scholarly journals Evaluation of the Diagnostic Potential of a Plasma Exosomal miRNAs Panel for Gastric Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Jiajia Yang ◽  
Xuan Li ◽  
Shuchun Wei ◽  
Lei Peng ◽  
Huaiming Sang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Roc Curves ◽  
Diagnostic Efficiency ◽  
Roc Curve Analysis ◽  
Kaplan Meier ◽  
Diagnostic Potential ◽  
Training Stage ◽  
Exosomal Mirnas ◽  
Tumor Phenotype

PurposeGastric cancer (GC) is often difficult to diagnose early in the disease and remains one of the most frequently occurring malignancies. This investigation looks at the diagnostic potential of a specific plasma exosomal miRNAs panel for GC.MethodsThis study analyzed 216 individual peripheral blood samples. 2 GEO datasets were analyzed and two miRNAs were selected - plasma exosomal miR-195-5p and miR-211-5p. Quantitative reverse-transcriptase PCR (qRT–PCR) was used to assess relative expressions and receiver operating characteristic (ROC) curve analysis was used to determine the diagnostic efficiency of miR-195-5p and miR-211-5p panel. The Kaplan-Meier method was used to assess the prognostic value of plasma exosomal miR-195-5p and miR-211-5p.ResultsGC patients possessed notably raised plasma levels of exosomal miR-195-5p and miR-211-5p. The area under ROC curves (AUCs) of miR-195-5p, miR-211-5p were 0.745, 0.798 in the screening phase and 0.762, 0.798 in the training stage respectively. GC was able to be diagnosed more accurately when both miRNAs were interpreted together (AUC=0.820 in the validation stage). Poorer prognosis was observed in GC patients who had plasma exosomal miR-195-5p and miR-211-5p of higher levels. In vitro experiments also confirmed that miR-195-5p and miR-211-5p is able to be transmitted between cells, and works to enhance tumor invasion, migration and proliferation while inhibiting cell apoptosis.ConclusionPlasma exosomal miR-195-5p and miR-211-5p may become potential biomarkers for GC diagnosis, and may be useful in predicting tumor phenotype.

scholarly journals A Novel Ferroptosis-Related Long Non-coding RNA Prognostic Risk Model for Gastric Cancer

2021 ◽  
Author(s):  
Shenglan Huang ◽  
Dan Li ◽  
Lingling Zhuang ◽  
Liying Sun ◽  
Jianbing Wu
Keyword(s):  
Gastric Cancer ◽  
Risk Score ◽  
Roc Curve ◽  
Cox Regression ◽  
Risk Group ◽  
Clinical Stage ◽  
Curve Analysis ◽  
Clinicopathological Features ◽  
Roc Curve Analysis ◽  
Kaplan Meier

Abstract Background：Gastric cancer (GC) is one of the most common malignant tumors with a poor prognosis. Ferroptosis is a novel and distinct type of non-apoptotic cell death that is closely associated with metabolism, redox biology, and tumor prognosis. Recently, ferroptosis-related long non-coding RNAs (lncRNAs) have received increasing attention in predicting cancer prognosis. Thus, we aimed to construct an ferroptosis-related lncRNAs signature for predicting the prognosis of patients with gastric cancer.Methods：We built an ferroptosis-related lncRNA risk signature by using Cox regression based on TCGA database. Kaplan-Meier survival analysis was conducted to compare the overall survival (OS) in different risk groups. Cox regression was performed to explore whether the signature could be used as an independent factor. A nomogram was built involving the risk score and clinicopathological features. Furthermore, we explored the biological functions and immune states in two groups.Results：Eight ferroptosis-related lncRNAs were obtained for constructing the prognosis model in gastric cancer. Kaplan–Meier curve analysis revealed that patients in the high-risk group had worse survival than those in the low-risk group. The survival outcome was also appropriate for subgroup analysis, including age, sex, grade, and clinical stage. Multivariate Cox regression analysis and receiver operating characteristic (ROC) curve analysis demonstrated that the risk score was an independent prognostic factor and superior to traditional clinicopathological features in predicting GC prognosis. Next, we established a nomogram according to clinical parameters (age, sex, grade, and clinical stage) and risk score. All the verified results, including ROC curve analysis, calibration curve, and decision curve analysis, demonstrated that the nomogram could accurately predict the survival of patients with gastric cancer. Gene set enrichment analysis revealed that these lncRNAs were mainly involved in cell adhesion, cancer pathways, and immune function regulation.Conclusion: We established a novel ferroptosis-related prognostic risk signature including eight lncRNAs and constructed a nomogram to predict the prognosis of gastric cancer patients, which may improve prognostic predictive accuracy and guide individualized treatment for patients with GC.

