scholarly journals Ferroptosis-Related Long Non-Coding RNA Signature Predicts the Prognosis of Bladder Cancer

Author(s):  
Jian Hou ◽  
Zhenquan Lu ◽  
Xiaobao Cheng ◽  
Runan Dong ◽  
Yi Jiang ◽  
...  

Abstract Background: Ferroptosis is an iron-dependent programmed cell death modality that may have a tumor suppressor function. Therefore, regulating ferroptosis in tumor cells could serve as a novel therapeutic approach. This article focuses on ferroptosis-associated long non-coding RNAs (lncRNAs) and their potential application as a prognostic model for bladder cancer (BCa). Methods: We retrieved bladder cancer-related transcriptome information and clinical information from the TCGA database and ferroptosis-related gene sets from the FerrDb database. Minimum absolute shrinkage and selection operator regression and Cox regression models were used to identify and develop predictive models and validate the models' accuracy. Finally, we explore the inter-regulatory relationships between ferroptosis-related genes and immune cell infiltration, immune checkpoints, and m6A methylation genes. Results: Kaplan-Meier analyses revealed 11 differentially expressed lncRNAs associated with poor BCa prognosis. This signature (AUC = 0.720) could potentially be utilized to predict BCa prognosis. Our risk assessment model outperformed traditional clinicopathological features in predicting BCa prognosis. Additionally, GSEA revealed immune and tumor-related pathways in individuals in the low-risk group. TCGA showed that the p53 signaling pathway,ferroptosis,Kaposi sarcoma−associated herpesvirus infection,IL−17 signaling pathway,MicroRNAs in cancer,TNF signaling pathway,PI3K−Akt signaling pathway and HIF−1 signaling pathway were significantly different from those in the high-risk group. Immune checkpoints, such as PDCD-1 (PD-1), CTLA4, and LAG3, were also differentially expressed between the two risk groups. m6A methylation-related genes were likewise significantly differentially expressed between the two risk groups.Conclusion: A new ferroptosis-associated lncRNAs signature on the prognosis of BCa patients will provide new ideas for the treatment and management of BCa patients.

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11074
Author(s):  
Jin Duan ◽  
Youming Lei ◽  
Guoli Lv ◽  
Yinqiang Liu ◽  
Wei Zhao ◽  
...  

Background Lung adenocarcinoma (LUAD) is the most commonhistological lung cancer subtype, with an overall five-year survivalrate of only 17%. In this study, we aimed to identify autophagy-related genes (ARGs) and develop an LUAD prognostic signature. Methods In this study, we obtained ARGs from three databases and downloaded gene expression profiles from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. We used TCGA-LUAD (n = 490) for a training and testing dataset, and GSE50081 (n = 127) as the external validation dataset.The least absolute shrinkage and selection operator (LASSO) Cox and multivariate Cox regression models were used to generate an autophagy-related signature. We performed gene set enrichment analysis (GSEA) and immune cell analysis between the high- and low-risk groups. A nomogram was built to guide the individual treatment for LUAD patients. Results We identified a total of 83 differentially expressed ARGs (DEARGs) from the TCGA-LUAD dataset, including 33 upregulated DEARGs and 50 downregulated DEARGs, both with thresholds of adjusted P < 0.05 and |Fold change| > 1.5. Using LASSO and multivariate Cox regression analyses, we identified 10 ARGs that we used to build a prognostic signature with areas under the curve (AUCs) of 0.705, 0.715, and 0.778 at 1, 3, and 5 years, respectively. Using the risk score formula, the LUAD patients were divided into low- or high-risk groups. Our GSEA results suggested that the low-risk group were enriched in metabolism and immune-related pathways, while the high-risk group was involved in tumorigenesis and tumor progression pathways. Immune cell analysis revealed that, when compared to the high-risk group, the low-risk group had a lower cell fraction of M0- and M1- macrophages, and higher CD4 and PD-L1 expression levels. Conclusion Our identified robust signature may provide novel insight into underlying autophagy mechanisms as well as therapeutic strategies for LUAD treatment.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yingchun Liang ◽  
Fangdie Ye ◽  
Zhang Cheng ◽  
Yuxi Ou ◽  
Lujia Zou ◽  
...  

