A Transcription Factor Signature Predicts Prognosis of Patients with Adrenocortical Carcinoma

Abstract Background: Adrenocortical carcinoma (ACC) is a rare endocrine cancer that manifests as abdominal masses and excessive steroid hormone levels. Transcription factors (TFs) deregulation is found to be involved in adrenocortical tumorigenesis and cancer progression. This study aimed to construct a TF-based prognostic signature for prediction of survival of ACC patients.Methods: The gene expression profile for ACC patients were downloaded from TCGA and GEO datasets. The univariate Cox analysis was applied to identify survival-related TFs and the LASSO Cox regression was conducted to construct the TF signature. The multivariate analysis was used to reveal the independent prognostic factors.Results: We identified a 13-TF prognostic signature comprised of CREB3L3, NR0B1, CENPA, FOXM1, E2F2, MYBL2, HOXC11, ZIC2, ZNF282, DNMT1, TCF3, ELK4, and KLF6 using the univariate Cox analysis and LASSO Cox regression. The risk score based on the TF-signature could classify patients into low- and high-risk group. Kaplan-Meier analyses showed that patients in the high-risk group had significantly shorter overall survival compared to the low-risk patients. ROC curves showed that the prognostic signature predicted the overall survival of ACC patients with good sensitivity and specificity. Furthermore, the TF-risk score was an independent prognostic factor.Conclusion: Taken together, we identified a 13-TF prognostic marker to predict overall survival in ACC patients.

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A Transcription Factor Signature Predicts Prognosis of Patients with Adrenocortical Carcinoma

10.21203/rs.3.rs-151903/v1 ◽

2021 ◽

Author(s):

Jianyu Zhao ◽

Bo Liu ◽

Xiaoping Li

Keyword(s):

Overall Survival ◽

High Risk ◽

Cancer Progression ◽

Risk Score ◽

Adrenocortical Carcinoma ◽

Cox Regression ◽

Risk Group ◽

High Risk Group ◽

Prognostic Signature ◽

Abdominal Masses

Abstract Background: Adrenocortical carcinoma (ACC) is a rare endocrine cancer that manifests as abdominal masses and excessive steroid hormone levels. Transcription factors (TFs) deregulation is found to be involved in adrenocortical tumorigenesis and cancer progression. This study aimed to construct a TF-based prognostic signature for prediction of survival of ACC patients.Results: We identified a 13-TF prognostic signature comprised of CREB3L3, NR0B1, CENPA, FOXM1, E2F2, MYBL2, HOXC11, ZIC2, ZNF282, DNMT1, TCF3, ELK4, and KLF6 using the univariate Cox analysis and LASSO Cox regression. The risk score based on the TF-signature could classify patients into low- and high-risk group. Kaplan-Meier analyses showed that patients in the high-risk group had significantly shorter overall survival compared to the low-risk patients. ROC curves showed that the prognostic signature predicted the overall survival of ACC patients with good sensitivity and specificity. Furthermore, the TF-risk score was an independent prognostic factor.Conclusion: Taken together, we identified a 13-TF prognostic marker to predict overall survival in ACC patients.

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A transcription factor signature predicts prognosis of patients with adrenocortical carcinoma

10.21203/rs.3.rs-54684/v1 ◽

2020 ◽

Author(s):

Jianyu Zhao ◽

Bo Liu ◽

Xiaoping Li

Keyword(s):

Overall Survival ◽

High Risk ◽

Cancer Progression ◽

Risk Score ◽

Adrenocortical Carcinoma ◽

Cox Regression ◽

Risk Group ◽

High Risk Group ◽

Prognostic Signature ◽

Abdominal Masses

Abstract Background Adrenocortical carcinoma (ACC) is a rare endocrine cancer that manifests as abdominal masses and excessive steroid hormone levels. Transcription factors (TFs) deregulation is found to be involved in adrenocortical tumorigenesis and cancer progression. This study aimed to construct a TF-based prognostic signature for prediction of survival of ACC patients. Methods The gene expression profile for ACC patients were downloaded from TCGA and GEO datasets. The univariate Cox analysis was applied to identify survival-related TFs and the LASSO Cox regression was conducted to construct the TF signature. The multivariate analysis was used to reveal the independent prognostic factors. Results We identified a 13-TF prognostic signature comprised of CREB3L3, NR0B1, CENPA, FOXM1, E2F2, MYBL2, HOXC11, ZIC2, ZNF282, DNMT1, TCF3, ELK4, and KLF6. The risk score based on the TF-signature could classify patients into low- and high-risk group. Kaplan-Meier analyses showed that patients in the high-risk group had significantly shorter overall survival compared to the low-risk patients. ROC curves showed that the prognostic signature predicted the overall survival of ACC patients with good sensitivity and specificity. Furthermore, the TF-risk score was an independent prognostic factor. Conclusions Taken together, we identified a 13-TF prognostic marker to predict overall survival in ACC patients.