scholarly journals Identification of Circulating Exosomal miR-101 and miR-125b Panel Act as a Potential Biomarker for Hepatocellular Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Li Sun ◽  
Mu Xu ◽  
Guoying Zhang ◽  
Lin Dong ◽  
Jie Wu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Roc Curves ◽  
Fold Change ◽  
Diagnostic Utility ◽  
Roc Curve Analysis ◽  
Candidate Mirnas ◽  
Potential Biomarker ◽  
Exosomal Mirnas ◽  
Noninvasive Biomarker ◽  
New Diagnosis

Background. Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide with high mortality, and there is an urgent need of new diagnosis measures. This study is aimed at investigating whether circulating exosomal miRNAs could act as biomarkers for the diagnosis of HCC. Methods. A four-stage strategy was adopted in this study. Candidate miRNA was selected by comprehensive analysis of four GEO datasets and TCGA database. The expression of candidate miRNAs in serum exosomal samples were examined through qRT-PCR. The diagnostic utility of the final validated miRNAs was examined by receiver operating characteristic (ROC) curve analysis. Results. After synthetical analysis of four GEO datasets, six miRNAs were selected as candidates due to their higher differential fold change. miR-101 and miR-125b were selected as candidate miRNAs to further investigate their potential as biomarkers for HCC due to their differential fold change and their influence on overall survival based on the TCGA database. As a result, miR-101 and miR-125b expressions were remarkably downregulated in both tissues and serum exosomes of patients with HCC. The area under the ROC curves (AUCs) of circulating exosomal miR-101 and miR-125b were 0.894 (95% CI, 0.793–0.994) and 0.812 (95% CI, 0.675–0.950), respectively. The combination of the two miRNAs presented higher diagnostic utility for HCC ( AUC = 0.953 ). Conclusion. The exosomal miR-101 and miR-125b panel in the serum may act as a noninvasive biomarker for HCC detection.

scholarly journals CT Radiomics and Morphologic Characteristics for Predicting PD-L1 Expression on Tumour Cells and Tumour Infiltrating Lymphocytes in Gastric Cancer

2020 ◽  
Author(s):  
Xiangmei Qiao ◽  
Lin Li ◽  
Zhengliang Li ◽  
Changfeng Ji ◽  
Hui Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Clinical Decision Making ◽  
Roc Curves ◽  
Clinical Decision ◽  
Tumour Cells ◽  
Support Vector ◽  
Diagnostic Efficiency ◽  
Morphologic Characteristics ◽  
Tumour Infiltrating Lymphocytes ◽  
Infiltrating Lymphocytes

Abstract Background To explore CT radiomics and morphologic characteristics for predicting programmed cell death ligand 1 on tumour cells (PD-L1) and tumour infiltrating lymphocytes (PD-L1-TILs) status in gastric cancer (GC). Methods From March 2019 to October 2019, 101 patients identified with GCs who underwent surgery at our hospital were enrolled in this study retrospectively. Radiomic features were extracted from regions of interest manually drawn on venous CT images. Besides, 13 morphologic characteristics were evaluated. The signatures based on radiomics and morphologic characteristics were built using multiple classifiers (Support Vector Machine [SVM], Naive Bayes [NB], Decision Trees [DT], and Random Forest [RF]). Receiver operating characteristic (ROC) curve was performed to assess diagnostic efficiency. Results The adjacent adipose tissue (P = 0.009) and numerous radiomic features (all P < 0.05) differed significantly between GCs with different PD-L1 status. Six radiomic features showed significant differences between different PD-L1-TILs status (all P < 0.05). The highest areas under the ROC curves (AUCs) of signatures generated by classifiers were 0.807 (SVM) and 0.729 (NB) for the prediction of PD-L1 and PD-L1-TILs status, respectively. Conclusions It was promising to predict PD-L1 status in GCs noninvasively using CT radiomics combined with morphologic characteristics. It might help to improve clinical decision making with regard to immunotherapy. However, the prediction for PD-L1-TILs needs to be explored further.

scholarly journals CT radiomics and morphological characteristics for predicting PD-L1 expression on tumor cells and tumor infiltrating lymphocytes in gastric cancer