Abstract Background Muscle-invasive bladder cancer (MIBC) is one of the most important type of bladder cancer, with a high morbidity and mortality rate. Studies have found that long non-coding RNA (lncRNA) plays a key role in maintaining genomic instability. However, Identification of lncRNAs related to genomic instability (GIlncRNAs) and their clinical significance in cancers have not been extensively studied yet. Methods Here, we downloaded the lncRNA expression profiles, somatic mutation profiles and clinical related data in MIBC patients from The Cancer Genome Atlas (TCGA) database. A lncRNA computational framework was used to find differentially expressed GIlncRNAs. Multivariate Cox regression analysis was used to construct a genomic instability-related lncRNA signature (GIlncSig). Univariate and multivariate Cox analyses were used to assess the independent prognostic for the GIlncSig and other key clinical factors. Results We found 43 differentially expressed GIlncRNAs and constructed the GIlncSig with 6 GIlncRNAs in the training cohort. The patients were divided into two risk groups. The overall survival of patients in the high-risk group was lower than that in the low-risk group (P < 0.001), which were further verified in the testing cohort and the entire TCGA cohort. Univariate and multivariate Cox regression showed that the GIlncSig was an independent prognostic factor. In addition, the GIlncSig correlated with the genomic mutation rate of MIBC, indicating its potential as a measure of the degree of genomic instability. The GIlncSig was able to divide FGFR3 wild- and mutant-type patients into two risk groups, and effectively enhanced the prediction effect. Conclusion Our study introduced an important reference for further research on the role of GIlncRNAs, and provided prognostic indicators and potential biological therapy targets for MIBC.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Dongdong Zhou ◽  
Xiaoli Liu ◽  
Xinhui Wang ◽  
Fengna Yan ◽  
Peng Wang ◽  
...  

Abstract Background Alpha-fetoprotein-negative hepatocellular carcinoma (AFP-NHCC) (< 8.78 ng/mL) have special clinicopathologic characteristics and prognosis. The aim of this study was to apply a new method to establish and validate a new model for predicting the prognosis of patients with AFP-NHCC. Methods A total of 410 AFP-negative patients with clinical diagnosed with HCC following non-surgical therapy as a primary cohort; 148 patients with AFP-NHCC following non-surgical therapy as an independent validation cohort. In primary cohort, independent factors for overall survival (OS) by LASSO Cox regression were all contained into the nomogram1; by Forward Stepwise Cox regression were all contained into the nomogram2. Nomograms performance and discriminative power were assessed with concordance index (C-index) values, area under curve (AUC), Calibration curve and decision curve analyses (DCA). The results were validated in the validation cohort. Results The C-index of nomogram1was 0.708 (95%CI: 0.673–0.743), which was superior to nomogram2 (0.706) and traditional modes (0.606–0.629). The AUC of nomogram1 was 0.736 (95%CI: 0.690–0.778). In the validation cohort, the nomogram1 still gave good discrimination (C-index: 0.752, 95%CI: 0.691–0.813; AUC: 0.784, 95%CI: 0.709–0.847). The calibration curve for probability of OS showed good homogeneity between prediction by nomogram1 and actual observation. DCA demonstrated that nomogram1 was clinically useful. Moreover, patients were divided into three distinct risk groups for OS by the nomogram1: low-risk group, middle-risk group and high-risk group, respectively. Conclusions Novel nomogram based on LASSO Cox regression presents more accurate and useful prognostic prediction for patients with AFP-NHCC following non-surgical therapy. This model could help patients with AFP-NHCC following non-surgical therapy facilitate a personalized prognostic evaluation.