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A Hypoxia-related LncRNA Signature Predicts Survival of Primary Lower-grade glioma

10.21203/rs.3.rs-335140/v1 ◽

2021 ◽

Author(s):

Yanjia Hu ◽

Jing Zhang ◽

Jing Chen

Keyword(s):

High Risk ◽

Risk Score ◽

Cox Regression ◽

Risk Group ◽

Enrichment Analysis ◽

High Risk Group ◽

Gene Set Enrichment Analysis ◽

Lower Grade ◽

Prognostic Signature ◽

Gene Set Enrichment

Abstract Background Hypoxia-related long non-coding RNAs (lncRNAs) have been proven to play a role in multiple cancers and can serve as prognostic markers. Lower-grade gliomas (LGGs) are characterized by large heterogeneity. Methods This study aimed to construct a hypoxia-related lncRNA signature for predicting the prognosis of LGG patients. Transcriptome and clinical data of LGG patients were obtained from The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA). LGG cohort in TCGA was chosen as training set and LGG cohorts in CGGA served as validation sets. A prognostic signature consisting of fourteen hypoxia-related lncRNAs was constructed using univariate and LASSO Cox regression. A risk score formula involving the fourteen lncRNAs was developed to calculate the risk score and patients were classified into high- and low-risk groups based on cutoff. Kaplan-Meier survival analysis was used to compare the survival between two groups. Cox regression analysis was used to determine whether risk score was an independent prognostic factor. A nomogram was then constructed based on independent prognostic factors and assessed by C-index and calibration plot. Gene set enrichment analysis and immune cell infiltration analysis were performed to uncover further mechanisms of this lncRNA signature. Results LGG patients with high risk had poorer prognosis than those with low risk in both training and validation sets. Recipient operating characteristic curves showed good performance of the prognostic signature. Univariate and multivariate Cox regression confirmed that the established lncRNA signature was an independent prognostic factor. C-index and calibration plots showed good predictive performance of nomogram. Gene set enrichment analysis showed that genes in the high-risk group were enriched in apoptosis, cell adhesion, pathways in cancer, hypoxia etc. Immune cells were higher in high-risk group. Conclusion The present study showed the value of the 14-lncRNA signature in predicting survival of LGGs and these 14 lncRNAs could be further investigated to reveal more mechanisms involved in gliomas.

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Identification of a Pyroptosis-Related Gene Signature for Predicting Overall Survival and Response to Immunotherapy in Hepatocellular Carcinoma

Frontiers in Genetics ◽

10.3389/fgene.2021.789296 ◽

2021 ◽

Vol 12 ◽

Author(s):

Susu Zheng ◽

Xiaoying Xie ◽

Xinkun Guo ◽

Yanfang Wu ◽

Guobin Chen ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Overall Survival ◽

High Risk ◽

Regression Model ◽

Risk Score ◽

Cox Regression ◽

Risk Group ◽

Gene Signature ◽

High Risk Group ◽

Related Gene

Pyroptosis is a novel kind of cellular necrosis and shown to be involved in cancer progression. However, the diverse expression, prognosis and associations with immune status of pyroptosis-related genes in Hepatocellular carcinoma (HCC) have yet to be analyzed. Herein, the expression profiles and corresponding clinical characteristics of HCC samples were collected from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Then a pyroptosis-related gene signature was built by applying the least absolute shrinkage and selection operator (LASSO) Cox regression model from the TCGA cohort, while the GEO datasets were applied for verification. Twenty-four pyroptosis-related genes were found to be differentially expressed between HCC and normal samples. A five pyroptosis-related gene signature (GSDME, CASP8, SCAF11, NOD2, CASP6) was constructed according to LASSO Cox regression model. Patients in the low-risk group had better survival rates than those in the high-risk group. The risk score was proved to be an independent prognostic factor for overall survival (OS). The risk score correlated with immune infiltrations and immunotherapy responses. GSEA indicated that endocytosis, ubiquitin mediated proteolysis and regulation of autophagy were enriched in the high-risk group, while drug metabolism cytochrome P450 and tryptophan metabolism were enriched in the low-risk group. In conclusion, our pyroptosis-related gene signature can be used for survival prediction and may also predict the response of immunotherapy.

