Comprehensive Assessment of Plasma-Derived circ_0004771 as a Potential Biomarker in Tracking the Progression of Gastric Cancer

Abstract Background: Due to the lack of specific and sensitive detection indicators, most patients with gastric cancer (GC) are already in the advanced stage at the time of diagnosis, resulting in a higher mortality. Therefore, it is urgent to search for effective diagnostic biomarkers with high specificity that can be applied in clinic. Methods: We screened out circ_0004771 through circRNA sequencing performed on three pairs of GC tissues and corresponding paracancerous tissues. Both exonuclease digestion assay, agarose gel electrophoresis (AGE) and sanger sequencing verified the potential of circ_0004771 being a biomarker. Additionally, we established quantitative real-time fluorescent Polymerase Chain Reaction (qRT-PCR) to detect the expression level of circ_0004771 and evaluated the methodology. What’s more, we collected plasma samples from GC patients, precancerous patients and gastritis patients, and we constructed the receiver operating characteristic curve (ROC) to appraise its diagnostic efficacy. Meanwhile, we collected the clinicopathological data of the patients to analyze the relationship between the expression level of circ_0004771 and the pathological parameters of the patients. Results: The expression level of circ_0004771 is up-regulated both in GC tissues and cells compared to normal controls. Circ_0004771 can be served as a promising biomarker because of its stable cyclic structure and longer half-life. The expression level of plasma circ_0004771 can distinguish between GC patients and precancerous patients, GC patients and gastritis patients. The diagnostic efficiency of circ_0004771 is higher than that of CEA and CA199. Higher diagnostic efficiency can be achieved in combination diagnosis. The expression level of plasma circ_0004771 in GC patients decreased after surgery, which can track the recovery condition of patients. Besides, the downstream regulatory forecast indicates that circ_0004771 may act as miRNA sponge to regulate the progression of GC.Conclusion: Plasma circ_0004771 can be served as a less invasive tumor biomarker with high diagnostic values.

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LncRNA HCP5 : A Potential Biomarker for Diagnosing Gastric Cancer

Frontiers in Oncology ◽

10.3389/fonc.2021.684531 ◽

2021 ◽

Vol 11 ◽

Author(s):

Shiyi Qin ◽

Lei Yang ◽

Shan Kong ◽

Yanhua Xu ◽

Bo Liang ◽

...

Keyword(s):

Gastric Cancer ◽

Expression Level ◽

Diagnostic Efficiency ◽

Early Screening ◽

Multiple Cancer ◽

Qrt Pcr ◽

Primary Gastric Cancer ◽

Healthy Donors ◽

Potential Biomarker ◽

Gastric Cancer Patients

BackgroundIt has been reported that long non-coding RNAs (lncRNAs) can be regarded as a biomarker and had particular clinical significance for early screening and gastric cancer (GC) diagnosis. Therefore, this study aimed to investigate whether serum HCP5 could be a new diagnostic biomarker.MethodsFiltered out the HCP5 from the GEO database. The specificity of HCP5 was verified by real-time fluorescence quantitative PCR (qRT-PCR), and then the stability of HCP5 was verified by room temperature storage and repeated freeze-thaw experiments. Meanwhile, the accuracy of HCP5 was verified by agarose gel electrophoresis (AGE) and Sanger sequencing. Simultaneously, the expression level of serum HCP5 was detected by qRT-PCR in 98 patients with primary gastric cancer, 21 gastritis patients, 82 healthy donors, and multiple cancer types. Then, the methodology analysis was carried on. Moreover, receiver operating characteristic (ROC) was used to evaluate its diagnostic efficiency.ResultsqRT-PCR method had good repeatability and stability in detecting HCP5. The expression level of HCP5 in the serum of gastric cancer patients was remarkably higher than that of healthy controls, and it could distinguish gastritis patients from healthy donors. Besides, the expression of HCP5 was increased dramatically in MKN-45 and MGC-803. The FISH assay showed that HCP5 was mainly distributed in the cytoplasm of MKN-45 and BGC-823 cells. When HCP5 was combined with existing tumor markers, the diagnostic efficiency of HCP5 was the best, and the combined diagnosis of carcinoembryonic antigen (CEA), carbohydrate antigen199 (CA199), and HCP5 can significantly improve the diagnostic sensitivity. Besides, compared with the expression levels of thyroid cancer (THCA), colorectal cancer (CRC), and breast cancer (BRCA), serum HCP5 in gastric cancer was the most specific. Moreover, the high expression of serum HCP5 was related to differentiation, lymph node metastasis, and nerve invasion. The term of serum HCP5 after the operation was significantly lower than that of patients with primary gastric cancer.ConclusionSerum HCP5 can be used as a potential biomarker of non-invasive fluid biopsy, which had a unique value in the early diagnosis, development, and prognosis of gastric cancer.