2021 ◽  
Author(s):  
Shaopei Ye ◽  
Wenbin Tang ◽  
Ke Huang

Abstract Background: Autophagy is a biological process to eliminate dysfunctional organelles, aggregates or even long-lived proteins. . Nevertheless, the potential function and prognostic values of autophagy in Wilms Tumor (WT) are complex and remain to be clarifed. Therefore, we proposed to systematically examine the roles of autophagy-associated genes (ARGs) in WT.Methods: Here, we obtained differentially expressed autophagy-related genes (ARGs) between healthy and Wilms tumor from Therapeutically Applicable Research To Generate Effective Treatments(TARGET) and The Cancer Genome Atlas (TCGA) database. The functionalities of the differentially expressed ARGs were analyzed using Gene Ontology. Then univariate COX regression analysis and multivariate COX regression analysis were performed to acquire nine autophagy genes related to WT patients’ survival. According to the risk score, the patients were divided into high-risk and low-risk groups. The Kaplan-Meier curve demonstrated that patients with a high-risk score tend to have a poor prognosis.Results: Eighteen DEARGs were identifed, and nine ARGs were fnally utilized to establish the FAGs based signature in the TCGA cohort. we found that patients in the high-risk group were associated with mutations in TP53. We further conducted CIBERSORT analysis, and found that the infiltration of Macrophage M1 was increased in the high-risk group. Finally, the expression levels of crucial ARGs were verifed by the experiment, which were consistent with our bioinformatics analysis.Conclusions: we emphasized the clinical significance of autophagy in WT, established a prediction system based on autophagy, and identified a promising therapeutic target of autophagy for WT.


2020 ◽  
Author(s):  
Dong dong Zhou ◽  
Xiao li Liu ◽  
Xin hui Wang ◽  
Feng na Yan ◽  
Peng Wang ◽  
...  

Abstract PurposeHepatocellular carcinoma (HCC) patients with alpha-fetoprotein (AFP)-negative (<8.78 ng/mL) have special clinicopathologic characteristics and prognosis. The aim of this study was to apply a new method to establish and validate a new model for predicting the prognosis of HCC patients with AFP-negative.Materials and MethodsA total of 410 AFP-negative patients with clinical diagnosed with HCC as a primary cohort; 148 AFP-negative HCC patients as an independent validation cohort. In primary cohort, independent factors for overall survival (OS) by LASSO Cox regression were all contained into the nomogram1; by univariate and multivariate Cox hazard analysis were all contained into the nomogram2. Nomograms performance and discriminative power were assessed with concordance index (C-index) values, area under curve (AUC), Calibration curve and decision curve analyses (DCA). The results were validated in the validation cohort.ResultsThe C-index of nomogram1was 0.708 (95%CI: 0.673-0.743), which was superior to nomogram2 (0.706) and traditional modes (0.606-0.629). The AUC of nomogram1 was 0.736 (95%CI: 0.690-0.778). In the validation cohort, the nomogram1 still gave good discrimination (C-index: 0.752, 95%CI: 0.691-0.813; AUC: 0.784, 95%CI: 0.709-0.847) and good calibration. The calibration curve for probability of OS showed good homogeneity between prediction by nomogram1 and actual observation. DCA demonstrated that nomogram1 was clinically useful. Moreover, patients were divided into three distinct risk groups for OS by the nomogram1: low-risk group, middle-risk group and high-risk group, respectively.ConclusionsNovel nomogram based on LASSO Cox regression presents more accurate and useful prognostic prediction for patients with AFP-negative HCC. This model could help AFP-negative HCC facilitate a personalized prognostic evaluation.


2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Jianfeng Zheng ◽  
Benben Cao ◽  
Xia Zhang ◽  
Zheng Niu ◽  
Jinyi Tong

Cervical cancer (CC) is a common gynecological malignancy for which prognostic and therapeutic biomarkers are urgently needed. The signature based on immune-related lncRNAs (IRLs) of CC has never been reported. This study is aimed at establishing an IRL signature for patients with CC. A cohort of 326 CC and 21 normal tissue samples with corresponding clinical information was included in this study. Twenty-eight IRLs were collected according to the Pearson correlation analysis between the immune score and lncRNA expression ( p < 0.01 ). Four IRLs (BZRAP1-AS1, EMX2OS, ZNF667-AS1, and CTC-429P9.1) with the most significant prognostic values ( p < 0.05 ) were identified which demonstrated an ability to stratify patients into the low-risk and high-risk groups by developing a risk score model. It was observed that patients in the low-risk group showed longer overall survival (OS) than those in the high-risk group in the training set, valid set, and total set. The area under the curve (AUC) of the receiver operating characteristic curve (ROC curve) for the four-IRL signature in predicting the one-, two-, and three-year survival rates was larger than 0.65. In addition, the low-risk and high-risk groups displayed different immune statuses in GSEA. These IRLs were also significantly correlated with immune cell infiltration. Our results showed that the IRL signature had a prognostic value for CC. Meanwhile, the specific mechanisms of the four IRLs in the development of CC were ascertained preliminarily.