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A Prognostic Model for Hepatocellular Carcinoma Patients Based on Signature Ferroptosis-related Genes

10.21203/rs.3.rs-614871/v1 ◽

2021 ◽

Author(s):

Sizhe Wan ◽

Yiming Lei ◽

Mingkai Li ◽

Bin Wu

Keyword(s):

Overall Survival ◽

T Cells ◽

High Risk ◽

Risk Score ◽

Cox Regression ◽

Risk Group ◽

High Risk Group ◽

Low Risk ◽

Tnm Stage ◽

Functional Enrichment

Abstract BackgroundWith the increasing number of HCC patients, it is necessary to accurately predicting the prognosis of these patients. Ferroptosis has been confirmed to be closely related to HCC progression. However, there is still a challenge in predicting the survival of HCC patients through ferroptosis-related genes.MethodThe RNA-seq data and corresponding clinical data of HCC from TCGA database were downloaded to establish a prognosis model, and data of ICGC and GSE14520 as the validation set. The risk score was constructed with 5 genes identified by univariate and LASSO Cox regression analysis. Then, risk score, TNM stage and cirrhosis were included to construct a nomogram, through univariate and multivariate Cox regression analysis.Results5 genes were identified from 70 ferroptosis-related DEGs to construct a gene signature to predict HCC patient survival from TCGA cohort. PCA and heatmap results show that there are obvious differences in patients with different score groups. Then, we included risk score, TNM stage and cirrhosis to construct a nomogram to further predict the overall survival of the patients. Survival analysis indicates that overall survival of the low- risk group is significantly higher than that of the high-risk group. Similarly, the data in the GSE14520 cohort also confirmed good performance for the nomogram. Furthermore, KEGG and GO functional enrichment analyses indicates the difference in overall survival between groups is closely related to immune-related pathways. Finally, through analyzing the immune status of all patients, we found that compared with patients in the low-risk group, “Macrophages M0”, “T cells CD8”, and “T cells regulatory” of the high-risk group were significantly higher.ConclusionThe nomogram based on ferroptosis-related genes has a good performance for the prognosis of HCC patients. The model may provide a reference for evaluation of HCC patients by targeting ferroptosis.

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Construction of a Prognostic Signature in Ewing’s Sarcoma: Based On Metabolism-Related Genes

10.21203/rs.3.rs-364563/v1 ◽

2021 ◽

Author(s):

Bo Wu ◽

Dong Zhu ◽

Bo Yu ◽

Yuanyuan Hou ◽

Hongyu Wang ◽

...

Keyword(s):

Overall Survival ◽

Ewing’S Sarcoma ◽

Cox Regression ◽

Ewing's Sarcoma ◽

Risk Group ◽

Expression Profiles ◽

High Risk Group ◽

Prognostic Signature ◽

Cox Regression Analysis ◽

Cox Analysis

Abstract Objective: By combining the expression profiles of metabolism-related genes (MRGS) with clinical information, the expression quantities of MRGS and the influence on development and prognosis were systematically analyzed, so as to provide a theoretical basis for the clinical study on the prognosis of Ewing's sarcoma.Methods: MRGs expression profiles of 64 patients with Ewing's sarcoma were obtained from the GEO dataset. Univariate Cox regression analysis was used to identify metabolization-related differentially expressed genes (DEGs) related with prognosis in Ewing's sarcoma patients. Then, multivariate Cox analysis was used to calculate novel prognostic markers based on metabolism-related DEGs. Finally, the new prognostic index was verified on the basis of the prognostic models.Results: Univariate Cox regression analysis identified 20 metabolization-related DEGs, 9 of which were significantly associated with Ewing's sarcoma patients' overall survival. Subsequently, we used nine metabolism-related DEGs to construct metabolism-related prognostic signature for patients with Ewing's sarcoma. Based on the 9 DEGs regression coefficient, we put forward the formula of each patient's risk score, and then divided the patients into high-risk group and low-risk group. The results indicated that the survival rate and survival time were higher in the low-risk group and lower in the high-risk group. Multivariate Cox analysis showed that risk score index was indeed an independent prognostic factor for Ewing's sarcoma. In addition, the area under the receiver operating characteristic (ROC) curve for overall survival was 0.985. And a nomogram model was established.Conclusion: The experimental results suggest that the 9 metabolism-related DEGs marker may be effective in predicting the prognosis of Ewing's sarcoma to some extent, helping to individualize treatment of patients at different risks.

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A transcription factor signature predicts the survival of patients with adrenocortical carcinoma

PeerJ ◽

10.7717/peerj.12433 ◽

2021 ◽

Vol 9 ◽

pp. e12433

Author(s):

Jianyu Zhao ◽

Bo Liu ◽

Xiaoping Li

Keyword(s):

