scholarly journals High miR-324-5p expression predicts unfavorable prognosis of gastric cancer and facilitates tumor progression in tumor cells

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Zhong Zheng ◽  
Jun Li ◽  
Junyan An ◽  
Yikuan Feng ◽  
Lirong Wang
Keyword(s):  
Gastric Cancer ◽  
Cell Lines ◽  
Prognostic Value ◽  
Target Gene ◽  
Biological Function ◽  
Cox Regression ◽  
Survival Curve ◽  
Migration And Invasion ◽  
Loss Of Function ◽  
Cox Regression Analysis

Abstract Background Gastric cancer (GCa) is one of the six major malignancies in the world with low survival rate. Although there are advances in therapeutic approaches, the prognosis of patients with GCa remains not optimistic. Therefore, this study aimed to evaluate the prognostic value of miR-324-5p, as well as its functional role in GCa progression. Methods The expression of miR-324-5p in tumor tissues and cell lines was examined using real-time quantitative PCR. The prognostic value of miR-324-5p in patients with GCa was evaluated by Kaplan-Meier survival curve and Cox regression analysis. Gain- and loss-of-function experiments were performed to evaluate the biological function of miR-324-5p during the progression of GCa, and a target gene of miR-324-5p was proposed. Results The expression of miR-324-5p was up-regulated in GCa tissues and cell lines. Patients with high expression of miR-324-5p had more cases with positive lymph node metastasis, advanced TNM stage, and worse overall survival compared with patients with low expression. The elevated miR-324-5p was an independent prognostic indicator of GCa. In addition, the inhibition of miR-324-5p could suppress GCa cell proliferation, migration and invasion and promote cell apoptosis, and PTEN was demonstrated to serve as a direct target of miR-324-5p in GCa progression. Conclusion The present study indicates that miR-324-5p overexpression predicts poor prognosis in GCa patients, and the reduction of miR-324-5p can inhibit GCa biological processes. PTEN is a target gene of GCa, which may mediate the biological function of miR-324-5p in GCa progression.

scholarly journals MicroRNA-99b predicts clinical outcome of osteosarcoma and suppresses tumor cell proliferation, migration and invasion

2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Xin Shi ◽  
Xingfa Guan
Keyword(s):  
Cell Proliferation ◽  
Cell Lines ◽  
Prognostic Value ◽  
Cox Regression ◽  
Expression Profiles ◽  
Migration And Invasion ◽  
Aberrant Expression ◽  
Cox Regression Analysis ◽  
Normal Tissues

Abstract Background Osteosarcoma (OS) is a malignancy predominantly occurred in children and adolescents. Numerous microRNAs are involved in the pathogenesis of various cancers. This study aimed to investigate the expression profiles of miR-99b and its prognostic value in OS patients, and further analyze the biological function of miR-99b in the tumor progression by using OS cells. Methods Expression of miR-99b was measured using quantitative real-time PCR. Kaplan-Meier survival curves and Cox regression analysis were performed to evaluate the prognostic value of miR-99b. OS cell lines were used to investigate the effects of miR-99b on cell proliferation, migration and invasion. Results A significant decreased expression of miR-99b was observed in the OS tissues and cell lines respectively compared with the normal tissues and cells. Aberrant expression of miR-99b was associated with the patients’ metastasis and TNM stage, and could be used to predict the prognosis of OS. The expression of miR-99b was regulated in vitro by cell transfection, and we found that the overexpression of miR-99b led to suppressed cell proliferation, migration and invasion, whereas the knockdown of miR-99b resulted in the opposite results. Conclusions In one word, the aberrantly expressed miR-99b serves a prognostic biomarker for OS patients. OS cell proliferation, migration and invasion can be inhibited by the overexpression of miR-99b, suggesting that the methods to increase miR-99b expression may be novel therapeutic strategies in OS.

scholarly journals Distinctive Prognostic Value and Cellular Functions of Osteopontin Splice Variants in Human Gastric Cancer

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1820
Author(s):  
Chengcheng Hao ◽  
Yuxin Cui ◽  
Jane Lane ◽  
Shuqin Jia ◽  
Jiafu Ji ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Prognostic Value ◽  
Splice Variants ◽  
Tnm Staging ◽  
Migration And Invasion ◽  
Ros Production ◽  
Gastric Cancer Cells ◽  
Normal Tissues

