scholarly journals A six-gene-based signature for breast cancer radiotherapy sensitivity prediction

2020 ◽  
Author(s):  
Xing Chen ◽  
Junjie Zheng ◽  
Min ling Zhuo ◽  
Ailong Zhang ◽  
Zhenhui You
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Regression Analysis ◽  
Cox Regression ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Cox Regression Analysis ◽  
Breast Cancer Radiotherapy

Abstract Background: Breast cancer (BRCA) represents the most common malignancy among women worldwide that with high mortality. Radiotherapy is a prevalent therapeutic for BRCA that with heterogeneous effectiveness among patients. Methods: we proposed to develop a gene expression-based signature for BRCA radiotherapy sensitivity prediction. Gene expression profiles of BRCA samples from the Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) were obtained and used as training and independent testing dataset, respectively. Differential expression genes (DEGs) in BRCA tumor samples compared with their paracancerous samples in the training set were identified by using edgeR Bioconductor package followed by dimensionality reduction through autoencoder method and univariate Cox regression analysis to screen genes among DEGs that with significant prognosis significance in patients that were previously treated with radiation. LASSO Cox regression method was applied to screen optimal genes for constructing radiotherapy sensitivity prediction signature. Results: 603 DEGs were obtained in BRCA tumor samples, and seven out of which were retained after univariate cox regression analysis. LASSO Cox regression analysis finally remained six genes based on which the radiotherapy sensitivity prediction model was constructed. The signature was proved to be robust in both training and independent testing sets and an independent marker for BRCA radiotherapy sensitivity prediction. Conclusions: this study should be helpful for BRCA patients’ therapeutics selection and clinical decision.

scholarly journals A six-gene-based signature for breast cancer radiotherapy sensitivity estimation

2020 ◽  
Vol 40 (12) ◽  
Author(s):  
Xing Chen ◽  
Junjie Zheng ◽  
Min ling Zhuo ◽  
Ailong Zhang ◽  
Zhenhui You
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Immune Checkpoint ◽  
Cox Regression ◽  
Expression Profiles ◽  
Cancer Genome ◽  
Mrna Levels ◽  
Cox Regression Analysis ◽  
Sensitivity Estimation ◽  
Checkpoint Receptors

Abstract Breast cancer (BRCA) represents the most common malignancy among women worldwide with high mortality. Radiotherapy is a prevalent therapeutic for BRCA that with heterogeneous effectiveness among patients. Here, we proposed to develop a gene expression-based signature for BRCA radiotherapy sensitivity estimation. Gene expression profiles of BRCA samples from the Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) were obtained and used as training and independent testing dataset, respectively. Differential expression genes (DEGs) in BRCA samples compared with their paracancerous samples in the training set were identified by using the edgeR Bioconductor package. Univariate Cox regression analysis and LASSO Cox regression method were applied to screen optimal genes for constructing a radiotherapy sensitivity estimation signature. Nomogram combining independent prognostic factors was used to predict 1-, 3-, and 5-year OS of radiation-treated BRCA patients. Relative proportions of tumor infiltrating immune cells (TIICs) calculated by CIBERSORT and mRNA levels of key immune checkpoint receptors was adopted to explore the relation between the signature and tumor immune response. As a result, 603 DEGs were obtained in BRCA tumor samples, six of which were retained and used to construct the radiotherapy sensitivity prediction model. The signature was proved to be robust in both training and testing sets. In addition, the signature was closely related to the immune microenvironment of BRCA in the context of TIICs and immune checkpoint receptors’ mRNA levels. In conclusion, the present study obtained a radiotherapy sensitivity estimation signature for BRCA, which should shed new light in clinical and experimental research.

scholarly journals Prognostic Value of an Autophagy-Related Five-Gene Signature for Lower-Grade Glioma Patients

2021 ◽  
Vol 11 ◽  
Author(s):  
Jin-Cheng Guo ◽  
Qing-Shuang Wei ◽  
Lei Dong ◽  
Shuang-Sang Fang ◽  
Feng Li ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Cox Regression ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
The Cancer Genome Atlas ◽  
Molecular Characteristics ◽  
Lower Grade ◽  
Cox Regression Analysis ◽  
Tcga Dataset ◽  
Genome Atlas