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Circulating Exosomal miR-17-92 Cluster Serves as a Novel Non-Invasive Diagnostic Marker for Gastric Cancer Patients

10.21203/rs.3.rs-826985/v1 ◽

2021 ◽

Author(s):

Fei Liu ◽

Ye Han ◽

Dongbao Li ◽

Jun Zhou ◽

Jingjing Xu ◽

...

Keyword(s):

Gastric Cancer ◽

Malignant Tumors ◽

Quantitative Polymerase Chain Reaction ◽

Characteristic Curve ◽

Diagnostic Value ◽

Diagnostic Efficiency ◽

Roc Curve Analysis ◽

Non Invasive ◽

Clinical Diagnostic ◽

Potential Biomarker

Abstract Gastric cancer (GC) is one of the most common malignant tumors with a leading cause of cancer-related mortality worldwide. Exosomal miRNAs are considered as promising non-invasive biomarkers for the diagnosis of malignant tumors. In this study, we aimed to investigate the expression of exosomal miR-17-92 cluster and develop a potential biomarker for the diagnosis of GC. Exosomal RNAs were extracted and the expression profile of miR-17-92 cluster was detected using quantitative polymerase chain reaction (qRT-PCR). The ROC (receiver-operating characteristic) curve and AUC (area under the ROC curve) analysis were used to explore the diagnostic utility of miRNAs. Statistical was used to analyze the expression of serum exosomal miR-17-92 cluster with the clinical pathological parameters of GC patients. The results showed that the expressions of four members of the exosomal miR-17-92 cluster in the serum samples of GC patients were significantly upregulated compared with those of healthy controls. The AUC for serum exosomal miR-17, miR-18, miR-19a and miR-92 was 0.750 (95%CI=0.626-0.874, sensitivity=84.7%, specificity=70.0%), 0.736 (95%CI=0.590-0.881, sensitivity=88.9%, specificity=65.0%), 0.700 (95%CI=0.562-0.838, sensitivity=62.5%, specificity=80.0%), 0.689 (95%CI=0.567-0.811, sensitivity=45.8%, specificity=90.0%), respectively. The AUC for the newly combined panel consisting of miR-17, miR-18, miR-19a and miR-92 was 0.808 (95%CI=0.680-0.937), with sensitivity of 90.3% and specificity of 70.0%, which showed much higher clinical diagnostic value for GC than any of the four alone or any pair. Besides, the AUC for the newly developed panel consisting of the two traditional tumor biomarkers including CEA (carcinoembryonic antigen) and CA19-9 (carbohydrate antigen 19-9) and the four miR-17-92 cluster members was 0.881 (95%CI, 0.765-0.998) with sensitivity of 91.7% and specificity of 90.0%, which showed the greatest powerful clinical diagnostic value for GC. Moreover, the elevated exosomal miR-17-92 expressions were closely correlated with tumor size, tumor depth, lymph node metastasis, distant metastasis and TNM stage of GC patients. In conclusion, our findings revealed that circulating exosomal miR-17-92 cluster may be used as a novel potential non-invasive biomarker to improve the diagnostic efficiency in GC.

