scholarly journals Expression profiling analysis of autophagy-related genes in cervical cancer

Author(s):  
Zhiyuan Huang ◽  
He Wang ◽  
Min Liu ◽  
Xinrui Li ◽  
Lei Zhu ◽  
...  

Abstract Background: It has been demonstrated by studies globally that autophagy took part in the development of cervical cancer (CC). Few studies concentrated on the correlation between overall survival and CC patients. We retrieved significant autophagy-related genes (ARGs) correlated to the process of cervical cancer. They may be used as prognosis marker or treatment target for clinical application.Methods: Expressions level of genes in cervical cancer and normal tissue samples were obtained from GTEx and TCGA database. Autophagy-related genes (ARGs) were retrieved accroding to the gene list from HaDB. Differentially expressed autophagy related genes (DE-ARGs) related to cervical cancer were identified by Wilcoxon signed-rank test. ClusterProfiler package worked in R software was used to perform GO and KEGG enrichment analyses. Univariate propotional hazard cox regression and multivariate propotional hazard cox regressions were applied to identify DE-ARGs equipped with prognostic value and other clinical independent risk factors. ROC curve was drawn for comparing the survival predict feasibility of risk score with other risk factors in CC patients. Nomogram was drawn to exhibit the prediction model constructed accroding to multivariate cox regression. Correlations between Differentially expressed autophagy related genes (DE-ARGs) and other clinical features were investigated by t test or Cruskal wallis analysis. Correlation between Immune and autophagy in cervical cancer was investigated by ssGSEA and TIMER database. Results: Fifty-six differentially expressed ARGs (DE-ARGs) were retrieved from cervical cancer tissue and normal tissue samples. GO enrichment analysis showed that these ARGs involved in autophagy, ubiquitination of protein and apoptosis. Cox regression medel showed that there were six ARGs significantly associated with overall survival of cervical caner patients. VAMP7 (HR = 0.599, P= 0.033) and TP73 (HR = 0.671, P= 0.014) played protective roles in survival among these six genes. Stage (Stage IV vs Stage I HR = 3.985, P<0.001) and risk score (HR = 1.353, P< 0.001) were sorted as independent prognostic risk factors based on multivariate cox regression. ROC curve validated that risk score was preferable to predict survival of CC patients than other risk factors. Additionally, we found some of these six predictor ARGs were correlated significantly in statistic with tumor grade or stage, clinical T stage, clinical N stage, pathology or risk score (all P< 0.05). The immune cells and immune functions showed a lower activity in high risk group than low risk group which is distincted by median risk score. Conclusion: Our discovery showed that autophagy genes involved in the progress of cervical cancer. Many autophagy-related genes could probably serve as prognostic biomarkers and accelerate the discovery of treatment targets for CC patients.

2021 ◽  
Author(s):  
Zhiyuan Huang ◽  
Fang Li ◽  
Qinchuan Li

Abstract Background: It has been demonstrated by studies globally that RNA binding proteins (RBPs) took part in the development of cervical cancer (CC). Few studies concentrated on the correlation between RBPs and overall survival of CC patients. We retrieved significant DEGs (differently expressed genes, RNA binding proteins) correlated to the process of cervical cancer development. Methods: Expressions level of genes in cervical cancer and normal tissue samples were obtained from GTEx and TCGA database. Differently expressed RNA binding proteins (DEGs) were retrieved by Wilcoxon sum-rank test. ClusterProfiler package worked in R software was used to perform GO and KEGG enrichment analyses. Univariate propotional hazard cox regression and multivariate propotional hazard cox regressions were applied to identify DEGs equipped with prognostic value and other clinical independent risk factors. ROC curve was drawn for comparing the survival predict feasibility of risk score with other risk factors in CC patients. Nomogram was drawn to exhibit the prediction model and validated by C-index and calibration curve. Correlations between Differentially expressed RNA binding proteins (DEGs) and other clinical features were investigated by t test or Cruskal wallis analysis. Correlation between Immune and DEGs in cervical cancer was investigated by ssGSEA. Results: 347 differentially expressed RBPs (DEGs) were retrieved from cervical cancer tissue and normal tissue samples. GO enrichment analysis showed that these DEGs involved in RNA splicing, catabolic process and metabolism. Cox regression medel showed that there were ten DEGs significantly associated with overall survival of cervical caner patients. WDR43 (HR = 0.423, P=0.008), RBM38 (HR = 0.533, P<0.001), RNASEH2A (HR=0.474, P=0.002) and HENMT1 (HR=0.720, P=0.071) played protective roles in survival among these ten genes. Stage (Stage IV vs Stage I HR = 3.434, P<0.001) and risk score (HR = 1.214, P< 0.001) were sorted as independent prognostic risk factors based on multivariate cox regression. ROC curve validated that risk score was preferable to predict survival of CC patients than other risk factors. Additionally, we found some of these ten predictor DEGs were correlated significantly in statistic with tumor grade or stage, clinical T stage, clinical N stage, pathology or risk score (all P< 0.05). Part of immune cells and immune functions showed a lower activity in high risk group than low risk group which is distincted by median risk score. Conclusion: Our discovery showed that many RNA binding proteins involved in the progress of cervical cancer, which could probably serve as prognostic biomarkers and accelerate the discovery of treatment targets for CC patients.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Zhiyuan Huang ◽  
Fang Li ◽  
Qinchuan Li

