=0.0089). In addition, the hsa_circ_0006848 plasma level in postoperative patients was significantly higher than that of preoperative patients (n=30, p=0.047). Furthermore, the decreased hsa_circ_0006848 expression in plasma was negatively correlated with poor differentiation (p=0.037) and tumor size (p=0.046). The area under the ROC curve (AUC) of hsa_circ_0006848 in plasma was 0.733, suggesting a good diagnostic value. The plasma hsa_circ_0006848 level combined with the carcinoembryonic antigen (CEA), carbohydrate-associated antigen 19-9 (CA19-9), and carbohydrate-associated antigen 72-4 (CA72-4) level increased the AUC to 0.825. Conclusion. Our results indicated that plasma hsa_circ_0006848 may be a novel noninvasive biomarker in EGC diagnosis.


2021 ◽  
Vol 11 (3) ◽  
pp. 219
Author(s):  
Ya-Ling Yang ◽  
Yen-Hsiang Chang ◽  
Chia-Jung Li ◽  
Ying-Hsien Huang ◽  
Ming-Chao Tsai ◽  
...  

Hepatocellular carcinoma (HCC) remains one of the most lethal human cancer globally. For advanced HCC, curable plan for advanced HCC is yet to be established, and the prognosis remains poor. The detail mechanisms underlying the progression of HCC tumorigenicity and the corruption of tumor microenvironment (TME) is complex and inconclusive. A growing body of studies demonstrate microRNAs (miRs) are important regulators in the tumorigenicity and TME development. Notably, mounting evidences indicate miR-29a play a crucial role in exerting hepatoprotective effect on various types of stress and involved in the progression of HCC, which elucidates their potential theragnostic implications. In this review, we reviewed the advanced insights into the detail mechanisms by which miR-29a dictates carcinogenesis, epigenetic program, and metabolic adaptation, and implicated in the sponging activity of competitive endogenous RNAs (ceRNA) and the TME components in the scenario of HCC. Furthermore, we highlighted its clinical significance in diagnosis and prognosis, as well as the emerging therapeutics centered on the activation of miR-29a.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yanxia Zhang ◽  
Huiyun Wang ◽  
Yu Xia

Abstract Background The purpose of this study was to evaluate the diagnostic and prognostic significance of miR-211-5p in atherosclerosis (AS) by detecting the expression level in serum of patients with AS. Methods A total of 85 healthy controls and 90 asymptomatic AS patients participated in this study. The expression level of miR-211-5p in all subjects were measured by qRT-PCR. Spearman correlation coefficient was used to evaluate the correlation of miR-211-5p with CRP and CIMT. The ROC curve was established to assess the diagnostic value of miR-211-5p in AS. The Kaplan–Meier survival curve and multivariate COX regression analysis were used to evaluate the prognostic significance of miR-211-5p in AS. Results The expression levels of miR-211-5p in AS patients were significantly lower than in healthy controls (P < 0.001), and miR-211-5p showed a significant negative correlation with CRP (r =  − 0.639, P < 0.001) and CIMT (r =  − 0.730, P < 0.001). The AUC of the ROC curve was 0.900, the specificity and the sensitivity were 84.7% and 78.9%, respectively, which indicating that miR-211-5p had diagnostic value for AS. Survival analysis showed that patients with low miR-211-5p expression were more likely to have cardiovascular end-point events (Log rank P = 0.013). Conclusion Serum miR-211-5p could be used as a new biomarker for the diagnosis of AS, and the low expression of miR-211-5p is associated with the poor prognosis of AS.


2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Ya-Wen Lin ◽  
Yu-Lueng Shih ◽  
Gi-Shih Lien ◽  
Fat-Moon Suk ◽  
Chung-Bao Hsieh ◽  
...  

Oncogenic activation of the Wnt/β-catenin signaling pathway is common in human cancers. The secreted frizzled-related proteins (SFRPs) function as negative regulators of Wnt signaling and have important implications in carcinogenesis. Because there have been no reports about the role ofSFRP3in hepatocellular carcinoma (HCC), we investigated the level of methylation and transcription ofSFRP3. Four HCC cell lines, 60 HCCs, 23 cirrhosis livers, 37 chronic hepatitis livers, and 30 control livers were prescreened forSFRP3promoter methylation by methylation-specific polymerase chain reaction (MS-PCR) and bisulfite sequencing.SFRP3promoter methylation was observed in 100%, 60%, 39.1%, 16.2%, and 0% in HCC cell lines, primary HCCs, cirrhosis livers, chronic hepatitis livers, and control livers, respectively. Demethylation treatment with 5-aza-2′-deoxycytidine in HCC cells restored or increased theSFRP3mRNA expression. We next used quantitative MS-PCR (QMSP) to analyze the methylation level ofSFRP3in 60 HCCs and their corresponding nontumor tissues. Methylation ofSFRP3promoter region in HCCs increased significantly compared with control tissues. There is a positive correlation between promoter hypermethylation andSFRP3mRNA downregulation. Our data suggest that promoter hypermethylation ofSFRP3is a common event in HCCs and plays an important role in regulation ofSFRP3mRNA expression.


2021 ◽  
Author(s):  
Chenjuan Peng ◽  
Chen Yang ◽  
Jincao Yao ◽  
LingYan Zhou ◽  
Jingjing Xu ◽  
...  

