scholarly journals Identification and Validation of Autophagy-Related Gene Nomograms to Predict the Prognostic Value of Patients with Cervical Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Jinqun Jiang ◽  
HongYan Xu ◽  
YiHao Wang ◽  
Hai Lu

Autophagy is a process of engulfing one’s own cytoplasmic proteins or organelles and coating them into vesicles, fusing with lysosomes to form autophagic lysosomes, and degrading the contents it encapsulates. Increasing studies have shown that autophagy disorders are closely related to the occurrence of tumors. However, the prognostic role of autophagy genes in cervical cancer is still unclear. In this study, we constructed risk signatures of autophagy-related genes (ARGs) to predict the prognosis of cervical cancer. The expression profiles and clinical information of autophagy gene sets were downloaded from TCGA and GSE52903 queues as training and validation sets. The normal cervical tissue expression profile data from the UCSC XENA website (obtained from GTEx) were used as a supplement to the TCGA normal cervical tissue. Univariate COX regression analysis of 17 different autophagy genes was performed with the consensus approach. Tumor samples from TCGA were divided into six subtypes, and the clinical traits of the six subtypes had different distributions. Further absolute shrinkage and selection operator (LASSO) and multivariable COX regression yielded an autophagy genetic risk model consisting of eight genes. In the training set, the survival rate of the high-risk group was lower than that of the low-risk group ( p  < 0.0001). In the validation set, the AUC area of the receiver operating characteristic (ROC) curve was 0.772 for the training set and 0.889 for the verification set. We found that high and low risk scores were closely related to TNM stage ( p  < 0.05). The nomogram shows that the risk score combined with other indicators, such as G, T, M, and N, better predicts 1-, 3-, and 5-year survival rates. Decline curve analysis (DCA) shows that the risk model combined with other indicators produces better clinical efficacy. Immune cells with an enrichment score of 28 showed statistically significant differences related to high and low risk. GSEA enrichment analysis showed the main enrichment being in KRAS activation, genes defining epithelial and mesenchymal transition (EMT), raised in response to the low oxygen level (hypoxia) gene and NF-kB in response to TNF. These pathways are closely related to the occurrence of tumors. Our constructed autophagy risk signature may be a prognostic tool for cervical cancer.

Author(s):  
JinQun Jiang ◽  
HongYan Xu ◽  
PingShen Zhao ◽  
Hai Lu

Cervical cancer is a common malignancy in women and has a poor prognosis.More and more studies have shown that autophagy disorder is closely related to the occurrence of tumors. However, the prognostic role of autophagy gene in cervical cancer is still unclear. In this study, we constructed the risk signatures of autophagy related genes to predict the prognosis of cervical cancer. The expression profiles and clinical information of autophagy gene sets were downloaded from the TCGA and GES52903 queues as training sets and validation sets. The cervical normal tissue expression profile data from UCSC XENA website is GTEx data as a supplement to TCGA normal cervical tissue. Univariate COX regression analysis of 17 different autophagy genes with the Consensus approach tumor samples from the TCGA is divided into six subtypes, and the clinical traits in the six subtypes have different distribution, with further then absolute shrinkage and selection operator (LASSO) and multiariable COX regression method finally got seven autophagy genetic risk model is constructed, in the training set, the survival rate of high risk group is lower than the low risk group (p &lt; 0.0001), the validation set,The AUC area of the receiver operating characteristic (ROC) curve, the training set is 0.894, and the verification set is 0.736. We find that the high and low risk score is closely related to the TMN stage (All P is less than 0.05).The nomogram shows that the risk score combined with other indicators such as age, G,T,M, and N better predicts 1-year, 2-year, 3-year survival, and the DCA curve shows that the risk model combined with other indicators produces better clinical efficacy.Then immune cells in 28 in the enrichment score, there were statistically significant differences, high and low risk most GSEA enrichment analysis, the main enrichment in G2 / M checkpoint high-risk score, Genes defining epithelial and mesenchymal transition, raised in response to the low oxygen levels (hypoxia) gene, gene is important to the mitotic spindle assembly, these are closely related with the occurrence of tumor . In conclusion, our constructed autophagy risk signature may be a prognostic tool for cervical cancer.