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Overexpression of a novel oncogene Cadherin 6 correlates with tumor progression and poor prognosis in gastric cancer

10.21203/rs.3.rs-153934/v1 ◽

2021 ◽

Author(s):

Zongxian Zhao ◽

Shuliang Li ◽

Shilong Li ◽

Jun Wang ◽

Hai Lin ◽

...

Keyword(s):

Gastric Cancer ◽

Overall Survival ◽

Roc Curve ◽

Cox Regression ◽

Gene Set Enrichment Analysis ◽

Expression Level ◽

Diagnostic Efficiency ◽

Gastric Tissue ◽

Diagnosis And Prognosis ◽

T Classification

Abstract BackgroundGastric cancer (GC) is one of the most common and fatal cancers worldwide and effective biomarkers aids in GC management and prognosis. Hence, we explored the role and function of cadherin 6 (CDH6) in diagnosis and prognosis of gastric cancer. MethodsThe expression level of CDH6 in GC tissue and normal gastric tissue were analyzed using multiple public databases. Gene set enrichment analysis (GSEA) was performed using The Cancer Genome Atlas dataset (TCGA). The diagnostic efficiency of CDH6 expression in GC patients was determined through receiver operating characteristic (ROC) curve analysis. The associations between clinical variables and expression of CDH6 were evaluated statistically and the prognostic factors for overall survival were analyzed by univariate and multivariate Cox regression. Forty-four GC tissues, corresponding adjacent normal tissues (n=20), and detailed clinical information were collected from Tianjin Medical University General Hospital, CDH6 expression level was detected for further validation. ResultsCDH6 was upregulated in GC samples compared with normal gastric tissue, and GSEA identified the citrate cycle tricarboxylic (TCA) cycle, extracellular matrix (ECM) receptor interaction, glyoxylate and dicarboxylate metabolism oxidative phosphorylation, and pentose phosphate pathway as differentially enriched in GCs. According to the area under the ROC curve (AUC) (AUC=0.829 in TCGA and 0.966 in GSE54129), CDH6 had high diagnostic efficiency. Patients with high expression of CDH6 was associated with higher T classification and worse prognoses than those with low CDH6 expression in GC. Univariate and multivariate Cox regression analysis showed that CDH6 was an independent risk factor for overall survival (univariate: HR = 1.305, P = 0.002, multivariate: HR = 1.481, P < 0.001). ConclusionCDH6 was upregulated in GC and high CDH6 expression indicated higher T classification and worse prognoses. CDH6 could be a potentially independent molecular biomarker for diagnosis and prognosis of GC.

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circSMARCA5 Functions as a Diagnostic and Prognostic Biomarker for Gastric Cancer

Disease Markers ◽

10.1155/2019/2473652 ◽

2019 ◽

Vol 2019 ◽

pp. 1-11 ◽

Cited By ~ 6

Author(s):

Juan Cai ◽

Zhiqiang Chen ◽

Xueliang Zuo

Keyword(s):

Gastric Cancer ◽

Clinical Significance ◽

Survival Data ◽

Cox Regression ◽

Characteristic Curve ◽

Disease Free Survival ◽

Migration And Invasion ◽

Circular Rnas ◽

Functional Roles ◽

Potential Biomarker

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.

