scholarly journals Integrated Analysis of lncRNA-Associated ceRNA Network Identifies Two lncRNA Signatures as a Prognostic Biomarker in Gastric Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Shuyan Zhang ◽  
Shanshan Li ◽  
Jian-Lin Guo ◽  
Ningyi Li ◽  
Cai-Ning Zhang ◽  
...  

Background. Gastric cancer (GC) is a malignant tumour that originates in the gastric mucosal epithelium and is associated with high mortality rates worldwide. Long noncoding RNAs (lncRNAs) have been identified to play an important role in the development of various tumours, including GC. Yet, lncRNA biomarkers in a competing endogenous RNA network (ceRNA network) that are used to predict survival prognosis remain lacking. The aim of this study was to construct a ceRNA network and identify the lncRNA signature as prognostic factors for survival prediction. Methods. The lncRNAs with overall survival significance were used to construct the ceRNA network. Function enrichment, protein-protein interaction, and cluster analysis were performed for dysregulated mRNAs. Multivariate Cox proportional hazards regression was performed to screen the potential prognostic lncRNAs. RT-qPCR was used to measure the relative expression levels of lncRNAs in cell lines. CCK8 assay was used to assess the proliferation of GC cells transfected with sh-lncRNAs. Results. Differentially expressed genes were identified including 585 lncRNAs, 144 miRNAs, and 2794 mRNAs. The ceRNA network was constructed using 35 DElncRNAs associated with overall survival of GC patients. Functional analysis revealed that these dysregulated mRNAs were enriched in cancer-related pathways, including TGF-beta, Rap 1, calcium, and the cGMP-PKG signalling pathway. A multivariate Cox regression analysis and cumulative risk score suggested that two of those lncRNAs (LINC01644 and LINC01697) had significant prognostic value. Furthermore, the results indicate that LINC01644 and LINC01697 were upregulated in GC cells. Knockdown of LINC01644 or LINC01697 suppressed the proliferation of GC cells. Conclusions. The authors identified 2-lncRNA signature in ceRNA regulatory network as prognostic biomarkers for the prediction of GC patient survival and revealed that silencing LINC01644 or LINC01697 inhibited the proliferation of GC cells.

2020 ◽  
Vol 27 (4) ◽  
pp. 599-607
Author(s):  
Konstantinos Stavroulakis ◽  
Asimakis Gkremoutis ◽  
Matthias Borowski ◽  
Giovanni Torsello ◽  
Dittmar Böckler ◽  
...  

Purpose: To report the outcomes of bypass grafting (BG) vs endovascular therapy (EVT) in patients with non-dialysis-dependent chronic kidney disease (CKD) and chronic limb-threatening ischemia (CLTI). Materials and Methods: The CRITISCH Registry is a prospective, national, interdisciplinary, multicenter registry evaluating the current practice of all available treatment options in 1200 consecutive CLTI patients. For the purposes of this analysis, only the 337 patients with non-dialysis-dependent CKD treated by either BG (n=86; median 78 years, 48 men) or EVT (n=251; median age 80 years, 135 men) were analyzed. The primary composite outcome was amputation-free survival (AFS); secondary outcomes were overall survival (OS) and amputation-free time (AFT). All outcomes were evaluated in Cox proportional hazards models; the results are reported as the hazard ratio (HR) and 95% confidence interval (CI). Results: The Cox regression analysis revealed a significantly greater hazard of amputation or death after BG (HR 1.78, 95% CI 1.05 to 3.03, p=0.028). The models for AFT and overall survival also suggested a higher hazard for BG, but the differences were not significant (AFT: HR 1.66, 95% CI 0.78 to 3.53, p=0.188; OS: HR 1.41, 95% CI 0.80 to 2.47, p=0.348). The absence of runoff vessels (HR 1.73, 95% CI 1.15 to 2.60, p=0.008) was associated with a decreased AFS. The likelihood of amputation was higher in male patients (HR 2.21, 95% CI 1.10 to 4.45, p=0.027) and was associated with a lack of runoff vessels (HR 1.95, 95% CI 0.96 to 3.95, p=0.065) and myocardial infarction (HR 3.74, 95% CI 1.23 to 11.35, p=0.020). Death was more likely in patients without runoff vessels (HR 1.76, 95% CI 1.11 to 2.80, p=0.016) and those with a higher risk score (HR 1.73, 95% CI 1.03 to 2.91, p=0.038). Conclusion: This analysis suggested that BG was associated with poorer AFS than EVT in patients with non-dialysis-dependent CKD and CLTI. Male sex, previous myocardial infarction, and the absence of runoff vessels were additionally identified as predictors of poorer outcomes.