Gene Expression ◽

High Risk ◽

Risk Score ◽

Adrenocortical Carcinoma ◽

Cox Regression ◽

Gene Set Enrichment Analysis ◽

Prognostic Signature ◽

Training Set ◽

Abdominal Masses ◽

Validation Set

Background Adrenocortical carcinoma (ACC) is a rare endocrine cancer that manifests as abdominal masses and excessive steroid hormone levels and is associated with poor clinical outcomes. Transcription factors (TFs) deregulation is found to be involved in adrenocortical tumorigenesis and cancer progression. This study aimed to construct a TF-based prognostic signature for the prediction of survival of ACC patients. Methods The gene expression profile and clinical information for ACC patients were downloaded from The Cancer Genome Atlas (TCGA, training set) and Gene Expression Omnibus (GEO, validation set) datasets after obtained 1,639 human TFs from a previously published study. The univariate Cox regression analysis was applied to identify the survival-related TFs and the LASSO Cox regression was conducted to construct the TF signature based on these survival-associated TFs candidates. Then, multivariate analysis was used to reveal the independent prognostic factors. Furthermore, Gene Set Enrichment Analysis (GSEA) was performed to analyze the significance of the TFs constituting the prognostic signature. Results LASSO Cox regression and multivariate Cox regression identified a 13-TF prognostic signature comprised of CREB3L3, NR0B1, CENPA, FOXM1, E2F2, MYBL2, HOXC11, ZIC2, ZNF282, DNMT1, TCF3, ELK4, and KLF6. The risk score based on the TF signature could classify patients into low- and high-risk groups. Kaplan-Meier analyses showed that patients in the high-risk group had significantly shorter overall survival (OS) compared to the low-risk patients. Receiver operating characteristic (ROC) curves showed that the prognostic signature predicted the OS of ACC patients with good sensitivity and specificity both in the training set (AUC > 0.9) and the validation set (AUC > 0.7). Furthermore, the TF-risk score was an independent prognostic factor. Conclusions Taken together, we identified a 13-TF prognostic marker to predict OS in ACC patients.

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A Risk Signature of Nine Autophagy-Related Genes Associated With Immune Microenvironment and Clinical Prognosis in Wilms Tumor

10.21203/rs.3.rs-892534/v1 ◽

2021 ◽

Author(s):

Shaopei Ye ◽

Wenbin Tang ◽

Ke Huang

Keyword(s):

Regression Analysis ◽

High Risk ◽

Risk Score ◽

Cox Regression ◽

Wilms Tumor ◽

Risk Group ◽

High Risk Group ◽

Differentially Expressed ◽

Clinical Prognosis ◽

Cox Regression Analysis

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.

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Prognostic model of head and neck squamous cell carcinoma based on 12 ferroptosis-related genes

10.21203/rs.3.rs-349666/v1 ◽

2021 ◽

Author(s):

Sijia Li ◽

Hongyang Zhang ◽

Wei Li

Keyword(s):

Regression Analysis ◽

Risk Score ◽

Cox Regression ◽

Risk Group ◽

High Risk Group ◽

Risk Scores ◽

Cox Regression Analysis ◽

Normal Tissues ◽

Model Based ◽

Cox Analysis

Abstract Background: The purpose of our study is establishing a model based on ferroptosis-related genes predicting the prognosis of patients with head and neck squamous cell carcinoma (HNSCC).Methods: In our study, transcriptome and clinical data of HNSCC patients were from The Cancer Genome Atlas, ferroptosis-related genes and pathways were from Ferroptosis Signatures Database. Differentially expressed genes (DEGs) were screened by comparing tumor and adjacent normal tissues. Functional enrichment analysis of DEGs, protein-protein interaction network and gene mutation examination were applied. Univariate Cox regression analysis and least absolute shrinkage and selection operator (LASSO) regression were used to identified DEGs. The model was constructed by multivariate Cox regression analysis and verified by Kaplan-Meier analysis. The relationship between risk scores and other clinical features was also analyzed. Univariate and multivariate Cox analysis was used to verified the independence of our model. The model was evaluated by receiver operating characteristic analysis and calculation of the area under the curve (AUC). A nomogram model based on risk score, age, gender and TNM stages was constructed.Results: We analyzed data including 500 tumor tissues and 44 adjacent normal tissues and 259 ferroptosis-related genes, then obtained 73 DEGs. Univariate Cox regression analysis screened out 16 genes related to overall survival, and LASSO analysis fingered out 12 of them with prognostic value. A risk score model based on these 12 genes was constructed by multivariate Cox regression analysis. According to the median risk score, patients were divided into high-risk group and low-risk group. The survival rate of high-risk group was significantly lower than that of low-risk group in Kaplan-Meier curve. Risk scores were related to T and grade. Univariate and multivariate Cox analysis showed our model was an independent prognostic factor. The AUC was 0.669. The nomogram showed high accuracy predicting the prognosis of HNSCC patients.Conclusion: Our model based on 12 ferroptosis-related genes performed excellently in predicting the prognosis of HNSCC patients. Ferroptosis-related genes may be promising biomarkers for HNSCC treatment and prognosis.

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

Journal of Ovarian Research ◽

10.1186/s13048-020-00712-w ◽

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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