2021 ◽  
Author(s):  
Xiangmei Qiao ◽  
Mengying Xu ◽  
Song Liu ◽  
Zhengliang Li ◽  
Changfeng Ji ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Tumor Cells ◽  
Clinical Decision Making ◽  
Morphological Characteristics ◽  
Tumor Infiltrating Lymphocytes ◽  
Roc Curves ◽  
Clinical Decision ◽  
Support Vector ◽  
Diagnostic Efficiency ◽  
Infiltrating Lymphocytes

Abstract Purpose To explore CT radiomics and morphological characteristics for predicting programmed cell death ligand 1 on tumor cells (PD-L1) and tumor infiltrating lymphocytes (PD-L1-TILs) status in gastric cancer (GC).Methods From March 2019 to October 2019, 101 patients identified with GC who underwent surgery at our hospital were enrolled in this study retrospectively. Radiomic features were extracted from regions of interest manually drawn on venous CT images. Besides, 4 morphological characteristics were evaluated. The signatures based on radiomics and morphological characteristics were built using multiple classifiers (Support Vector Machine [SVM], Naive Bayes [NB], Decision Trees, and Random Forest). Receiver operating characteristic (ROC) curve was performed to assess diagnostic efficiency.Results The adjacent adipose tissue (p=0.009) and numerous radiomic features (all p<0.05) differed significantly between GCs with different PD-L1 status. Six radiomic features showed significant differences between different PD-L1-TILs status (all p<0.05). The highest areas under the ROC curves (AUCs) of signatures generated by classifiers were 0.807 (SVM) and 0.729 (NB) for the prediction of PD-L1 and PD-L1-TILs status, respectively.Conclusion It was promising to predict PD-L1 status in GCs noninvasively using CT radiomics combined with morphological characteristics. It might help to improve clinical decision making with regard to immunotherapy. However, the prediction for PD-L1-TILs needs to be explored further.

scholarly journals Correlation between LRP1B Mutations and Tumor Mutation Burden in Gastric Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Sizhe Hu ◽  
Xiaokang Zhao ◽  
Feng Qian ◽  
Cancan Jin ◽  
Kaishun Hou
Keyword(s):  
Gastric Cancer ◽  
Mutation Frequency ◽  
Density Lipoprotein ◽  
Roc Curves ◽  
Cancer Prognosis ◽  
Roc Curve Analysis ◽  
Mutation Status ◽  
Tumor Mutation Burden ◽  
Mutation Burden ◽  
The Relationship

Background. It has been shown that low-density lipoprotein receptor-related protein 1B (LRP1B) mutations correlate with tumor mutation burden (TMB) and prognosis in patients with melanoma and non-small-cell lung cancer, while the relationship between LRP1B mutations and TMB in gastric cancer needs further study. This study is aimed at exploring the relationship between LRP1B mutations and TMB in gastric cancer. Methods. Mutation frequency profiles of the genes in patients with gastric cancer in TCGA-STAD dataset were analyzed by bioinformatics analysis. The relationship among LRP1B mutations, TMB, and patient clinical features in gastric cancer was investigated by the chi-square test. The TMB prediction capacity based on LRP1B mutation status was evaluated by ROC curves. Results. LRP1B is one of the top 10 genes with high gene mutation frequency in gastric cancer. The mutation status of LRP1B in gastric cancer patients was significantly correlated with age and TP53 and MUC16 mutation status. The result of ROC curve analysis revealed that the mutation status of LRP1B could be considered as an indicator of the degree of TMB in patients with gastric cancer. Conclusion. This study presented the relationship between TMB and LRP1B mutations in gastric cancer, providing a novel perspective for gastric cancer prognosis and therapy.

scholarly journals XAGE-1b Promotes the Proliferation, Invasion and Metastasis of Gastric Cancer

2020 ◽  
Author(s):  
Hui Men ◽  
Zhi-wei Zhang ◽  
Gui-feng Lu ◽  
Shun Tan ◽  
Wen-Hui Hu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Malignant Tumors ◽  
Survival Curve ◽  
Biological Marker ◽  
Invasion And Metastasis ◽  
Treatment Target ◽  
Kaplan Meier ◽  
Proliferation And Invasion