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Serum hsa_tsr016141 as a Kind of tRNA-Derived Fragments Is a Novel Biomarker in Gastric Cancer

Frontiers in Oncology ◽

10.3389/fonc.2021.679366 ◽

2021 ◽

Vol 11 ◽

Author(s):

Xinliang Gu ◽

Shuo Ma ◽

Bo Liang ◽

Shaoqing Ju

Keyword(s):

Gastric Cancer ◽

Sensitivity And Specificity ◽

Small Rnas ◽

Malignant Tumors ◽

Tumor Grade ◽

Expression Level ◽

Dynamic Monitoring ◽

Molecular Characteristics ◽

Diagnostic Efficiency ◽

Healthy Donors

BackgroundGastric cancer (GC) is one of the most common malignant tumors globally and the third leading cause of cancer-related death. Currently, the sensitivity and specificity of diagnostic markers for GC are low, so it is urgent to find new biomarkers with higher sensitivity and specificity. tRNA-derived small RNAs are a kind of small non-coding RNAs derived from tRNAs. It is abundant in cancer cells and body fluids. Our goal is to find the differentially expressed tRNA-derived small RNAs in GC to explore their potential as a GC biomarker.MethodsQuantitative real-time PCR was used to detect the expression level of hsa_tsr016141. The molecular characteristics of hsa_tsr016141 were verified by agarose gel electrophoresis, Sanger sequencing, Actinomycin D Assay, and Nuclear and Cytoplasmic RNA Separation Assay. The diagnostic efficiency of hsa_tsr016141 was analyzed through receiver operating characteristic.ResultsThe expression level of hsa_tsr016141 in GC tissues and serum was significantly increased. The serum expression level showed a gradient change between GC patients, gastritis patients, and healthy donors and was positively correlated with the degree of lymph node metastasis and tumor grade. ROC analysis showed that the serum expression level of hsa_tsr016141 could significantly distinguish GC patients from healthy donors or gastritis patients. Besides, the expression level of hsa_tsr016141 in GC patients decreased significantly after the operation (P<0.0001).ConclusionsSerum hsa_tsr016141 has good stability and specificity and can be used for dynamic monitoring of GC patients, suggesting that serum hsa_tsr016141 can be a novel biomarker for GC diagnosis and postoperative monitoring.

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Stmn1 up-regulates Cdx2 expression and participates in gastric intestinal metaplasia in vitro and in vivo: a randomized controlled trial

10.21203/rs.3.rs-42824/v1 ◽

2020 ◽

Author(s):

Xuan Chen ◽

Lizuan Chen ◽

Zeming Ren ◽

Yeling Tong ◽

Guanhai Dai ◽

...

Keyword(s):

Gastric Cancer ◽

Cell Line ◽

Precancerous Lesion ◽

Expression Level ◽

Pathological Examination ◽

Gastric Cell ◽

Potential Biomarker ◽

Im Model

Abstract BACKGROUND AND PURPOSE: Stmn1 is over-expressed in almost all pathological stages during gastric cancer development, such as chronic atrophic gastritis, dysplasia, and gastric cancer. IM is an important precancerous lesion of gastric cancer, however, whether Stmn1 was up-regulated or down-regulated in this stage is still unknown. We aimed to evaluate the expression level of Stmn1 in IM in vivo and its relationship with important gene of IM named Cdx2 in vitro.EXPERIMENTAL APPROACH: Wistar rats (n=12, sex in half) were gavaged with MNNG (167μg/ml) to induce IM model in stomach. After pathological examination with AB staining to confirm that the model was successful, relative expression level of Stmn1 was detected between normal group and model group using RT-qPCR. Human gastric cell line GES-1 was used to investigate whether Stmn1 influence expression level of IM essential gene Cdx2 by over-expressing or down-expressing experiments, RT-qPCR and western blot.KEY RESULTS: We have demonstrated that Stmn1 was up-regulated in IM model induced by MNNG in rats in vivo, and it could significantly up-regulate Cdx2 expression level in human gastric cell line GES-1 in vitro.CONCLUSIONS AND IMPLICATIONS: We demonstrated that Stmn1 was involved in IM in this model and it could up-regulating Cdx2 in human gastric cell line GES-1 in vitro. These results suggested that Stmn1 might be a potential biomarker or candidate treatment target of IM in stomach.