Background: Molecular characteristics can be good indicators of tumor prognosis and have been introduced into the classification of gliomas. The prognosis of patients with newly classified lower-grade gliomas (LGGs, including grade 2 and grade 3 gliomas) is highly heterogeneous, and new molecular markers are urgently needed.Methods: Autophagy related genes (ATGs) were obtained from Human Autophagy Database (HADb). From the Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA), gene expression profiles including ATG expression information and patient clinical data were downloaded. Cox regression analysis, receiver operating characteristic (ROC) analysis, Kaplan–Meier analysis, random survival forest algorithm (RSFVH) and stratification analysis were performed.Results: Through univariate Cox regression analysis, we found a total of 127 ATGs associated with the prognosis of LGG patients from TCGA dataset and a total of 131 survival-related ATGs from CGGA dataset. Using TCGA dataset as the training group (n = 524), we constructed a five-ATG signature (including BAG1, BID, MAP1LC3C, NRG3, PTK6), which could divide LGG patients into two risk groups with significantly different overall survival (Log Rank P < 0.001). Then we confirmed in the independent CGGA dataset that the five-ATG signature had the ability to predict prognosis (n = 431, Log Rank P < 0.001). We further discovered that the predictive ability of the five-ATG signature was better than the existing clinical indicators and IDH mutation status. In addition, the five-ATG signature could further classify patients after receiving radiotherapy or chemotherapy into groups with different prognosis.Conclusions: We identified a five-ATG signature that could be a reliable prognostic marker and might be therapeutic targets for autophagy therapy for LGG patients.

scholarly journals Identification of a prognostic long non-coding RNA signature in breast cancer

2020 ◽  
Author(s):  
Gaochen Lan ◽  
Xiaoling Yu ◽  
Yanna Zhao ◽  
Jinjian Lan ◽  
Wan Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cox Regression ◽  
Prognostic Biomarker ◽  
Expression Profiles ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Cox Regression Analysis

Abstract Background: Breast cancer is the most common malignant disease among women. At present, more and more attention has been paid to long non-coding RNAs (lncRNAs) in the field of breast cancer research. We aimed to investigate the expression profiles of lncRNAs and construct a prognostic lncRNA for predicting the overall survival (OS) of breast cancer.Methods: The expression profiles of lncRNAs and clinical data with breast cancer were obtained from The Cancer Genome Atlas (TCGA). Differentially expressed lncRNAs were screened out by R package (limma). The survival probability was estimated by the Kaplan‑Meier Test. The Cox Regression Model was performed for univariate and multivariate analysis. The risk score (RS) was established on the basis of the lncRNAs’ expression level (exp) multiplied regression coefficient (β) from the multivariate cox regression analysis with the following formula: RS=exp a1 * β a1 + exp a2 * β a2 +……+ exp an * β an. Functional enrichment analysis was performed by Metascape.Results: A total of 3404 differentially expressed lncRNAs were identified. Among them, CYTOR, MIR4458HG and MAPT-AS1 were significantly associated with the survival of breast cancer. Finally, The RS could predict OS of breast cancer (RS=exp CYTOR * β CYTOR + exp MIR4458HG * β MIR4458HG + exp MAPT-AS1 * β MAPT-AS1). Moreover, it was confirmed that the three-lncRNA signature could be an independent prognostic biomarker for breast cancer (HR=3.040, P=0.000).Conclusions: This study established a three-lncRNA signature, which might be a novel prognostic biomarker for breast cancer.

scholarly journals Identification of Hub Prognosis-Associated Oxidative Stress Genes in Pancreatic Cancer Using Integrated Bioinformatics Analysis

2020 ◽  
Vol 11 ◽  
Author(s):  
Xin Qiu ◽  
Qin-Han Hou ◽  
Qiu-Yue Shi ◽  
Hai-Xing Jiang ◽  
Shan-Yu Qin
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Pancreatic Cancer ◽  
Cancer Progression ◽  
Risk Model ◽  
Cox Regression ◽  
Expression Profiles ◽  
The Cancer Genome Atlas ◽  
Differentially Expressed ◽  
Cox Regression Analysis

BackgroundIntratumoral oxidative stress (OS) has been associated with the progression of various tumors. However, OS has not been considered a candidate therapeutic target for pancreatic cancer (PC) owing to the lack of validated biomarkers.MethodsWe compared gene expression profiles of PC samples and the transcriptome data of normal pancreas tissues from The Cancer Genome Atlas (TCGA) and Genome Tissue Expression (GTEx) databases to identify differentially expressed OS genes in PC. PC patients’ gene profile from the Gene Expression Omnibus (GEO) database was used as a validation cohort.ResultsA total of 148 differentially expressed OS-related genes in PC were used to construct a protein-protein interaction network. Univariate Cox regression analysis, least absolute shrinkage, selection operator analysis revealed seven hub prognosis-associated OS genes that served to construct a prognostic risk model. Based on integrated bioinformatics analyses, our prognostic model, whose diagnostic accuracy was validated in both cohorts, reliably predicted the overall survival of patients with PC and cancer progression. Further analysis revealed significant associations between seven hub gene expression levels and patient outcomes, which were validated at the protein level using the Human Protein Atlas database. A nomogram based on the expression of these seven hub genes exhibited prognostic value in PC.ConclusionOur study provides novel insights into PC pathogenesis and provides new genetic markers for prognosis prediction and clinical treatment personalization for PC patients.