Background: Osteopontin (OPN) splice variants are identified as predictors of tumour progression and therapeutic resistance in certain types of solid tumours. However, their roles in gastric cancer (GC) remain poorly characterized. The current study sought to assess the prognostic value of the three OPN splice variants (namely OPN-a, OPN-b, and OPN-c) in gastric cancer and their potential functions within gastric cancer cells. Methods: RNA extraction and reverse transcription were performed using our clinical cohort of gastric carcinomas and matched normal tissues (n = 324 matched pairs). Transcript levels were determined using real-time quantitative PCR. Three OPN splice variants overexpressed cell lines were created from the gastric cancer cell line HGC-27. Subsequently, biological functions, including cell growth, adhesion, migration, and invasion, were studied. The potential effects of OPN isoforms on cisplatin and 5-Fu were evaluated by detecting cellular reactive oxygen species (ROS) levels in the HGC-27-derived cell lines. Results: Compared with normal tissues, the expression levels of three splice variants were all elevated in gastric cancer tissues in an order of OPN-a > OPN-b > OPN-c. The OPN-a level significantly increased with increasing TNM staging and worse clinical outcome. There appeared to be a downregulation for OPN-c in increasing lymph node status (p < 0.05), increasing TNM staging, and poor differentiation. High levels of OPN-a and OPN-b were correlated with short overall survival and disease-free survival of gastric cancer patients. However, the low expression of OPN-c was significantly associated with a poor prognosis. Functional analyses further showed that ectopic expression of OPN-c suppressed in vitro proliferation, adhesiveness, migration, and invasion properties of HGC-27 cells, while the opposite role was seen for OPN-a. Cellular ROS detection indicated that OPN-a and OPN-c significantly promoted ROS production after treatment with 5-Fu comparing to OPN-vector, while only OPN-a markedly induced ROS production after treatment with cisplatin. Conclusion: Our results suggest that OPN splice variants have distinguished potential to predict the prognosis of gastric cancer. Three OPN variants exert distinctive functions in gastric cancer cells. Focusing on specific OPN isoforms could be a novel direction for developing diagnostic and therapeutic approaches in gastric cancer.

scholarly journals Efficacy of Postoperative FOLFOX Versus XELOX Chemotherapy for Gastric Cancer and Prognostic Value of Platelet–Lymphocyte Ratio in Patients Receiving XELOX

2020 ◽  
Vol 10 ◽  
Author(s):  
Xin Yin ◽  
Tianyi Fang ◽  
Yimin Wang ◽  
Chunfeng Li ◽  
Yufei Wang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Tumor Size ◽  
Prognostic Value ◽  
Cox Regression ◽  
Postoperative Chemotherapy ◽  
Chinese Patients ◽  
Cox Regression Analysis ◽  
Lymphocyte Ratio ◽  
Platelet Lymphocyte Ratio ◽  
Ptnm Stage

BackgroundSurgery combined with postoperative chemotherapy is an effective method for treating patients with gastric cancer (GC) in Asia. The important roles of systemic inflammatory response in chemotherapy have been gradually verified. The purpose of this study was to assess the difference in clinical effectiveness of FOLFOX (oxaliplatin + leucovorin + 5-fluorouracil) and XELOX (oxaliplatin + capecitabine), and the prognostic value of postoperative platelet–lymphocyte ratio (PLR) in the XELOX group.MethodsPatients who received radical gastrectomy combined with postoperative chemotherapy between 2004 and 2014 were consecutively selected into the FOLFOX and XELOX groups. Group bias was reduced through propensity score matching, which resulted in 278 patients in each group. Cut-off values of systemic immune inflammation (SII) score and PLR were obtained by receiver operating characteristic curve. Kaplan–Meier and Log-rank tests were used to analyze overall survival. The chi-square test was used to analyze the association between clinical characteristics and inflammatory indexes. Univariate and multivariate analyses based on Cox regression analysis showed independent risk factors for prognosis. The nomogram was made by R studio.ResultsPatients receiving XELOX postoperative chemotherapy had better survival than those receiving FOLFOX (P &lt; 0.001), especially for stage III GC (P = 0.002). Preoperative SII was an independent risk factor for prognosis in the FOLFOX group, and PLR of the second postoperative chemotherapy regimen in the XELOX group, combined with tumor size and pTNM stage, could construct a nomogram for evaluating recurrence and prognosis.ConclusionXELOX is better than FOLFOX for treatment of GC in Chinese patients, and a nomogram constructed by PLR, tumor size and pTNM stage can predict recurrence and prognosis.

scholarly journals Construction on of a Ferroptosis-Related lncRNA-Based Model to Improve the Prognostic Evaluation of Gastric Cancer Patients Based on Bioinformatics