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Circulating serum exosomal miR-92a-3p as a novel biomarker for early diagnosis of gastric cancer

Future Oncology ◽

10.2217/fon-2020-0792 ◽

2021 ◽

Vol 17 (8) ◽

pp. 907-919

Author(s):

Xu Lu ◽

Jianxin Lu ◽

Siqi Wang ◽

Yu Zhang ◽

Ye Ding ◽

...

Keyword(s):

Gastric Cancer ◽

Early Diagnosis ◽

Malignant Tumors ◽

Area Under The Curve ◽

Tumor Biomarker ◽

Diagnostic Efficiency ◽

Node Metastasis ◽

Tumor Node Metastasis Stage ◽

Combined Detection ◽

Serum Exosomes

Gastric cancer (GC) is one of the common malignant tumors with high mortality. The abundance of miRNAs in serum exosomes has proved to have a high application value as a new noninvasive diagnostic method. The purpose of this study was to investigate whether serum exosomal miR-92a-3p could be used as a new biomarker for early diagnosis of GC and evaluate its clinical application value by detecting the expression of serum exosomal miR-92a-3p in 131 patients with primary GC and 122 healthy controls by real-time quantitative (qRT)-PCR. The results showed that the expression level of serum exosomal miR-92a-3p in GC patients was significantly lower than that in normal controls (p < 0.0001). In addition, the level was closely correlated with lymph node metastasis and tumor node metastasis stage of GC patients. The area under the curve for serum exosomal miR-92a-3p was 0.829, significantly higher than for other indicators. Furthermore, combined detection of serum exosomal miR-92a-3p, CEA and CA19-9 was more sensitive than any of the three alone or any pair. These results showed that serum exosomal miR-92a-3p could be used as a novel new tumor biomarker to improve diagnostic efficiency in GC.

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Diagnostic Value of Multi-Parameter MRI in Sub-Stage of T3 Rectal Cancer

Journal of Medical Imaging and Health Informatics ◽

10.1166/jmihi.2020.3213 ◽

2020 ◽

Vol 10 (11) ◽

pp. 2768-2772

Author(s):

Lei Xu ◽

Rui Shao ◽

Honglei Li ◽

Liang Wang

Keyword(s):

Rectal Cancer ◽

Characteristic Curve ◽

Diagnostic Value ◽

Youden Index ◽

Time Signal ◽

Diagnostic Efficiency ◽

Diagnostic Efficacy ◽

Diffusion Limited ◽

Morphological Index ◽

T3 Rectal Cancer

The paper aims to explore the diagnostic value of multi-parameter MRI in sub-stage of T3 rectal cancer. According to the results of clear pathological evaluation, 52 patients were divided into T3I and T3II groups according to the maximum mesorectum depth of tumor infiltration. The χ2 test was used to compare the differences of the overall morphology index, morphological index of the extramural strips, type of time-signal intensity curve (TIC), and the location index of DWI diffusion-limited distribution between the two groups. The independent sample t was used to test and compare the differences in semi-quantitative parameters of DCE between the two lesion groups. The pathological results were used as the dependent variables, the indicators mentioned above with statistical differences were used as the independent variables, and a Logistic regression model was established to construct joint parameters and evaluate its diagnostic efficacy. The differences in the circumferential diameter of lesions and morphological index of extramural strips (p < 0.01), and DWI diffusion restricted distribution index (p < 0.01) of the two groups were statistically significant. The difference in the DCE semiquantitative parameter early enhancement ratio (EER) (p < 0.01) between the two groups. The maximum Youden index of a newly-constructed parameter diagnosis combination: circumferential diameter of lesions + extramural strips + distribution locations of limited diffusion on DWI + EER was 0.73, the area under receiver operating characteristic curve(ROC) was 0.887 and the diagnostic sensitivity and specificity were 85.24% and 87.34%. By making full use of multi-parameter information, combined with morphological index of extramural strips, circumferential diameter of lesions, EER and distribution locations of the diffusion-limited of DWI as evaluation indexes, it can provide a high diagnostic efficiency for the sub-stage of T3 rectal cancer.