Abstract Background X antigen family member 1B (XAGE-1b), a member of XAGE subfamily and GAGE family, is upregulated in some malignant tumors and has been associated with the proliferation, invasion and metastasis of tumors. However, the biological roles of XAGE-1b in gastric cancer (GC) still remain unclear. Methods We detected the expression of XAGE-1b in 60 paired fresh tissues of GC patients by real-time RT-PCR. Kaplan-Meier survival curve was explored to analyze 5-year survival time of GC patients. Function experiments were performed to estimate the role of XAGE-1b on the proliferation, invasion and metastasis of GC cells. Informatic analysis was applied to investigate the potential mechanisms. Results XAGE-1b was obviously upregulated in GC tissues. XAGE-1b was correlated significantly with poor prognosis of GC patients. XAGE-1b markedly promoted the proliferation and invasion in GC cell lines in vitro. Knockdown of XAGE-1b promoted the pulmonary metastatic ability in nude mice. Moreover, XAGE-1b was positively or negatively correlated with the expression of CLDN6 and CHGA, which regulated the progression of GC. Conclusions XAGE-1b could act as an oncogene in GC, which provides a potential biological marker or treatment target for GC.

MiR-485-5p as a potential biomarker and tumor suppressor in human colorectal cancer

2020 ◽  
Vol 14 (3) ◽  
pp. 239-248 ◽  
Author(s):  
Yuqin Pan ◽  
Jian Qin ◽  
Huiling Sun ◽  
Tao Xu ◽  
Shukui Wang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Suppressor ◽  
Cox Regression ◽  
Roc Curves ◽  
Functional Study ◽  
Kaplan Meier ◽  
Potential Biomarker ◽  
Polymerase Chain

Aim: To investigate the role of miR-485-5p in colorectal cancer (CRC). Methodology: The level of miR-485-5p in serum and cell lines were measured by quantitative real-time polymerase chain reaction, and analyzed the diagnostic and prognostic value. Additionally, the biological effect of miR-485-5p on CRC cells was also explored in vitro. Results: The receiver operating characteristic (ROC) curves analysis revealed that miR-485-5p was a diagnostic candidate. Kaplan-Meier analyses demonstrated that patients with low serum miR-485-5p had shorter overall survival. In addition, the result of cox regression model indicated that miR-485-5p was not an independent risk factor for progression. Functional study revealed that overexpression of miR-485-5p could inhibit CRC cell proliferation, invasion and facilitates cell apoptosis. Conclusion: Our study revealed that miR-485-5p was a tumor suppressor and it could serve as a potential prognostic biomarker in CRC.

scholarly journals Serum Exosomal miRNAs Are Associated with Active Pulmonary Tuberculosis

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Shamila D. Alipoor ◽  
Payam Tabarsi ◽  
Mohammad Varahram ◽  
Mehrnaz Movassaghi ◽  
Mehdi Kazempour Dizaji ◽  
...  
Keyword(s):  
Area Under The Curve ◽  
Roc Curve Analysis ◽  
Infection Level ◽  
Diagnostic Biomarkers ◽  
Active Pulmonary Tuberculosis ◽  
Diagnostic Potential ◽  
Exosomal Mirnas ◽  
Novel Biomarkers ◽  
Exosomal Mirna ◽  
Limited Accuracy

Introduction. Tuberculosis (TB) remains a major threat to human health. Due to the limited accuracy of the current TB diagnostic tests, it is critical to determine novel biomarkers for this disease. Circulating exosomes have been used as diagnostic biomarkers in various diseases. Objective of the Study. In this pilot study, we examined the expression of miRNAs as biomarker candidates for the diagnosis of TB infection. Methods. Serum-derived exosomes were isolated from TB patients and matched control subjects. The expression of miR-484, miR-425, and miR-96 was examined by RT-PCR methods. Results. The expression of miR-484, miR-425, and miR-96 were significantly increased in serum of TB patients which correlated with the TB infection level. A receiver operating characteristic (ROC) curve analysis showed the diagnostic potency of each individual serum exosomal miRNA with an area under the curve AUC=0.72 for miR-484 (p<0.05), 0.66 for miR-425 (p<0.05), and 0.62 for miR-96 (p<0.05). Conclusion. These results demonstrate that exosomal miRNAs have diagnostic potential in active tuberculosis. The diagnostic power may be improved when combined with conventional diagnostic markers.

scholarly journals HOXA13, Negatively Regulated by miR-139-5p, Decreases the Sensitivity of Gastric Cancer to 5-Fluorouracil Possibly by Targeting ABCC4

2021 ◽  
Vol 11 ◽  
Author(s):  
Zhengqian Chen ◽  
Zhiwei Qin ◽  
Lei Li ◽  
Qi Wo ◽  
Xia Chen
Keyword(s):  
Gastric Cancer ◽  
Underlying Mechanism ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Sequencing Analysis ◽  
Kaplan Meier ◽  
The Relationship ◽  
Kaplan Meier Plotter