scholarly journals Breast Cancer Case Identification Based on Deep Learning and Bioinformatics Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Dongfang Jia ◽  
Cheng Chen ◽  
Chen Chen ◽  
Fangfang Chen ◽  
Ningrui Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neural Network ◽  
Gene Expression ◽  
Expression Profiles ◽  
Differential Expression Analysis ◽  
Gene Expression Profiles ◽  
Diagnostic Methods ◽  
The Cancer Genome Atlas ◽  
Support Vector ◽  
Hub Genes

Mastering the molecular mechanism of breast cancer (BC) can provide an in-depth understanding of BC pathology. This study explored existing technologies for diagnosing BC, such as mammography, ultrasound, magnetic resonance imaging (MRI), computed tomography (CT), and positron emission tomography (PET) and summarized the disadvantages of the existing cancer diagnosis. The purpose of this article is to use gene expression profiles of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) to classify BC samples and normal samples. The method proposed in this article triumphs over some of the shortcomings of traditional diagnostic methods and can conduct BC diagnosis more rapidly with high sensitivity and have no radiation. This study first selected the genes most relevant to cancer through weighted gene co-expression network analysis (WGCNA) and differential expression analysis (DEA). Then it used the protein–protein interaction (PPI) network to screen 23 hub genes. Finally, it used the support vector machine (SVM), decision tree (DT), Bayesian network (BN), artificial neural network (ANN), convolutional neural network CNN-LeNet and CNN-AlexNet to process the expression levels of 23 hub genes. For gene expression profiles, the ANN model has the best performance in the classification of cancer samples. The ten-time average accuracy is 97.36% (±0.34%), the F1 value is 0.8535 (±0.0260), the sensitivity is 98.32% (±0.32%), the specificity is 89.59% (±3.53%) and the AUC is 0.99. In summary, this method effectively classifies cancer samples and normal samples and provides reasonable new ideas for the early diagnosis of cancer in the future.

scholarly journals Metabolic genes show excellent prognostic ability for clear cell renal cell carcinoma

2020 ◽  
Author(s):  
Chengjian Ji ◽  
Yichun Wang ◽  
Liangyu Yao ◽  
Jiaochen Luan ◽  
Rong Cong ◽  
...  
Keyword(s):  
Gene Expression ◽  
Renal Cell Carcinoma ◽  
Regression Analysis ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Cox Regression ◽  
Expression Profiles ◽  
Cell Renal Cell Carcinoma ◽  
Cox Regression Analysis ◽  
Metabolic Genes

Abstract Background Renal cell carcinoma (RCC) is one of the major malignant tumors of the urinary system, with a high mortality rate and a poor prognosis. Clear cell renal cell carcinoma (ccRCC) is the most common subtype of RCC. Although the diagnosis and treatment methods have been significantly improved, the incidence and mortality of ccRCC are high and still increasing. The occurrence and development of ccRCC are closely related to the changes of classic metabolic pathways. This article aims to explore the relationship between metabolic genes and the prognosis of patients with ccRCC. Patients and methods: Gene expression profiles of 63 normal kidney tissues and 446 ccRCC tissues from TCGA database and gene expression profiles of 39 ccRCC tissues from GEO database were used to obtain differentially expressed genes (DEGs) in ccRCC. Through the the KEGG gene sets of GSEA database, we obtained metabolic genes (MGs). Univariate Cox regression analysis was used to identify prognostic MGs. Lasso regression analysis was used to eliminate false positives because of over-fitting. Multivariate Cox regression analysis was used to established a prognostic model. Gene expression data and related survival data of 101 ccRCC patients from ArrayExpress database were used for external validation. Survival analysis, ROC curve analysis, independent prognostic analysis and clinical correlation analysis were performed to evaluate this model. Results We found that there were 479 abnormally expressed MGs in ccRCC tissues. Through univariate Cox regression analysis, Lasso regression analysis and multivariate Cox regression analysis, we identified 4 prognostic MGs (P4HA3, ETNK2, PAFAH2 and ALAD) and established a prognostic model (riskScore). Whether in the training cohort, the testing cohort or the entire cohort, this model could accurately stratify patients with different survival outcomes. The prognostic value of riskScore and 4 MGs was also confirmed in the ArrayExpress database. Results of GSEA analysis show that DEGs in patients with better prognosis were enriched in metabolic pathways. Then, a new Nomogram with higher prognostic value was constructed to better predict the 1-year OS, 3-year OS and 5-year OS of ccRCC patients. In addition, we successfully established a ceRNA network to further explain the differences in the expression of these MGs between high-risk patients and low-risk patients Conclusion We have successfully established a risk model (riskScore) based on 4 MGs, which could accurately predict the prognosis of patients with ccRCC. Our research may shed new light on ccRCC patients' prognosis and treatment management.