Abstract Background It has been demonstrated by studies globally that RNA binding proteins (RBPs) took part in the development of cervical cancer (CC). Few studies concentrated on the correlation between RBPs and overall survival of CC patients. We retrieved significant DEGs (differently expressed genes, RNA binding proteins) correlated to the process of cervical cancer development. Methods Expressions level of genes in cervical cancer and normal tissue samples were obtained from GTEx and TCGA database. Differently expressed RNA binding proteins (DEGs) were retrieved by Wilcoxon sum-rank test. ClusterProfiler package worked in R software was used to perform GO and KEGG enrichment analyses. Univariate proportional hazard cox regression and multivariate proportional hazard cox regressions were applied to identify DEGs equipped with prognostic value and other clinical independent risk factors. ROC curve was drawn for comparing the survival predict feasibility of risk score with other risk factors in CC patients. Nomogram was drawn to exhibit the prediction model and validated by C-index and calibration curve. Correlations between differentially expressed RNA binding proteins (DEGs) and other clinical features were investigated by t test or Cruskal Wallis analysis. Correlation between Immune and DEGs in cervical cancer was investigated by ssGSEA. Results 347 differentially expressed RBPs (DEGs) were retrieved from cervical cancer tissue and normal tissue samples. GO enrichment analysis showed that these DEGs involved in RNA splicing, catabolic process and metabolism. Cox regression model showed that there were ten DEGs significantly associated with overall survival of cervical cancer patients. WDR43 (HR = 0.423, P = 0.008), RBM38 (HR = 0.533, P < 0.001), RNASEH2A (HR = 0.474, P = 0.002) and HENMT1 (HR = 0.720, P = 0.071) played protective roles in survival among these ten genes. Stage (Stage IV vs Stage I HR = 3.434, P < 0.001) and risk score (HR = 1.214, P < 0.001) were sorted as independent prognostic risk factors based on multivariate cox regression. ROC curve validated that risk score was preferable to predict survival of CC patients than other risk factors. Additionally, we found some of these ten predictor DEGs were correlated significantly in statistic with tumor grade or stage, clinical T stage, clinical N stage, pathology or risk score (all P < 0.05). Part of immune cells and immune functions showed a lower activity in high risk group than low risk group which is stratified by median risk score. Conclusion Our discovery showed that many RNA binding proteins involved in the progress of cervical cancer, which could probably serve as prognostic biomarkers and accelerate the discovery of treatment targets for CC patients.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xuelong Wang ◽  
Bin Zhou ◽  
Yuxin Xia ◽  
Jianxin Zuo ◽  
Yanchao Liu ◽  
...  

Abstract Background DNA methylation alteration is frequently observed in Lung adenocarcinoma (LUAD) and may play important roles in carcinogenesis, diagnosis, and prognosis. Thus, this study aimed to construct a reliable methylation-based nomogram, guiding prognostic classification screening and personalized medicine for LUAD patients. Method The DNA methylation data, gene expression data and corresponding clinical information of lung adenocarcinoma samples were extracted from The Cancer Genome Atlas (TCGA) database. Differentially methylated sites (DMSs) and differentially expressed genes (DEGs) were obtained and then calculated correlation by pearson correlation coefficient. Functional enrichment analysis and Protein-protein interaction network were used to explore the biological roles of aberrant methylation genes. A prognostic risk score model was constructed using univariate Cox and LASSO analysis and was assessed in an independent cohort. A methylation-based nomogram that included the risk score and the clinical risk factors was developed, which was evaluated by concordance index and calibration curves. Result We identified a total of 1362 DMSs corresponding to 471 DEGs with significant negative correlation, including 752 hypermethylation sites and 610 hypomethylation sites. Univariate cox regression analysis showed that 59 DMSs were significantly associated with overall survival. Using LASSO method, we constructed a three-DMSs signature that was independent predictive of prognosis in the training cohort. Patients in high-risk group had a significant shorter overall survival than patients in low-risk group classified by three-DMSs signature (log-rank p = 1.9E-04). Multivariate cox regression analysis proved that the three-DMSs signature was an independent prognostic factor for LUAD in TCGA-LUAD cohort (HR = 2.29, 95%CI: 1.47–3.57, P = 2.36E-04) and GSE56044 cohort (HR = 2.16, 95%CI: 1.19–3.91, P = 0.011). Furthermore, a nomogram, combining the risk score with clinical risk factors, was developed with C-indexes of 0.71 and 0.70 in TCGA-LUAD and GSE56044 respectively. Conclusions The present study established a robust three-DMSs signature for the prediction of overall survival and further developed a nomogram that could be a clinically available guide for personalized treatment of LUAD patients.