2021 ◽  
Vol 12 ◽  
Author(s):  
Jiahui Pan ◽  
Xinyue Zhang ◽  
Xuedong Fang ◽  
Zhuoyuan Xin
Keyword(s):  
Gastric Cancer ◽  
Cancer Patients ◽  
Roc Curve ◽  
Cox Regression ◽  
Risk Group ◽  
Survival Curve ◽  
Curve Analysis ◽  
Roc Curve Analysis ◽  
Cox Regression Analysis ◽  
Gastric Cancer Patients

BackgroundGastric cancer is one of the most serious gastrointestinal malignancies with bad prognosis. Ferroptosis is an iron-dependent form of programmed cell death, which may affect the prognosis of gastric cancer patients. Long non-coding RNAs (lncRNAs) can affect the prognosis of cancer through regulating the ferroptosis process, which could be potential overall survival (OS) prediction factors for gastric cancer.MethodsFerroptosis-related lncRNA expression profiles and the clinicopathological and OS information were collected from The Cancer Genome Atlas (TCGA) and the FerrDb database. The differentially expressed ferroptosis-related lncRNAs were screened with the DESeq2 method. Through co-expression analysis and functional annotation, we then identified the associations between ferroptosis-related lncRNAs and the OS rates for gastric cancer patients. Using Cox regression analysis with the least absolute shrinkage and selection operator (LASSO) algorithm, we constructed a prognostic model based on 17 ferroptosis-related lncRNAs. We also evaluated the prognostic power of this model using Kaplan–Meier (K-M) survival curve analysis, receiver operating characteristic (ROC) curve analysis, and decision curve analysis (DCA).ResultsA ferroptosis-related “lncRNA–mRNA” co-expression network was constructed. Functional annotation revealed that the FOXO and HIF-1 signaling pathways were dysregulated, which might control the prognosis of gastric cancer patients. Then, a ferroptosis-related gastric cancer prognostic signature model including 17 lncRNAs was constructed. Based on the RiskScore calculated using this model, the patients were divided into a High-Risk group and a low-risk group. The K-M survival curve analysis revealed that the higher the RiskScore, the worse is the obtained prognosis. The ROC curve analysis showed that the area under the ROC curve (AUC) of our model is 0.751, which was better than those of other published models. The multivariate Cox regression analysis results showed that the lncRNA signature is an independent risk factor for the OS rates. Finally, using nomogram and DCA, we also observed a preferable clinical practicality potential for prognosis prediction of gastric cancer patients.ConclusionOur prognostic signature model based on 17 ferroptosis-related lncRNAs may improve the overall survival prediction in gastric cancer.

scholarly journals Enhanced expression of miR-889 forecasts an unfavorable prognosis and facilitates cell progression in hepatocellular carcinoma

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
He Wang ◽  
Huiwen Wang ◽  
Wenyu Cui ◽  
Qiao Zhang ◽  
Jing Li ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Cell Lines ◽  
Cox Regression ◽  
Malignant Tumors ◽  
Prognostic Significance ◽  
High Expression ◽  
Migration And Invasion ◽  
Pcr Analysis ◽  
Cox Regression Analysis

Abstract Background As a new type of molecular marker, microRNAs (miRNAs) can be used for early diagnosis and prognosis prediction of malignant tumors, and has broad clinical application prospects. This paper mainly studies the important role of miR-889 in the occurrence and development of hepatocellular carcinoma and the prognostic significance of miR-889 in hepatocellular carcinoma. Methods Quantitative real-time PCR analysis detected the expression levels of miR-889 in hepatocellular carcinoma tissues and cell lines. Kaplan-Meier curve and Cox regression analysis were used to explore the prognostic significance of miR-889 in hepatocellular carcinoma. The CCK-8 and Transwell assays assay were used to assess cell proliferation, migration, and invasion abilities ability. Results The expression of miR-889 in hepatocellular carcinoma tissues was significantly higher than that in adjacent tissues. Overexpression of miR-889 was significantly associated with TNM stage, hepatitis B virus infection, and cirrhosis. Patients with high miR-889 expression had shorter overall survival than those with low miR-889 expression. And functional studies in two hepatocellular carcinoma cell lines have shown that overexpression of miR-889 significantly promoted cell proliferation, migration, and invasion in vitro. Conclusions Overall, miR-889 was upregulated in hepatocellular carcinoma tissues and cell lines, and overexpression of miR-889 promoted cell proliferation, migration, and invasion in hepatocellular carcinoma cells. Based on our findings, high expression of miR-889 may promote the progression of hepatocellular carcinoma, and high expression of miR-889 is also forecasted for an unfavorable prognosis in hepatocellular carcinoma.