2021 ◽  
Vol 19 (4) ◽  
pp. 403-410
Author(s):  
Héctor G. van den Boorn ◽  
Ameen Abu-Hanna ◽  
Nadia Haj Mohammad ◽  
Maarten C.C.M. Hulshof ◽  
Suzanne S. Gisbertz ◽  
...  

Background: Personalized prediction of treatment outcomes can aid patients with cancer when deciding on treatment options. Existing prediction models for esophageal and gastric cancer, however, have mostly been developed for survival prediction after surgery (ie, when treatment has already been completed). Furthermore, prediction models for patients with metastatic cancer are scarce. The aim of this study was to develop prediction models of overall survival at diagnosis for patients with potentially curable and metastatic esophageal and gastric cancer (the SOURCE study). Methods: Data from 13,080 patients with esophageal or gastric cancer diagnosed in 2015 through 2018 were retrieved from the prospective Netherlands Cancer Registry. Four Cox proportional hazards regression models were created for patients with potentially curable and metastatic esophageal or gastric cancer. Predictors, including treatment type, were selected using the Akaike information criterion. The models were validated with temporal cross-validation on their C-index and calibration. Results: The validated model’s C-index was 0.78 for potentially curable gastric cancer and 0.80 for potentially curable esophageal cancer. For the metastatic models, the c-indices were 0.72 and 0.73 for esophageal and gastric cancer, respectively. The 95% confidence interval of the calibration intercepts and slopes contain the values 0 and 1, respectively. Conclusions: The SOURCE prediction models show fair to good c-indices and an overall good calibration. The models are the first in esophageal and gastric cancer to predict survival at diagnosis for a variety of treatments. Future research is needed to demonstrate their value for shared decision-making in clinical practice.


2021 ◽  
Author(s):  
Ting Jiang ◽  
Zixiang Ye ◽  
TianYu Shao ◽  
YiYang Luo ◽  
BinBin Wang

Abstract Backgrounds: Angiosarcoma (AS) is a kind of highly aggressive cancer with high occurrence and mortality rates. This study aimed to establish a comprehensive and validated prognostic nomogram with various clinical indicators in patients with AS.Methods: Data of patients with AS diagnosed after surgery between 2010 and 2015 was retrieved from the Surveillance Epidemiology and End Results (SEER) database. Univariate and multivariate Cox proportional hazards regression analysis were performed to identify the independent prognostic factors associated with survival to construct the predictive nomogram of 3- and 5-year overall survival (OS) and cancer-specific survival (CSS) rates. Concordance-index(C-index), calibration plots and receiver operating characteristic (ROC) curves were applied to evaluate the predictive ability of the nomograms. The further decision curve analysis (DCA) was drawn to confirm the clinical usefulness of the nomograms.Results: 323 patients in total with AS were divided into the training group (N =226) and the validation group (N = 97). After the multivariate Cox regression analysis, gender, age, AJCC stage group 7th ed, T, N and M stage 7th ed, histologic grade and primary site were statistically identified as independent factors with OS and CSS (P<0.05). The C-index of the nomograms for OS and CCS in the training cohort was 0.760 (95%CI: 0.674–0.847) and 0.793 (95%CI: 0.687–0.898), meanwhile, the C-index of those in the validation cohort was 0.790 (95%CI: 0.725–0.855) and 0.888 (95%CI: 0.799–0.976) respectively. The results of calibration plots and ROC curve showed the nomograms qualified to measure the risk and prognosis. DCA exhibited good clinical utility of nomograms.Conclusion: Our study has developed novel and practical nomograms for predicting prognosis in patients with AS contributing to cancer management.


