scholarly journals Identification of a ferroptosis-related gene signature predictive model in colon cancer

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Ye Wang ◽  
Heng-bo Xia ◽  
Zhang-ming Chen ◽  
Lei Meng ◽  
A-man Xu
Keyword(s):  
Colon Cancer ◽  
Cox Regression ◽  
Risk Group ◽  
Expression Profiles ◽  
Risk Groups ◽  
High Risk Group ◽  
Low Risk ◽  
The Cancer Genome Atlas ◽  
Lasso Regression ◽  
Cox Regression Analysis

Abstract Background The prognosis of colon cancer (CC) is challenging to predict due to its highly heterogeneous nature. Ferroptosis, an iron-dependent form of cell death, has roles in various cancers; however, the correlation between ferroptosis-related genes (FRGs) and prognosis in CC remains unclear. Methods The expression profiles of FRGs and relevant clinical information were retrieved from the Cancer Genome Atlas (TCGA) database. Cox regression analysis and the least absolute shrinkage and selection operator (LASSO) regression model were performed to build a prognostic model in TCGA cohort. Results Ten FRGs, five of which had mutation rates ≥ 3%, were found to be related to the overall survival (OS) of patients with CC. Patients were divided into high- and low-risk groups based on the results of Cox regression and LASSO analysis. Patients in the low-risk group had a significantly longer survival time than patients in the high-risk group (P < 0.001). Enrichment analyses in different risk groups showed that the altered genes were associated with the extracellular matrix, fatty acid metabolism, and peroxisome. Age, risk score, T stage, N stage, and M stage were independent predictors of patient OS based on the results of Cox analysis. Finally, a nomogram was constructed to predict 1-, 3-, and 5-year OS of patients with CC based on the above five independent factors. Conclusion A novel FRG model can be used for prognostic prediction in CC and may be helpful for individualized treatment.

scholarly journals A prognostic five immune-related long noncoding RNA signature for patients with colon cancer

2020 ◽  
Author(s):  
Kankan Zhao ◽  
Mengchuan Wang ◽  
Houlong Kang ◽  
Aiguo Wu
Keyword(s):  
Colon Cancer ◽  
Regression Analysis ◽  
High Risk ◽  
Noncoding Rna ◽  
Cox Regression ◽  
Risk Group ◽  
High Risk Group ◽  
Low Risk ◽  
The Cancer Genome Atlas ◽  
Cox Regression Analysis

Abstract Background: Our study aimed to identify immune related long non-coding RNAs (LncRNAs) to serve as potential prognostic indicators and immune therapeutic targets in patients with colon cancer.Methods: The Cancer Genome Atlas (TCGA) and Molecular Signatures Databases (MSigDB) database were used to identify immune related lncRNAs in patients with colon cancer. The least absolute shrinkage and selection operator (LASSO) analysis, and multivariate Cox proportional hazards regression analysis were employed to screen prognostic lncRNAs and construct immune-related multi-lncRNA signature. We used time-dependent receiver operating characteristic curve to assess the performance of this signature in colon cancer by calculating the area under the curve (AUC). Univariate and multivariate Cox regression analysis were performed to verify the independence of the prognostic value of this signature in colon cancer.Results: Five immune related lncRNAs (AC025575.2, AL161729.4, ELFN1-AS1, LINC00513, MIR210HG) were found to be significantly associated with overall survival (OS) of patients with colon cancer. Then, we developed a five immune-related lncRNA signature. According to this signature, patients were ranked into a high risk group (n = 208) and a low risk group (n = 209). Kaplan-Meier curve and log-rank method showed that patients in high risk group had worse OS than patients in low risk group (P = 5.5644e-05). AUC for predicting 3 year survival and 5 year survival was 0.776 and 0.762 respectively, which indicated good performance of this signature. Finally, this five immune-related lncRNA signature was demonstrated to be independently associated with prognosis of patients with colon cancer.Conclusion: We developed a five immune-related lncRNA signature as a prognostic biomarker for patients with colon cancer.

scholarly journals An autophagy-related long non-coding RNA signature for patients with colorectal cancer