PurposeChemoresistance remains a major challenge in the therapy of gastric cancer (GC). The homeobox (HOX) gene family has gained attention in carcinogenesis and chemoresistance. Here, this study aimed to explore the mechanism of HOXA13 in GC chemoresistance.MethodsQuantitative real-time PCR (qRT-PCR) and Western blot were used to evaluate the expression of HOXA13 in GC tissues. The Kaplan–Meier plotter database was mined for prognosis analysis of GC patients with different HOXA13 expression receiving 5-Fluorouracil (5-FU) therapy. The effects of HOXA13 on sensitivity of GC cells to 5-FU were investigated by Cell Counting Kit-8 (CCK-8), 5-Ethynyl-2’-deoxyuridine (EdU) incorporation, flow cytometry and experiment in vivo. RNA-Sequencing analysis was performed to explore the underlying mechanism of HOXA13-mediated 5-FU resistance in GC. Chromatin immunoprecipitation (ChIP) and rescue experiments were applied to determine the relationship between HOXA13 and ABCC4. Luciferase reporter assay was performed to assess interaction of miR-139-5p and HOXA13.ResultsHOXA13 was upregulated in GC and its high expression was associated with poor prognosis of GC patients with 5-FU treatment. Overexpression of HOXA13 impaired the inhibitory effects of 5-FU on GC cells proliferation in vitro and vivo, and knockdown of HOXA13 exacerbated 5-FU-induced GC cells apoptosis. Mechanistically, HOXA13, directly targeted by miR-139-5p in GC, might upregulate ABCC4 expression, thereby accentuating 5-FU resistance of GC cells.ConclusionOur study suggests that HOXA13 attenuates 5-FU sensitivity of GC possibly by upregulating ABCC4. Thus, targeting HOXA13 would provide a novel prospective into the potential therapeutic strategy for reversing chemoresistance.

scholarly journals Identification of dysregulated long noncoding RNA and associated mechanism in gastric cancer

2020 ◽  
Author(s):  
Liang Shao ◽  
Yanan Ming ◽  
Zhaoming Zhou
Keyword(s):  
Gastric Cancer ◽  
Noncoding Rna ◽  
Molecular Mechanisms ◽  
Cell Metabolism ◽  
Meta Analysis ◽  
Venn Diagram ◽  
Interactive Analysis ◽  
Kaplan Meier ◽  
Diagnostic Potential ◽  
Crucial Component

Abstract Gastric cancer (GC) is one of the most malignant epithelial tumors. The incidence of GC varies worldwide, and nearly half of the cases occur in Asian countries, especially in Japan and China. GC is the second leading cause of cancer-related deaths in the world, and current prognosis of advanced GC remains dismal despite improvements in diagnosis and therapy. Our current study aimed to identify significant long noncoding RNAs (lncRNAs) that could be used for prognosis and for the elucidation of associated molecular mechanisms. This study identified a substantial variety of reports using high-throughput lncRNA detection to investigate the expression of lncRNAs in GC development. However, the reported potentially diagnostic lncRNAs were unsuitable for meta-analysis, so we verified the expression of diagnostic lncRNAs and selected eight of them using Gene Expression Profiling Interactive Analysis (GEPIA). Next, we explored interactions of selected lncRNAs using Qiagen’s IPA system. We also identified differentially expressed genes (DEGs) of GC using the GEO2R online tool and datasets GSE52149, GSE19826, and GSE79973. To reveal genes that could be regulated by the selected lncRNA in GC, we used a Venn diagram and selected IGF2BP3 and FOLR1 as potential downstream targets of lncRNAs H19 and PVT1, respectively. Expression of IGF2BP3 and FOLR1 in GC validated by GEPIA was related to the worse prognosis for GC patients as shown by Kaplan Meier plots. Considering that IGF2BP3 promotes the expression of H19 and PEG10, down-regulation of their expression may improve the prognosis for GC patients, although at this time there is no evidence for direct involvement of IGF2BP3 in the regulation of these lncRNAs. The second DEG, FOLR1, is a crucial component of cell metabolism and DNA synthesis/repair required for cancer cell division. However, the role of FOLR1 in the etiology and progression of GC requires further study. In conclusion, using an integrated bioinformatic approach we identified eight significantly altered lncRNAs with diagnostic potential in GC patients. We also identified two axes - H19-IGF2BP3 and PVT1-FOLR1 – that may be related to the prognosis of GC and provide new insights into the etiology of GC and management of GC patients.

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