scholarly journals THOTTIP is Associated with Prognosis of Lung Cancer in the Chinese Population

2020 ◽  
Author(s):  
Yue Zhao ◽  
Xiangjun Kong ◽  
Hongbing Wang
Keyword(s):  
Lung Cancer ◽  
Prognostic Value ◽  
Cox Regression ◽  
Survival Curve ◽  
Expression Patterns ◽  
Rank Test ◽  
Chi Square ◽  
Cox Regression Analysis ◽  
Lung Cancer Patients ◽  
High Level

Abstract Background: Lung cancer is a prevent malignancy with high mortality. Long noncoding RNAs (lncRNAs) have been reported to play important roles in tumorigenesis. The purpose of this study was to explore the prognostic value of lncRNA HOTTIP in lung cancer.Methods: The expression of HOTTIP in lung cancer tissues was measured by quantitative real-time PCR (qRT-PCR). Chi-square test was applied to assess the correlation of HOTTIP with clinicopathological features. Overall survival curve was built by Kaplan-Meier method with log rank test. Cox regression analysis was used to explore the prognostic value of HOTTIP in lung cancer.Results: The expression of HOTTIP was significantly increased in lung cancer samples compared with paired noncancerous samples (P<0.001). Moreover, its expression patterns were correlated with lymph node metastasis (P=0.039) and TNM stage (P=0.007). Survival curve demonstrated that lung cancer patients with high level of HOTTIP had poor survival rate (log-rank P=0.011). HOTTIP might be an independent prognostic factor for lung cancer (HR=1.916, 95%CI=1.133-3.238, P=0.015).Conclusions: HOTTIP is up-regulated in lung cancer, and associated with aggressive tumor progression. HOTTIP may be a potential prognostic biomarker for lung cancer.

scholarly journals MiR-455-3p downregulation facilitates cell proliferation and invasion and predicts poor prognosis of osteosarcoma

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Xijun Yi ◽  
Yafei Wang ◽  
Shijie Xu
Keyword(s):  
Cell Proliferation ◽  
Cell Lines ◽  
Cox Regression ◽  
Clinical Stage ◽  
Prognostic Indicator ◽  
Cell Counting ◽  
Migration And Invasion ◽  
Cox Regression Analysis ◽  
Cox Analysis

Abstract Background Osteosarcoma (OS) is one of the most primary malignant bone tumors, mainly attracting children and young adults. The microRNAs are mentioned to play vital roles in many cancers, including OS. The purpose of this study was to explore the expression and function of miR-455-3p in OS and predict the potential effects in clinical diagnosis and prognosis. Method We conducted quantitative real-time PCR to assess the expression of miR-455-3p in OS tissues and cell lines. The Cell Counting Kit-8 assay, Transwell assay, and flow cytometry were performed to assess the ability of miR-455-3p on cell proliferation, migration, invasion, and apoptosis. Kaplan–Meier curve and Cox regression analysis were used to demonstrate the survival outcome. Results This study revealed that the expression of miR-455-3p was decreased in OS tissues and cell lines. The dysregulation of miR-455-3p was in association with tumor size, distant metastasis, and clinical stage. Patients with high miR-455-3p expression had a satisfying survival rate. Multivariate Cox analysis indicated that miR-455-3p was a promising prognostic indicator. Expression of miR-455-3p could inhibit the proliferation, migration, and invasion, and facilitate apoptosis of OS cells in vitro. Conclusion These results indicated the miR-455-3p was a potential clinical therapeutic target and prognostic biomarker by suppressing the proliferation, migration, and invasion, as well as enhancing cell apoptosis.

scholarly journals miR-3196 acts as a Tumor Suppressor and Predicts Survival Outcomes in Patients With Gastric Cancer

2020 ◽  
Vol 19 ◽  
pp. 153303382092342
Author(s):  
Guo Chen ◽  
Jinliang Wan ◽  
Zhenbo Wang ◽  
Lei Li ◽  
Hongying Jia ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Target Gene ◽  
Cox Regression ◽  
Migration And Invasion ◽  
Chain Reaction ◽  
Gastric Cancer Cells ◽  
Kaplan Meier ◽  
Polymerase Chain ◽  
Cancer Tissues