2021 ◽  
Author(s):  
Dongyan Zhao ◽  
Xizhen Sun ◽  
Sidan Long ◽  
Shukun Yao
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
High Risk ◽  
Cox Regression ◽  
Risk Group ◽  
Expression Profiles ◽  
High Risk Group ◽  
Low Risk ◽  
Gene Set Enrichment Analysis ◽  
Cox Regression Analysis

AbstractAimLong non-coding RNAs (lncRNAs) have been identified to regulate cancers by controlling the process of autophagy and by mediating the post-transcriptional and transcriptional regulation of autophagy-related genes. This study aimed to investigate the potential prognostic role of autophagy-associated lncRNAs in colorectal cancer (CRC) patients.MethodsLncRNA expression profiles and the corresponding clinical information of CRC patients were collected from The Cancer Genome Atlas (TCGA) database. Based on the TCGA dataset, autophagy-related lncRNAs were identified by Pearson correlation test. Univariate Cox regression analysis and the least absolute shrinkage and selection operator analysis (LASSO) Cox regression model were performed to construct the prognostic gene signature. Gene set enrichment analysis (GSEA) was used to further clarify the underlying molecular mechanisms.ResultsWe obtained 210 autophagy-related genes from the whole dataset and found 1187 lncRNAs that were correlated with the autophagy-related genes. Using Univariate and LASSO Cox regression analyses, eight lncRNAs were screened to establish an eight-lncRNA signature, based on which patients were divided into the low-risk and high-risk group. Patients’ overall survival was found to be significantly worse in the high-risk group compared to that in the low-risk group (log-rank p = 2.731E-06). ROC analysis showed that this signature had better prognostic accuracy than TNM stage, as indicated by the area under the curve. Furthermore, GSEA demonstrated that this signature was involved in many cancer-related pathways, including TGF-β, p53, mTOR and WNT signaling pathway.ConclusionsOur study constructed a novel signature from eight autophagy-related lncRNAs to predict the overall survival of CRC, which could assistant clinicians in making individualized treatment.

scholarly journals Development of Prognostic Indicator Based on Autophagy-Related lncRNA Analysis in Colon Adenocarcinoma

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Weige Zhou ◽  
Shijing Zhang ◽  
Hui-biao Li ◽  
Zheyou Cai ◽  
Shuting Tang ◽  
...  
Keyword(s):  
Risk Score ◽  
Noncoding Rna ◽  
Cox Regression ◽  
Risk Group ◽  
Expression Profiles ◽  
Colon Adenocarcinoma ◽  
High Risk Group ◽  
The Cancer Genome Atlas ◽  
Functional Enrichment ◽  
Lasso Regression

There were no systematic researches about autophagy-related long noncoding RNA (lncRNA) signatures to predict the survival of patients with colon adenocarcinoma. It was necessary to set up corresponding autophagy-related lncRNA signatures. The expression profiles of lncRNAs which contained 480 colon adenocarcinoma samples were obtained from The Cancer Genome Atlas (TCGA) database. The coexpression network of lncRNAs and autophagy-related genes was utilized to select autophagy-related lncRNAs. The lncRNAs were further screened using univariate Cox regression. In addition, Lasso regression and multivariate Cox regression were used to develop an autophagy-related lncRNA signature. A risk score based on the signature was established, and Cox regression was used to test whether it was an independent prognostic factor. The functional enrichment of autophagy-related lncRNAs was visualized using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. Ten prognostic autophagy-related lncRNAs (AC027307.2, AC068580.3, AL138756.1, CD27-AS1, EIF3J-DT, LINC01011, LINC01063, LINC02381, AC073896.3, and SNHG16) were identified to be significantly different, which made up an autophagy-related lncRNA signature. The signature divided patients with colon adenocarcinoma into the low-risk group and the high-risk group. A risk score based on the signature was a significantly independent factor for the patients with colon adenocarcinoma (HR=1.088, 95%CI=1.057−1.120; P<0.001). Additionally, the ten lncRNAs were significantly enriched in autophagy process, metabolism, and tumor classical pathways. In conclusion, the ten autophagy-related lncRNAs and their signature might be molecular biomarkers and therapeutic targets for the patients with colon adenocarcinoma.