2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Dakui Luo ◽  
Zezhi Shan ◽  
Qi Liu ◽  
Sanjun Cai ◽  
Qingguo Li ◽  
...  

A metabolic disorder is considered one of the hallmarks of cancer. Multiple differentially expressed metabolic genes have been identified in colon cancer (CC), and their biological functions and prognostic values have been well explored. The purpose of the present study was to establish a metabolic signature to optimize the prognostic prediction in CC. The related data were downloaded from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx) database, and Gene Expression Omnibus (GEO) combined with GSE39582 set, GSE17538 set, GSE33113 set, and GSE37892 set. The differentially expressed metabolic genes were selected for univariate Cox regression and lasso Cox regression analysis using TCGA and GTEx datasets. Finally, a seventeen-gene metabolic signature was developed to divide patients into a high-risk group and a low-risk group. Patients in the high-risk group presented poorer prognosis compared to the low-risk group in both TCGA and GEO datasets. Moreover, gene set enrichment analyses demonstrated multiple significantly enriched metabolism-related pathways. To sum up, our study described a novel seventeen-gene metabolic signature for prognostic prediction of colon cancer.


2019 ◽  
Vol 9 (3) ◽  
pp. 36 ◽  
Author(s):  
Bui My Hanh ◽  
Le Quang Cuong ◽  
Nguyen Truong Son ◽  
Duong Tuan Duc ◽  
Tran Tien Hung ◽  
...  

Venous thromboembolism (VTE) is a frequent preventable complication among surgical patients. Precise risk assessment is a necessary step for providing appropriate thromboprophylaxis and reducing mortality as well as morbidity caused by VTE. We carried out this work to define the rate of VTE postoperatively, following a Caprini score, and to determine VTE risk factors through a modified Caprini risk scoring system. This multicenter, observational, cohort study involved 2,790,027 patients who underwent surgery in four Vietnamese hospitals from 01/2017 to 12/2018. All patients who were evaluated before surgery by using a Caprini risk assessment model (RAM) and monitored within 90 days after surgery. The endpoint of the study was ultrasound-confirmed VTE. Our data showed that the 90-day postoperative VTE was found in 3068 patients. Most of VTE (46.97%) cases were found in the highest risk group (Caprini score > 5). A total of 37.19% were observed in the high risk group, while the rest (15.84%) were from low to moderate risk groups. The likelihood of occurring VTE was heightened 2.83 times for patients with a Caprini score of 3–4, 4.83 times for a Caprini score of 5–6, 8.84 times for a score of 7–8, and 11.42 times for a score of >8, comparing to ones with a score of 0 to 2 (all p values < 0.05). Thus, the frequency of postoperative VTE rises substantially, according to the advanced Caprini score. Further categorizing patients among the highest risk group need delivering more appropriate thromboprophylaxis.


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3285-3285
Author(s):  
Emilio Paolo Alessandrino ◽  
Luca Malcovati ◽  
Giorgio La Nasa ◽  
Paolo de Fabritiis ◽  
Massimo Bernardi ◽  
...  