2021 ◽  
Author(s):  
Jia Miao ◽  
Haibin Wei ◽  
Jianxin Cui ◽  
Xinpeng Chen ◽  
Qi Zhang ◽  
...  

Abstract Background: bladder cancer (BCa) is a common malignancy in the urinary system. But the hematogenous metastatic pattern of it was poorly explored. The aim of this study was to provide a better understanding of the prognosis of the different distant metastatic pattern from stage IV BCa patients and support for making a suitable clinical decision.Methods: The Surveillance, Epidemiology and End Result database (SEER) provided data for this study include BCa from 2010 to 2015. Kaplan–Meier method was used to evaluate the survival prognosis of patients of metastatic BCa. Cox proportional hazards regression model was utilized to analyzed risk factors. All statistical tests were two-sided.Results: At the time of diagnosis, a total of 6808 eligible patients at stage IV were extracted from SEER database. Patients who suffered metastasis to either one of the four sites occupied 25.31% (1723/6808) of BCa. Bone was the most common distant metastatic site of BCa (1225 cases), and brain metastases had the worst prognosis whose mean survival was 6.282 months. The results of univariate survival analysis presented that diagnostic age, race, gender, primary site surgery, tumor size, T stage, N stage, primary tumor site, histology, marital status and metastatic number were independent prognostic factors affecting overall survival (OS) (P<0.05). On multivariable Cox regression, squamous cell carcinoma was an independent risk factor affecting the overall survival (P < 0.05). The nomogram model was constructed to show the 1-, 3- and 5-year survival rates of patients.Conclusion: In analysis of single metastatic sites, patients with brain metastasis had the worst overall survival and lung metastasis had the best outcomes than other three distant metastases. Knowledge of these differences in metastatic patterns is helpful for clinicians to make better pre-treatment evaluation and clinical decisions.


2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 181-181 ◽  
Author(s):  
David Frazier Jarrard ◽  
Yu-Hui Chen ◽  
Glenn Liu ◽  
Michael Anthony Carducci ◽  
Mario A. Eisenberger ◽  
...  

181 Background: To evaluate whether metformin (Met) a widely-used, nontoxic oral antidiabetic drug with putative anticancer properties leads to improvements in prostate cancer (PC) outcomes in the CHAARTED trial. Methods: In the CHAARTED database where metformin use at baseline was recorded prospectively, we identified patients with metastatic PC who underwent either ADT alone or ADT and docetaxel (D) chemotherapy. Cox proportional hazards models were used to determine the effect of Metformin on outcomes. Results: A total of 788 patients (median age, 63 y) had complete data after randomization. Comparison of ADT+D+Met (n = 39) to ADT+D (n = 357) and ADT+Met (n = 29) to ADT alone (n = 363) revealed similar clinicopathologic characteristics. Cause of death was PC in 13(81%) of ADT+D+Met, 72(85%) ADT+D, 9(82%) ADT+Met and 105(84%) ADT alone groups. See table for PC outcomes and overall survival by metformin use. Cox regression analysis for overall survival stratified by stratification factors at randomization demonstrates Met use was associated with a trend for worse overall survival (HR 1.47 95%CI: [0.95,2.26], p = 0.08) with adjustment for treatment arm and prior local therapy. In contrast, ADT+D use (HR 0.62; 95%CI: [0.47,0.81]) and prior local therapy with surgery or radiation (HR 0.56; 95% CI: [0.38, 0.82]) were associated with improved survival. Conclusions: In this study, baseline metformin did not improve PC outcomes. Partial support and drug supply by Sanofi. Clinical trial information: NCT00309985. [Table: see text]


2020 ◽  
Author(s):  
Xin Xu ◽  
Youliang Wu ◽  
Mingliang Wang ◽  
Yida Lu ◽  
Xiaodong Wang ◽  
...  