scholarly journals Development and validation of Pyroptosis‑related lncRNAs prediction model for bladder cancer

2022 ◽  
Author(s):  
Thongher Lia ◽  
Yanxiang Shao ◽  
Parbatraj Regmi ◽  
Xiang Li
Keyword(s):  
Bladder Cancer ◽  
Regression Analysis ◽  
Cancer Patients ◽  
Risk Score ◽  
Cox Regression ◽  
Risk Group ◽  
Expression Profiles ◽  
Low Risk ◽  
The Cancer Genome Atlas ◽  
Cox Regression Analysis

Bladder cancer is one of the highly heterogeneous disorders accompanied by a poor prognosis. This study aimed to construct a model based on pyroptosis‑related lncRNA to evaluate the potential prognostic application in bladder cancer. The mRNA expression profiles of bladder cancer patients and corresponding clinical data were downloaded from the public database from The Cancer Genome Atlas (TCGA). Pyroptosis‑related lncRNAs were identified by utilizing a co-expression network of Pyroptosis‑related genes and lncRNAs. The lncRNA was further screened by univariate Cox regression analysis. Finally, 8 pyroptosis-related lncRNA markers were established using Lasso regression and multivariate Cox regression analysis. Patients were separated into high and low-risk groups based on the performance value of the median risk score. Patients in the high-risk group had significantly poorer overall survival (OS) than those in the low-risk group (p &lt; 0.001), and In multivariate Cox regression analysis, the risk score was an independent predictive factor of OS ( HR&gt;1, P&lt;0.01). The area under the curve (AUC) of the 3- and 5-year OS in the receiver operating characteristic (ROC) curve were 0.742 and 0.739 respectively. In conclusion, these 8 pyroptosis-related lncRNA and their markers may be potential molecular markers and therapeutic targets for bladder cancer patients.

scholarly journals The Value of Immune-Related Genes Signature in Osteosarcoma Based on Weighted Gene Co-expression Network Analysis

2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Xin Wang ◽  
Li Gan ◽  
Ju Ye ◽  
Mengjie Tang ◽  
Wei Liu
Keyword(s):  
Network Analysis ◽  
Cox Regression ◽  
Risk Group ◽  
Risk Groups ◽  
High Risk Group ◽  
Low Risk ◽  
Cox Regression Analysis ◽  
Potential Biomarker ◽  
Score Model ◽  
Immune Related Genes

Background. Osteosarcoma (OS) is a serious malignant tumor that is more common in adolescents or children under 20 years of age. This study is aimed at obtaining immune-related genes (IRGs) associated with the progression and prognosis of OS. Method. Expression profiling data and clinical data for OS were downloaded from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database. ESTIMATE calculates immune scores and stromal scores of samples and performs the prognostic analysis. Weighted gene coexpression network analysis (WGCNA) was used to find modules correlated with immune and stromal scores. Cox regression analysis and least absolute shrinkage and selection operator (LASSO) analysis were used to explore IRGs associated with OS prognosis and construct and validate a hazard score model. Finally, we verified the expression and function of EVI2B in OS. Results. WGCNA selected twenty-eight IRGs, 10 of which were associated with OS prognosis, and LASSO further obtained three key prognostic genes. A prognostic model of EVI2B was constructed, and according to the risk score model, patients in the high-risk group had a worse prognosis than those in the low-risk group, and the prognosis was statistically significant in the high- and low-risk groups. Receiver operating characteristic (ROC) curves were used to assess the prognostic model’s accuracy and externally validate the independent GSE21257 cohort. The results of immunohistochemical staining and qPCR showed that EVI2B was a tumor suppressor gene. The differential genes in the high- and low-risk groups were analyzed by enrichment analysis of GO and KEGG, indicating that the EVI2B model is associated with immune response. Conclusion. In this study, IRG EVI2B is closely related to OS’s prognosis and can be used as a potential biomarker for prognosis and treatment of OS.

scholarly journals Identification of the angiogenesis related genes for predicting prognosis of patients with gastric cancer