2020 ◽  
Author(s):  
Xuelong Wang ◽  
Bin Zhou ◽  
Yuxin Xia ◽  
Jianxin Zuo ◽  
Yanchao Liu ◽  
...  

Abstract Background DNA methylation alteration is frequently observed in Lung adenocarcinoma (LUAD) and may play important roles in carcinogenesis, diagnosis, and prognosis. Thus, this study aimed to construct a reliable methylation-based nomogram, guiding prognostic classification screening and personalized medicine for LUAD patients. Method: The DNA methylation data, gene expression data and corresponding clinical information of lung adenocarcinoma samples were extracted from The Cancer Genome Atlas (TCGA) database. Differentially methylated sites (DMSs) and differentially expressed genes (DEGs) were obtained and then calculated expression correlation by pearson correlation coefficient. Functional enrichment analysis and Protein-protein interaction network were used to explore the biological roles of aberrant methylation genes. A prognostic risk score model was constructed using univariate Cox and LASSO analysis and was assessed in an independent cohort. A methylation-based nomogram that included the risk score and the clinical risk factors was developed, which was evaluated by concordance index and calibration curves. Result We identified a total of 1362 DMSs corresponding to 471 DEGs with significant negative correlation, including 752 hypermethylation sites and 610 hypomethylation sites. Univariate cox regression analysis showed that 59 DMSs were significantly associated with overall survival. Using LASSO method, we constructed a three-DMSs signature that was independent predictive of prognosis in the training cohort. Patients in high-risk group had a significant shorter overall survival than patients in low-risk group classified by three-DMSs signature (log-rank p = 1.9E-04). Multivariate cox regression analysis proved that the three-DMSs signature was an independent prognostic factor for LUAD in TCGA-LUAD cohort (HR = 2.29, 95%CI: 1.47–3.57, P = 2.36E-04) and GSE56044 cohort (HR = 2.16, 95%CI: 1.19–3.91, P = 0.011). Furthermore, a nomogram, combining the risk score with clinical risk factors, was developed with C-indexes of 0.71 and 0.70 in TCGA-LUAD and GSE56044 respectively. Conclusions The present study established a robust three-DMSs signature for the prediction of overall survival and further developed a nomogram that could be a clinically available guide for personalized treatment of LUAD patients.


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

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


2021 ◽  
Author(s):  
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.


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1189-1189
Author(s):  
Anne M Dickinson ◽  
Kim F Pearce ◽  
Graham H Jackson ◽  
Matthew Collin ◽  
Jean Norden ◽  
...  