scholarly journals Identification and validation of an immune-related prognostic signature for hepatocellular carcinoma

2020 ◽  
Author(s):  
Xinxin Xia ◽  
Hui Liu ◽  
Yuejun Li
Keyword(s):  
Hepatocellular Carcinoma ◽  
Regression Analysis ◽  
Cox Regression ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Immune Gene ◽  
Regression Analyses ◽  
Prognostic Signature ◽  
Biological Mechanisms ◽  
Cox Regression Analysis

Abstract Background: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality. The immune system plays vital roles in HCC initiation and progression. The present study aimed to construct an immune-gene related prognostic signature (IRPS) for predicting the prognosis of HCC patients. Methods: Gene expression data were retrieved from The Cancer Genome Atlas database. Univariate Cox regression analysis was carried out to identify differentially expressed genes that associated with overall survival. The IRPS was established via Lasso and multivariate Cox regression analysis. Both Cox regression analyses were conducted to determine the independent prognostic factors for HCC. Next, the association between the IRPS and clinical-related factors were evaluated. The prognostic values of the IRPS were further validated using the International Cancer Genome Consortium (ICGC) dataset. Gene set enrichment analyses (GSEA) were conducted to understand the biological mechanisms of the IRPS. Results: A total of 62 genes were identified to be candidate immune-related prognostic genes. Transcription factors-immunogenes network was generated to explore the interactions among these candidate genes. According to the results of Lasso and multivariate Cox regression analysis, we established an IRPS and confirmed its stability and reliability in ICGC dataset. The IRPS was significantly associated with advanced clinicopathological characteristics. Both Cox regression analyses revealed that the IRPS could be an independent risk factor influencing the prognosis of HCC patients. The relationships between the IRPS and infiltration immune cells demonstrated that the IRPS was associated with immune cell infiltration. GSEA identified significantly enriched pathways, which might assist in elucidating the biological mechanisms of the IRPS. Furthermore, a nomogram was constructed to estimate the survival probability of HCC patients.Conclusions: The IRPS was effective for predicting prognosis of HCC patients, which might serve as novel prognostic and therapeutic biomarkers for HCC.

Identification and Validation of a Novel 16-Gene Prognostic Signature for Patients with Breast Cancer

2021 ◽  
Author(s):  
Zhenhua Zhong ◽  
Wenqiang Jiang ◽  
Jing Zhang ◽  
Zhanwen Li ◽  
Fengfeng Fan
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cox Regression ◽  
Molecular Taxonomy ◽  
Rna Degradation ◽  
The Cancer Genome Atlas ◽  
Gene Score ◽  
Disease Heterogeneity ◽  
Cox Regression Analysis ◽  
Risk Of Death

Abstract Background: Despite increased early diagnosis and improved treatment in breast cancer (BRCA) patients, prognosis prediction is still a challenging task due to the disease heterogeneity. This study was to identify a novel gene signature that can accurately evaluate BRCA patient survival. Methods: The gene expression and clinical data of BRCA patients were collected from The Cancer Genome Atlas (TCGA) and the Molecular Taxonomy of BRCA International Consortium (METABRIC) databases. Genes associated with prognosis were determined by Kaplan–Meier survival analysis and multivariate Cox regression analysis. A prognostic 16-gene score was established with linear combination of 16 genes. The prognostic value of the signature was validated in the METABRIC dataset. Gene expression analysis was performed to investigate the diagnostic values of 16 genes. Results: The 16-gene score was associated with shortened overall survival in BRCA patients independently of clinicopathological characteristics. The signalling pathways of cell cycle, oocyte meiosis, RNA degradation, progesterone mediated oocyte maturation and DNA replication were the top five most enriched pathways in the high 16-gene score group. The 16-gene nomogram incorporating the survival‐related clinical factors showed improved prediction accuracies for 1-year, 3-year and 5‐year survival (area under curve [AUC] = 0.91, 0.79 and 0.77 respectively). MORN3, IGJ, DERL1 exhibited high accuracy in differentiating BRCA tissues from normal breast tissues (AUC > 0.80 for all cases). Conclusions: The 16-gene profile provides novel insights into the identification of BRCA with a high risk of death, which eventually guides treatment decision making.

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 < 0.001), and In multivariate Cox regression analysis, the risk score was an independent predictive factor of OS ( HR>1, P<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.

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