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Sheng Zheng ◽  
Zizhen Zhang ◽  
Ning Ding ◽  
Jiawei Sun ◽  
Yifeng Lin ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
High Efficiency ◽  
Cox Regression ◽  
Risk Group ◽  
The Cancer Genome Atlas ◽  
Differentially Expressed ◽  
Lasso Regression ◽  
Sequencing Data ◽  
Cox Regression Analysis

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.

scholarly journals Identification of prognostic gene signature associated with microenvironment of lung adenocarcinoma

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e8128 ◽  
Author(s):  
Cheng Yue ◽  
Hongtao Ma ◽  
Yubai Zhou
Keyword(s):  
High Risk ◽  
Lung Adenocarcinoma ◽  
Prognostic Model ◽  
Cox Regression ◽  
Risk Group ◽  
Expression Profiles ◽  
Gene Signature ◽  
Low Risk ◽  
Differentially Expressed ◽  
Lasso Regression

Background Lung cancer has the highest morbidity and mortality worldwide, and lung adenocarcinoma (LADC) is the most common pathological subtype. Accumulating evidence suggests the tumor microenvironment (TME) is correlated with the tumor progress and the patient’s outcome. As the major components of TME, the tumor-infiltrated immune cells and stromal cells have attracted more and more attention. In this study, differentially expressed immune and stromal signature genes were used to construct a TME-related prognostic model for predicting the outcomes of LADC patients. Methods The expression profiles of LADC samples with clinical information were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). The differentially expressed genes (DEGs) related to the TME of LADC were identified using TCGA dataset by Wilcoxon rank sum test. The prognostic effects of TME-related DEGs were analyzed using univariate Cox regression. Then, the least absolute shrinkage and selection operator (LASSO) regression was performed to reduce the overfit and the number of genes for further analysis. Next, the prognostic model was constructed by step multivariate Cox regression and risk score of each sample was calculated. Then, survival and Receiver Operating Characteristic (ROC) analyses were conducted to validate the model using TCGA and GEO datasets, respectively. The Kyoto Encyclopedia of Genes and Genomes analysis of gene signature was performed using Gene Set Enrichment Analysis (GSEA). Finally, the overall immune status, tumor purity and the expression profiles of HLA genes of high- and low-risk samples was further analyzed to reveal the potential mechanisms of prognostic effects of the model. Results A total of 93 TME-related DEGs were identified, of which 23 DEGs were up-regulated and 70 DEGs were down-regulated. The univariate cox analysis indicated that 23 DEGs has the prognostic effects, the hazard ratio ranged from 0.65 to 1.25 (p < 0.05). Then, seven genes were screened out from the 23 DEGs by LASSO regression method and were further analyzed by step multivariate Cox regression. Finally, a three-gene (ADAM12, Bruton Tyrosine Kinase (BTK), ERG) signature was constructed, and ADAM12, BTK can be used as independent prognostic factors. The three-gene signature well stratified the LADC patients in both training (TCGA) and testing (GEO) datasets as high-risk and low-risk groups, the 3-year area under curve (AUC) of ROC curves of three GEO sets were 0.718 (GSE3141), 0.646 (GSE30219) and 0.643 (GSE50081). The GSEA analysis indicated that highly expressed ADAM12, BTK, ERG mainly correlated with the activation of pathways involving in focal adhesion, immune regulation. The immune analysis indicated that the low-risk group has more immune activities and higher expression of HLA genes than that of the high-risk group. In sum, we identified and constructed a three TME-related DEGs signature, which could be used to predict the prognosis of LADC patients.

scholarly journals Weighted Gene Co-Expression Network Analysis Reveals a New Survival Model for Prognostic Prediction in Ewing Sarcoma

2021 ◽  
Author(s):  
Debao Li ◽  
Lei Wang ◽  
Guanghui Wang ◽  
Yaowen Yang ◽  
Weiyu Yang ◽  
...  
Keyword(s):  
Overall Survival ◽  
Network Analysis ◽  
Ewing Sarcoma ◽  
Prognostic Model ◽  
Risk Group ◽  
Expression Profiles ◽  
High Risk Group ◽  
Low Risk ◽  
Lasso Regression ◽  
Survival Status