Abstract Objective Sixty-nine patients with primary thyroid lymphoma (PTL) were evaluated for diagnostic value and prognosis for PTL invasiveness. Methods We retrospectively (2008–2019) analyzed multi-modal ultrasonic images and clinical characteristics from pathologically confirmed PTL patients. These patients were divided into aggressive PTL(n=46) and indolent PTL(n=23). Results Age(>70 years old) and elevated LDH (lactase dehydrogenase) were statistically different clinical features between aggressive and indolent PTL. From ultrasonic images, 34 cases were nodular, 11 diffused, and 24 mixed. Mixed types displayed high invasiveness (45.7%) while diffuse types displayed higher inertness (39.1%), and differences were statistically significant (P = 0.000). Elastography, invaded thyroid capsule and increased chaotic vascularity also showed significant differences between aggressive and indolent PTL. We observed statistical difference in OS(overall survival rates) between aggressive and indolent PTL(p=0.032). Single factor Kaplan-Meier (K-M) analysis showed that: age > 70 years old, aggressive pathology, Ki67>30%, elastography scored >3 were positively correlated with the risk of poor prognosis of PTL (P < 0.05).Conclusions Multi-modal ultrasound provides accurate ultrasonographic information, e.g., ultrasound patterns, elastography, invaded thyroid capsules, and hypervascularity, which facilitates PTL invasiveness diagnostics for improved clinical treatment. In addition, PTL patients with age > 70 years old, aggressive pathology, Ki67>30%, elastography scored >3 are more likely to have poor prognosis.


2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Melika Ameli-Mojarad ◽  
Mandana Ameli-Mojarad ◽  
Mitra Nourbakhsh ◽  
Ehsan Nazemalhosseini-Mojarad

Breast cancer (BC) is one of the most common lethal diseases in women worldwide. Recent evidence has shown that covalently closed Circular RNA (circRNA) deregulation is observed in different human malignancies and cancers. Lately, circRNAs are being considered as a new diagnostic biomarker; however, the mechanism and the correlation of action between circRNAs and BC are still unclear. In the present study, we try to investigate the expression level of hsa_circ_0005046 and hsa_circ_0001791 in BC. By using quantitative real-time polymerase chain reaction (qRT-PCR), expression profiles of candidate circRNAs were detected in 60 BC tissue and paired adjacent normal tissues. Furthermore, the clinicopathological relation and diagnostic value were estimated. Our results showed the higher expression levels of hsa_circ_0005046 and hsa_circ_0001791 in BC tissues compared to paired adjacent normal tissues with P value ( P < 0.0001 ) for both circRNAs, and the area under the receiver operating characteristic (ROC) curve was 0.857 and 1.0, respectively; in addition, a total 10 miRNAs that can be targeted by each candidate circRNAs was predicted base on bioinformatics databases. Taken together, for the first time, the results of our study presented high expression levels of hsa_circ_0005046 and hsa_circ_00017916 in BC; although there was no direct correlation between the high expression level of both circRNAs with clinic pathological factors, except hsa_circ_0001791 association with estrogen receptors (ER), high ROC curve in expressed samples indicated that both circRNAs could be used as a new diagnostic biomarker for BC. Moreover, miRNAs selection tools predicted that miR-215 and mir-383-5p which have a tumor suppressor role in BC can be targeted by our candidate circRNAs to affect the PI3K/AKT pathway; in conclusion, further studies are required to validate the oncogene role of our candidate circRNAs through the PI3k pathway.


2019 ◽  
Author(s):  
rui kong ◽  
Nan Wang ◽  
Wei Han ◽  
Yuejuan Zheng ◽  
Jie Lu

Abstract Background: In recent years, long non-coding RNAs (lncRNAs) are emerging as crucial regulators in the immunological process of liver hepatocellular carcinoma (LIHC). Increasing studies have found that some lncRNAs could be used as a diagnostic or therapeutic target for clinical management, but little research has investigated the role of immune-related lncRNA in tumor prognosis. In this study, we aimed to develop an immune lncRNA signature for the precise diagnosis and prognosis of liver hepatocellular carcinoma. Methods: Gene expression profiles of LIHC samples obtained from TCGA were screened for immune-related genes using two reference gene sets. The optimal immune-related lncRNA signature was built via correlational analysis, univariate and multivariate cox analysis. Then the Kaplan-Meier plot, ROC curve, clinical analysis, gene set enrichment analysis, and principal component analysis were carried out to evaluate the capability of immune lncRNA signature as a prognostic indicator. Results: Six long non-coding RNA MSC−AS1, AC009005.1, AL117336.3, AL031985.3, AL365203.2, AC099850.3 were identified via correlation analysis and cox regression analysis considering their interactions with immune genes. Next, tumor samples were separated into two risk groups by the signature with different clinical outcomes. Stratification analysis showed the prognostic ability of this signature acted as an independent factor. The AUC value of ROC curve was 0.779. The Kaplan-Meier method was used in survival analysis and results showed a statistical difference between the two risk groups. The predictive performance of this signature was validated by principal component analysis (PCA). Data from gene set enrichment analysis (GSEA) further unveiled several potential biological processes of these biomarkers may involve in. Conclusion: In summary, the study demonstrated the potential role of the six-lncRNA signature served as an independent prognostic factor for LIHC patients.


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