Abstract This study investigated Thiotepa (TT) and Fludarabine (Fluda) as a preparative regimen for allogeneic peripheral stem cell transplantation in patients with myelodysplastic syndrome (MDS) or acute leukemia from MDS (MDS-AML) older than 50 or with comorbidities contraindicating standard conditioning. Patients were prepared with TT, given over 3 hours as an i.v. infusion at a dose of 10 mg/kg over two days (day -8 and day -7) and Fluda at the dose of 125 mg/m2 i.v. over five days ( from day -7 to day -3). Fresh or cryopreserved allogeneic peripheral stem cells were infused on day 0 or +1. Graft-versus-Host Disease (GvHD) prophylaxis consisted of cyclosporine A (CyA) at the dose of 1.5 mg/kg day as a continuous iv infusion from day -5 until engraftment. The CyA was then administered orally at the dose of 3 mg/kg twice a day. Doses were adjusted to maintain plasma level concentrations between 150–350 mg/dL. From day +60, in the absence of acute GvHD, the CyA was tapered down by 20% every 2 weeks until withdrawal. In addition, patients received methotrexate 10 mg/m2 on day +1, and 8 mg/m2 on days + 3, +6 and +11 after transplantation. At the time of transplantation, patients were classified in two risk groups (low vs high risk) according to IPSS score (low/intermediate-1 vs. intermediate-2/high) for MDS patients, and disease status (CR vs. not CR) for MDS-AML. Kaplan-Meier survival analysis was carried out to compare Overall Survival (OS), Transplant-Related Mortality (TRM) and probability of relapse. Fifty patients (29 males, 21 females) entered the study; the median age was 54 years (range 38–71). Sixteen MDS patients had a low/intermediate 1 score according to the International Prognostic Score System (IPSS), 16 had an intermediate 2/high IPSS score, 18 had MDS-AML. Thirty patients underwent transplantation as front-line therapy, 20 received one or more cycles of chemotherapy before transplant. Among the latter, nine with MDS-AML were in complete remission at the time of their transplant, while four were in a partial remission. The interval from diagnosis to transplantation ranged from 1 to 52 months (median value 11 months). Contraindications to a standard conditioning regimen were liver disease, hypertrophic cardiomyopathy secondary to hypertension or valvular stenosis, cardiac arrhythmia, diabetes mellitus, hypothyroidism, previous CNS bleeding, and a history of sepsis. All but one patient achieved engraftment, with full donor chimerism by day +30. Patients were followed up for a median time of 21 months (range 0.2–87). TRM at 1 and 2 years after transplantation was 25% and 33%; the 5-year probability of relapse was 27%. Twenty-six patients are alive in complete remission, and the 5-year OS is 50%. The 5-year OS was 73% and 28% in low- and high-risk patients respectively (p=0.002). TRM at 1 and 2 years after transplantation was 13% and 21% in the low-risk group and 39% and 45% in the high-risk group (p=0.046); the 5-year probability of relapse was 10% and 50% in the low- and high-risk group respectively (p=0.015). In a multivariate Cox regression, risk group retained a borderline significance (HR=2.6, p=0.07) when adjusted by age at transplantation (p=0.03) and interval from diagnosis to transplant (n.s.). The combination of Thiotepa and Fludarabine is an effective and well-tolerated conditioning regimen in patients with MDS or MDS-AML who are poor candidates for standard myeloablative transplantation, particularly in MDS patients with low/intermediate-1 IPSS score and MDS-AML patients in CR.


2021 ◽  
Vol 18 (6) ◽  
pp. 7743-7758
Author(s):  
Linlin Tan ◽  
◽  
Dingzhuo Cheng ◽  
Jianbo Wen ◽  
Kefeng Huang ◽  
...  

<abstract> <sec><title>Background</title><p>Hypoxia is a crucial factor in the development of esophageal cancer. The relationship between hypoxia and immune status in the esophageal cancer microenvironment is becoming increasingly important in clinical practice. This study aims to clarify and investigate the possible connection between immunotherapy and hypoxia in esophageal cancer.</p> </sec> <sec><title>Methods</title><p>The Cancer Genome Atlas databases are used to find two types of esophageal cancer cases. Cox regressions analyses are used to screen genes for hypoxia-related traits. After that, the genetic signature is validated by survival analysis and the construction of ROC curves. GSEA is used to compare differences in enrichment in the two groups and is followed by the CIBERSORT tool to investigate a potentially relevant correlation between immune cells and gene signatures.</p> </sec> <sec><title>Results</title><p>We found that the esophageal adenocarcinoma hypoxia model contains 3 genes (PGK1, PGM1, SLC2A3), and the esophageal squamous cell carcinoma hypoxia model contains 2 genes (EGFR, ATF3). The findings demonstrated that the survival rate of patients in the high-risk group is lower than in the lower-risk group. Furthermore, we find that three kinds of immune cells (memory activated CD4+ T cells, activated mast cells, and M2 macrophages) have a marked infiltration in the tissues of patients in the high-risk group. Moreover, we find that PD-L1 and CD244 are highly expressed in high-risk groups.</p> </sec> <sec><title>Conclusions</title><p>Our data demonstrate that oxygen deprivation is correlated with prognosis and the incidence of immune cell infiltration in patients with both types of esophageal cancer, which provides an immunological perspective for the development of personalized therapy.</p> </sec> </abstract>


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