Abstract Background: Ewing sarcoma (ES) is a malignant bone or soft-tissue cancer that mainly arises in children and young adults. However, the prognosis of Ewing sarcoma remains very poor, and there is no effective prediction method. The aim of our study was to identify a prognostic model for ES patients based on prognosis-associated mRNA expression profiles. Methods: The GSE17679 dataset was downloaded from the Gene Expression Omnibus (GEO) database. Differently expressed genes (DEGs) between ES and normal control were identified using R package “limma”. A weighted gene co-expression network analysis (WGCNA) was used to screen gene modules associated with recurrence/metastasis and survival status based on DEGs. Results: The prognostic model was constructed based on genes in MEbrown module, which was most associated with recurrence/metastasis and survival status, using Kaplan-Meier survival and lasso regression analysis. Sixteen genes were screened to construct the prognostic model. ES patients were grouped into high- and low-risk groups based on the median of risk score calculated for each of them. ES patients in high-risk group have worse survival than patients in low-risk group. The AUCs (Area under the ROC curve) for 1-year, 3-year, and 6-year overall survival were 0.903, 0.995, 0.953. Conclusions: Taken together, our research constructed a prognostic model which has excellent prediction performance for overall survival of ES patients.

scholarly journals A Novel Seventeen-Gene Metabolic Signature for Predicting Prognosis in Colon Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Dakui Luo ◽  
Zezhi Shan ◽  
Qi Liu ◽  
Sanjun Cai ◽  
Qingguo Li ◽  
...  
Keyword(s):  
Colon Cancer ◽  
High Risk ◽  
Cox Regression ◽  
Risk Group ◽  
High Risk Group ◽  
Low Risk ◽  
Differentially Expressed ◽  
Metabolic Signature ◽  
Metabolic Genes ◽  
Prognostic Prediction

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.

scholarly journals A novel signature of two long non-coding RNAs in BRCA mutant ovarian cancer to predict prognosis and efficiency of chemotherapy

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Yinglian Pan ◽  
Li Ping Jia ◽  
Yuzhu Liu ◽  
Yiyu Han ◽  
Qian Li ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
High Risk ◽  
Cox Regression ◽  
Risk Group ◽  
Gynecologic Cancer ◽  
High Risk Group ◽  
Low Risk ◽  
The Cancer Genome Atlas ◽  
Chemotherapy Treatment ◽  
Prognostic Signature

Abstract Background In this study we aimed to identify a prognostic signature in BRCA1/2 mutations to predict disease progression and the efficiency of chemotherapy ovarian cancer (OV), the second most common cause of death from gynecologic cancer in women worldwide. Methods Univariate Cox proportional-hazards and multivariate Cox regression analyses were used to identifying prognostic factors from data obtained from The Cancer Genome Atlas (TCGA) database. The area under the curve of the receiver operating characteristic curve was assessed, and the sensitivity and specificity of the prediction model were determined. Results A signature consisting of two long noncoding RNAs(lncRNAs), Z98885.2 and AC011601.1, was selected as the basis for classifying patients into high and low-risk groups (median survival: 7.2 years vs. 2.3 years). The three-year overall survival (OS) rates for the high- and low-risk group were approximately 38 and 100%, respectively. Chemotherapy treatment survival rates indicated that the high-risk group had significantly lower OS rates with adjuvant chemotherapy than the low-risk group. The one-, three-, and five-year OS were 100, 40, and 15% respectively in the high-risk group. The survival rate of the high-risk group declined rapidly after 2 years of OV chemotherapy treatment. Multivariate Cox regression associated with other traditional clinical factors showed that the 2-lncRNA model could be used as an independent OV prognostic factor. Analyses of data from the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) indicated that these signatures are pivotal to cancer development. Conclusion In conclusion, Z98885.2 and AC011601.1 comprise a novel prognostic signature for OV patients with BRCA1/2 mutations, and can be used to predict prognosis and the efficiency of chemotherapy.

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