Abstract Abstract 1189 Poster Board I-211 Introduction In the last decade, several groups have demonstrated that non-HLA gene polymorphisms can impact on outcome after HSCT. So far, their role appears as a matter of debate; non HLA genotyping is not yet routinely used. In addition, the main clinical factors influencing outcome after HSCT have also been described. Most experience has been gained through analyses of patients undergoing HSCT for chronic myeloid leukemia (CML). Patient age, stage of the disease, time interval from diagnosis to transplant, histocompatibility and donor and patient gender combination were initially identified as key pre-transplant risk factors for CML in the European Group for Blood and Marrow Transplantation (EBMT) clinical risk score, recently confirmed as risk factors for all patients with haematological indications for HSCT. Patients and Methods In this study, we assessed the additional impact of polymorphisms within the tumour necrosis factor receptor II (TNFRSF1B), estrogen receptor (ESR1), vitamin D receptor (VDR), interleukin 6 (IL6), interleukin 1 receptor antagonist (ILRN), interferon gamma (IFNG) and interleukin 4 (IL4) genes on overall survival in a EUROBANK cohort of 915 ( median patient age 41 years, range 16 years to 67 years; 59 % male patients) HLA identical sibling (n=501; 55%) and matched unrelated donor (MUD) (n=414; 45%) transplants consisting of patients having either acute leukaemia (AL) (n=463; 51%), CML (N=187; 20%), plasma cell neoplasia (n=120; 13%) or lymphoma (n=145; 16%) from 8 transplant centres (Barcelona, Paris, Munich, Newcastle-upon-Tyne, Prague, Regensburg, Vienna and Rostock). The statistical analysis was performed for the full cohort and for the AL subgroup. Potential influential genetic factors were assessed using the log rank test (p value < 0.2). These candidate factors were further included in addition to the EBMT clinical risk score in a stepwise Cox regression procedure to select final genes. The power of a model to predict overall survival was assessed through prediction error curves. Results For the full cohort, the SNP IL6−174 within the IL6 gene in donors improved the prediction of the outcome by EBMT clinical risk score. Specifically, the presence of allele C in the donor IL-6 genotype was associated with lower survival time. This SNP assessment only held true for the (combined) CML, lymphoma and plasma cell neoplasia subgroups (log rank, p=0.016), not for AL (log rank, p= 0.638). The AL subgroup, the largest, was further assessed separately. Absence of patient IL4 (any T) and presence of patient IL1RN (any C) were associated with lower survival time as shown by Kaplan Meier survival plots. When viewed together with the EBMT score, these two genotypes improved the predictive value. Patients with absence of patient IL4 (any T) and presence of patient IL1RN (any C) were assigned to the ‘high risk’ group; remaining patients were assigned to the low risk group - Figure 1A and B illustrate the lower probability of survival and higher incidence of transplant related mortality (TRM) in the high risk polymorphism AL group compared with the low risk group. Conclusions This study confirms the important role of non-HLA genotyping for risk assessment in allogeneic HSCT. Improvement of fit of the EBMT risk score presents a powerful novel tool to assess this impact of cytokine gene polymorphisms in a complex heterogeneous patient population such as HSCT. Disclosures No relevant conflicts of interest to declare.


2021 ◽  
Author(s):  
Shenglan Huang ◽  
Dan Li ◽  
Lingling Zhuang ◽  
Liying Sun ◽  
Jianbing Wu

Abstract Background:Gastric cancer (GC) is one of the most common malignant tumors with a poor prognosis. Ferroptosis is a novel and distinct type of non-apoptotic cell death that is closely associated with metabolism, redox biology, and tumor prognosis. Recently, ferroptosis-related long non-coding RNAs (lncRNAs) have received increasing attention in predicting cancer prognosis. Thus, we aimed to construct an ferroptosis-related lncRNAs signature for predicting the prognosis of patients with gastric cancer.Methods:We built an ferroptosis-related lncRNA risk signature by using Cox regression based on TCGA database. Kaplan-Meier survival analysis was conducted to compare the overall survival (OS) in different risk groups. Cox regression was performed to explore whether the signature could be used as an independent factor. A nomogram was built involving the risk score and clinicopathological features. Furthermore, we explored the biological functions and immune states in two groups.Results:Eight ferroptosis-related lncRNAs were obtained for constructing the prognosis model in gastric cancer. Kaplan–Meier curve analysis revealed that patients in the high-risk group had worse survival than those in the low-risk group. The survival outcome was also appropriate for subgroup analysis, including age, sex, grade, and clinical stage. Multivariate Cox regression analysis and receiver operating characteristic (ROC) curve analysis demonstrated that the risk score was an independent prognostic factor and superior to traditional clinicopathological features in predicting GC prognosis. Next, we established a nomogram according to clinical parameters (age, sex, grade, and clinical stage) and risk score. All the verified results, including ROC curve analysis, calibration curve, and decision curve analysis, demonstrated that the nomogram could accurately predict the survival of patients with gastric cancer. Gene set enrichment analysis revealed that these lncRNAs were mainly involved in cell adhesion, cancer pathways, and immune function regulation.Conclusion: We established a novel ferroptosis-related prognostic risk signature including eight lncRNAs and constructed a nomogram to predict the prognosis of gastric cancer patients, which may improve prognostic predictive accuracy and guide individualized treatment for patients with GC.


2021 ◽  
Vol 12 ◽  
Author(s):  
Susu Zheng ◽  
Xiaoying Xie ◽  
Xinkun Guo ◽  
Yanfang Wu ◽  
Guobin Chen ◽  
...  

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.


2021 ◽  
Author(s):  
Jianyu Zhao ◽  
Bo Liu ◽  
Xiaoping Li

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.


Sign in / Sign up

Export Citation Format

Share Document