Background: Gastric cancer is one of the most common malignancies worldwide with high mortality. Therefore, identifying cancer-related biomarkers for predicting prognosis and progression of gastric cancer is essential. This study aimed to investigate the clinical value and functional role of microRNA-3196 in gastric cancer. Methods: The relative expression levels of microRNA-3196 in gastric cancer tissues and adjacent normal tissues were detected by quantitative reverse transcription-polymerase chain reaction. In this study, quantitative reverse transcription-polymerase chain reaction, cell proliferation assay, and Transwell migration and invasion assays were performed to explore microRNA-3196 expression level and its effects on cell proliferation, migration, and invasion in gastric cancer cells. The Kaplan-Meier method and multivariate Cox regression analyses were used to explore the prognostic significance of microRNA-3196 in gastric cancer. Dual-luciferase report assay was performed to validate the potential target gene regulated by microRNA-3196 in gastric cancer. Results: The expression of microRNA-3196 was downregulated in gastric cancer tissues and cell lines. Downregulation of microRNA-3196 was associated with lymph node metastasis and Tumor Node Metastasis (TNM) stage. The Kaplan-Meier curve analysis indicated that patients with low expression of microRNA-3196 had a poor prognosis, and the Cox regression analysis results showed microRNA-3196 expression was an independent prognostic factor of gastric cancer. Moreover, overexpression of microRNA-3196 inhibited cell proliferation, migration, and invasion, while knockdown of microRNA-3196 promoted these cellular behaviors in AGS and MKN45 cells. OTX1 may be a potential target gene regulated by microRNA-3196 in gastric cancer. Conclusions: These results suggested that microRNA-3196 might not only a tumor suppressor in gastric cancer cells by modulating OTX1 but also might be an independent prognostic biomarker and therapeutic target of gastric cancer.

scholarly journals Exosomal miR-590-5p in Serum as a Biomarker for the Diagnosis and Prognosis of Gastric Cancer

2021 ◽  
Vol 8 ◽  
Author(s):  
Guo-Dian Zheng ◽  
Zhi-Yuan Xu ◽  
Can Hu ◽  
Hang Lv ◽  
Hua-Xia Xie ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cox Regression ◽  
Quantitative Polymerase Chain Reaction ◽  
Characteristic Curve ◽  
Clinical Stage ◽  
Expression Level ◽  
Migration And Invasion ◽  
Serum Samples ◽  
Ki 67 ◽  
Cox Regression Analysis

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 &lt; 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 &lt; 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 &lt; 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.

scholarly journals The Novel Role of LINC01235 in Metastasis of Gastric Cancer Cells by Inducing Epithelial-mesenchymal Transition

2020 ◽  
Author(s):  
Cheng Zhang ◽  
Yu Liang ◽  
Chun-Dong Zhang ◽  
Dong-Qiu Dai
Keyword(s):  
Gastric Cancer ◽  
Cox Regression ◽  
Migration And Invasion ◽  
Rna Seq ◽  
Pcr Assay ◽  
Cox Regression Analysis ◽  
Qrt Pcr ◽  
Overall Survival Analysis

Abstract BackgroundLncRNAs play a vital role in the tumorigenesis of gastric cancer (GC). The present study aims to explore the role of LINC01235 in clinical significance, prognostic prediction and GC metastasis.MethodsWe identified differentially expressed lncRNAs using stomach adenocarcinoma RNA-Seq data from The Cancer Genome Atlas (TCGA). The expression of LINC01235 in GC cell lines and tissues were confirmed by qRT-PCR assay. The overall survival analysis and univariate/ multivariate Cox regression analysis were performed to explore the prognostic value of LINC01235. In vitro assays were utilized to assess the effect of LINC01235 in cell migration and invasion. Western blotting measured the expression of EMT-induced proteins.ResultsThis study determined that LINC01235 expression has a higher fold changes by analyzing TCGA RNA-Seq data. qRT-PCR assay confirmed that LINC01235 is significantly over-expressed in GC cells and tissues. Additionally, the overall survival analysis showed that patients with a higher LINC01235 expression had a poorer prognosis than those with a lower LINC01235 expression. Univariate Cox regression analysis indicated that high LINC01235 expression is positively correlated with poor prognosis. Moreover, LINC01235 was an independent poor prognostic marker for GC in multivariate Cox analysis. In vitro assays suggested that LINC01235 knockdown suppresses GC cell migration and invasion. GSEA revealed that high LINC01235 expression is strongly enriched in EMT pathway. Western blotting results revealed that LINC01235 silencing decreases the expression of EMT-induced proteins.ConclusionLINC01235 could promote GC cell metastasis via EMT and function as a prognostic biomarker.

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