Abstract Background: Gastric cancer (GC) is one of the most fatal malignant tumors with a high mortality rate. Male sex has been proven as an independent risk factor for GC. This study aimed to identify immune-related genes (IRGs) for the prognosis of male GC.Method: RNA sequencing and clinical data were obtained from The Cancer Genome Atlas (TCGA) database. Differentially expressed IRGs between male GC and normal tissues were identified by integrated bioinformatics analysis. Univariate and multivariate Cox regression analysis were applied to screen survival-associated IRGs. Then, GC patients were separated into high- and low-risk groups based on the median risk score. Furthermore, a nomogram was constructed based on the TCGA dataset. The prognostic value of the risk signature model was evaluated by Kaplan-Meier curve, receiver operating characteristic (ROC), Harrell’s concordance index and calibration curves. In addition, the gene expression dataset from Gene Expression Omnibus (GEO) was also downloaded for external validation. The relative proportions of 22 types of infiltrating immune cells in each male GC sample were evaluated using CIBERSORT.Results: A total of 276 differentially expressed IRGs were screened, including 189 up-regulated and 87 down-regulated genes. Subsequently, a seven-IRGs signature (LCN12, CCL21, RNASE2, CGB5, NRG4, AGTR1 and NPR3) was identified and showed a significant association with the overall survival (OS) of male GC patients. Survival analysis indicated that patients with high-risk group exhibited a poor clinical outcome. The result of multivariate analysis revealed that the risk score was an independent prognostic factor. The established nomogram could be used to evaluate the prognosis of individual male GC patients. Further analysis showed that the prognostic model had an excellent predictive performance in both TCGA and validated cohorts. Besides, the result of tumor-infiltrating immune cell analysis indicated that the seven-IRGs signature could reflect the status of the tumor immune microenvironment.Conclusions: Our study developed a novel seven-IRGs risk signature for individualized survival prediction of male GC patients.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Sheng Zheng ◽  
Zizhen Zhang ◽  
Ning Ding ◽  
Jiawei Sun ◽  
Yifeng Lin ◽  
...  

Abstract Introduction Angiogenesis is a key factor in promoting tumor growth, invasion and metastasis. In this study we aimed to investigate the prognostic value of angiogenesis-related genes (ARGs) in gastric cancer (GC). Methods mRNA sequencing data with clinical information of GC were downloaded from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. The differentially expressed ARGs between normal and tumor tissues were analyzed by limma package, and then prognosis‑associated genes were screened using Cox regression analysis. Nine angiogenesis genes were identified as crucially related to the overall survival (OS) of patients through least absolute shrinkage and selection operator (LASSO) regression. The prognostic model and corresponding nomograms were establish based on 9 ARGs and verified in in both TCGA and GEO GC cohorts respectively. Results Eighty-five differentially expressed ARGs and their enriched pathways were confirmed. Significant enrichment analysis revealed that ARGs-related signaling pathway genes were highly related to tumor angiogenesis development. Kaplan–Meier analysis revealed that patients in the high-risk group had worse OS rates compared with the low-risk group in training cohort and validation cohort. In addition, RS had a good prognostic effect on GC patients with different clinical features, especially those with advanced GC. Besides, the calibration curves verified fine concordance between the nomogram prediction model and actual observation. Conclusions We developed a nine gene signature related to the angiogenesis that can predict overall survival for GC. It’s assumed to be a valuable prognosis model with high efficiency, providing new perspectives in targeted therapy.


2021 ◽  
Author(s):  
Xinyu Wang ◽  
Zhuangsen Chen ◽  
Fan Yang ◽  
Xiaohan Ding ◽  
Changchun Cao ◽  
...  

Abstract Background: Research on the relationship between Creatinine to Body Weight Ratios (Cre/BW ratios) and the prevalence of diabetes is still lacking. The aim of this study was to investigate the potential association between Cre/BW ratios and incident of diabetes in Chinese adults.Methods: This retrospective study was conducted in 199,526 patients from Rich Healthcare Group in China from 2010 to 2016. The participants were divided into quartiles of the Cre/BW ratios. Multivariate multiple imputation and dummy variables were used to handle missing values. Cox proportional-hazards regression was used to investigate the association of Cre/BW and diabetes. Generalized additive models(GAM) were used to identify non-linear relationships.Results: Of all participants,after handling missing values and adjustment for potential confounders, the multivariate Cox regression analysis results showed that Cre/BW ratios was inversely associated with diabetes risk( HR: 0.268; 95% CI:0.229 to 0.314, P < 0.00001).For men, the hazard ratios(HRs) of incident diabetes was 0.255(95%CI: 0.212-0.307);and for women HR= 0.297 (95%CI: 0.218-0.406).Moreover, sensitivity analysis confirmed the stability of the results. Furthermore, GAM revealed a saturation effect on the independent association between Cre/BW and incident of diabetes.Conclusions: This study demonstrated that increased Cre/BW is negatively correlated with incident of diabetes in Chinese for the first time. And we found that the relationship between Cre/BW and incident of diabetes was non-linear.