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Decreased Expression of Hsa_circ_00001649 in Gastric Cancer and Its Clinical Significance

Disease Markers ◽

10.1155/2017/4587698 ◽

2017 ◽

Vol 2017 ◽

pp. 1-6 ◽

Cited By ~ 43

Author(s):

Wen-han Li ◽

Yong-chun Song ◽

Hao Zhang ◽

Zhang-jian Zhou ◽

Xin Xie ◽

...

Keyword(s):

Gastric Cancer ◽

Expression Level ◽

Serum Samples ◽

Chain Reactions ◽

Normal Tissues ◽

Polymerase Chain Reactions ◽

Potential Biomarker ◽

Wide Range ◽

Pathological Differentiation ◽

Polymerase Chain

Background. It has been reported that circRNAs are differentially expressed in a wide range of cancers and could be used as a new biomarker for diagnosis. However, the correlation between circRNAs and gastric cancer (GC) it is still unclear. Materials and Methods. In this study, by using real-time quantitative reverse transcription-polymerase chain reactions (qRT-PCRs), we detected the expression level of hsa_circ_0001649 in tissue and serum samples from GC patients. Results. We found that hsa_circ_0001649 expression was significantly downregulated in GC tissue compared with their paired paracancerous histological normal tissues (PCHNTs) (P<0.01). We next analyzed the expression level of hsa_circ_0001649 in serum samples between preoperative and postoperative GC patients. We found that its level in serum was significantly upregulated after surgery (P<0.01). The area under the receiver operating characteristic (ROC) curve was 0.834. Moreover, the expression level of hsa_circ_0001649 was significantly correlated with pathological differentiation (P=0.039). Conclusion. Our test suggested that hsa_circ_0001649 was significantly downregulated in GC and may become a novel potential biomarker in the diagnosis of GC.

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Evaluation of the clinical usefulness of a chemiluminometric method for measuring creatine kinase MB

Clinical Chemistry ◽

10.1093/clinchem/36.10.1809 ◽

1990 ◽

Vol 36 (10) ◽

pp. 1809-1811 ◽

Cited By ~ 4

Author(s):

J R Pearson ◽

F Carrea

Keyword(s):

Creatine Kinase ◽

Predictive Value ◽

Characteristic Curve ◽

High Sensitivity ◽

High Specificity ◽

Receiver Operator Characteristic Curve ◽

Diagnostic Efficiency ◽

Predictive Values ◽

Creatine Kinase Mb ◽

Rule Out

Abstract The use of creatine kinase isoenzymes (CK-MB) in the diagnosis of acute myocardial infarction (AMI) is well established. We evaluated the use of a new chemiluminometric method (CK-Ciba) for measuring CK-MB by calculating its sensitivity, specificity, positive and negative predictive values, and diagnostic efficiency for diagnosing AMI. We tested 633 samples from 229 patients within 4 h of receipt. The patients were divided into four groups: (1) patients who had an AMI, (2) patients who had AMI ruled out, (3) patients who had CK-MB measured for reasons other than to rule out AMI, and (4) patients who had only one sample drawn. Only patients in Groups 1 and 2 were used in the study. AMI was diagnosed by a cardiologist. The prevalence of AMI in our population was 0.18. A receiver-operator characteristic curve was used to establish optimal values for identifying AMI with the CK-Ciba results: CK-MB greater than or equal to 10 micrograms/L and a CK-MB index of greater than or equal to 3.0 (micrograms of CK-MB per U of CK x 100). Using these values, we calculated a sensitivity of 1.00, specificity of 0.97, positive predictive value of 0.87, negative predictive value of 1.00, and a diagnostic efficiency of 0.97. We conclude that the CK-Ciba method has high sensitivity, high specificity, and good predictive values for CK-MB and is appropriate to use to rule out AMI.

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