2021 ◽  
Author(s):  
Dan Bai ◽  
Huhu Feng ◽  
Jiajun Yang ◽  
Haitao Shi ◽  
Fanpu Ji ◽  
...  

Abstract Early diagnosis and prognosis rely on the successful identification of biomarkers and understanding the mechanisms. Through pan-cancer analysis amongst three types of gastrointestinal tumors, we constructed competitive endogenous RNA (ceRNA) networks, differentially expressed set of genes were distinguished, validated, and analyzed, their relevance to survival elucidated with immune infiltration profiles. Shared genes in esophageal, gastric and colon cancers were found significantly enriched in the processes of cell cycle, cell differentiation, DNA replication, synaptic transmission, the cyclic guanosine monophosphate protein-dependent protein kinase (cGMP-PKG) signaling pathway, and the glutamate receptor and other functions. Principal component analysis of the ceRNA network suggested the expression patterns of identified genes. Using Cox regression analysis of mRNAs, miRNAs and lncRNAs in the ceRNA network, genes including hsa-mir-196b, hsa-mir-584, PPP1R12B, SYNM, PDE2A, ALDH6A1 and MIR22HG were found significantly survival-related. Receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA) showed that the identified genes were not related to the survival in thyroid nor breast cancers, but effective for the prognosis of gastrointestinal tumors. These results could provide new theoretical and experimental clues, unravel the mechanisms, assisting molecular diagnosis and prognosis of gastrointestinal tumors.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16659-e16659
Author(s):  
Sunyoung S. Lee ◽  
Yehia I. Mohamed ◽  
Aliya Qayyum ◽  
Manal Hassan ◽  
Lianchun Xiao ◽  
...  

e16659 Background: Child-Turcotte-Pugh (CTP) score is widely used in the assessment of prognosis of HCC and CTP-A is the standard criterion for active therapy and clinical trials entry. Recently, ALBI and insulin-like growth factor-1 (IGF)-CTP scores have been reported to improve survival prediction over CTP score. However, comparative studies to compare both scores and to integrate IGF into Albi score are lacking. Methods: After institutional board approval, data and samples were prospectively collected. 299 HCC patients who had data to generate both IGF-CPG and Albi index were used. The ALBI index, and IGF score were calculated, Cox proportional hazards models were fitted to evaluation the association between overall survival (OS) and CTP, IGF-CTP, Albi and IGF, albumin, bilirubin. Harrell’s Concordance index (C-index) was calculated to evaluate the ability of the three score system to predict overall survival. And the U-statistics was used to compare the performance of prediction of OS between the score system. Results: OS association with CTP, IGF-CTP and Albi was performed (Table). IGF-CTP B was associated with a higher risk of death than A (HR = 1.6087, 95% CI: 1.2039, 2.1497, p = 0.0013), ALBI grade 2 was also associated with a higher risk of death than 1 (HR = 2.2817, 95% CI: 1.7255, 3.0172, p < 0.0001). IGF-1(analyzed as categorical variable) was independently associated with OS after adjusting for the effects of ALBI grade. Which showed IGF-1 ≤26 was significantly associated with poor OS, P = 0.001. Conclusions: Although ALBI grade and IGF-CTP score in this analysis had similar prognostic values in most cases, their benefits might be heterogenous in some specific conditions. We looked into corporation of IGF-1 into ALBI grade, IGF score with cutoff ≤26 which clearly refined OS prediction and better OS stratification of ALBI-grade.


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