2020 ◽  
Author(s):  
Jianfeng Zheng ◽  
Jinyi Tong ◽  
Benben Cao ◽  
Xia Zhang ◽  
Zheng Niu

Abstract Background: Cervical cancer (CC) is a common gynecological malignancy for which prognostic and therapeutic biomarkers are urgently needed. The signature based on immune‐related lncRNAs(IRLs) of CC has never been reported. This study aimed to establish an IRL signature for patients with CC.Methods: The RNA-seq dataset was obtained from the TCGA, GEO, and GTEx database. The immune scores(IS)based on single-sample gene set enrichment analysis (ssGSEA) were calculated to identify the IRLs, which were then analyzed using univariate Cox regression analysis to identify significant prognostic IRLs. A risk score model was established to divide patients into low-risk and high-risk groups based on the median risk score of these IRLs. This was then validated by splitting TCGA dataset(n=304) into a training-set(n=152) and a valid-set(n=152). The fraction of 22 immune cell subpopulations was evaluated in each sample to identify the differences between low-risk and high-risk groups. Additionally, a ceRNA network associated with the IRLs was constructed.Results: A cohort of 326 CC and 21 normal tissue samples with corresponding clinical information was included in this study. Twenty-eight IRLs were collected according to the Pearson’s correlation analysis between immune score and lncRNA expression (P < 0.01). Four IRLs (BZRAP1-AS1, EMX2OS, ZNF667-AS1, and CTC-429P9.1) with the most significant prognostic values (P < 0.05) were identified which demonstrated an ability to stratify patients into low-risk and high-risk groups by developing a risk score model. It was observed that patients in the low‐risk group showed longer overall survival (OS) than those in the high‐risk group in the training-set, valid-set, and total-set. The area under the curve (AUC) of the receiver operating characteristic curve (ROC curve) for the four IRLs signature in predicting the one-, two-, and three-year survival rates were larger than 0.65. In addition, the low-risk and high-risk groups displayed different immune statuses in GSEA. These IRLs were also significantly correlated with immune cell infiltration. Conclusions: Our results showed that the IRL signature had a prognostic value for CC. Meanwhile, the specific mechanisms of the four-IRLs in the development of CC were ascertained preliminarily.


Author(s):  
Shangrong Wu ◽  
Zhiguo Du ◽  
Sanying Shen ◽  
Bo Zhang ◽  
Hong Yang ◽  
...  

Abstract Background Our aim in this study was to identify a prognostic biomarker to predict the disease prognosis and reduce the mortality rate of coronavirus disease 2019 (COVID-19), which has caused a worldwide pandemic. Methods COVID-19 patients were randomly divided into training and test groups. Univariate and multivariate Cox regression analyses were performed to identify the disease prognosis signature, which was selected to establish a risk model in the training group. The disease prognosis signature of COVID-19 was validated in the test group. Results The signature of COVID-19 was combined with the following 5 indicators: neutrophil count, lymphocyte count, procalcitonin, age, and C-reactive protein. The signature stratified patients into high- and low-risk groups with significantly relevant disease prognosis (log-rank test, P &lt; .001) in the training group. The survival analysis indicated that the high-risk group displayed substantially lower survival probability than the low-risk group (log-rank test, P &lt; .001). The area under the receiver operating characteristic (ROC) curve showed that the signature of COVID-19 displayed the highest predictive accuracy regarding disease prognosis, which was 0.955 in the training group and 0.945 in the test group. The ROC analysis of both groups demonstrated that the predictive ability of the signature surpassed the use of each of the 5 indicators alone. Conclusions The signature of COVID-19 presents a novel predictor and prognostic biomarker for closely monitoring patients and providing timely treatment for those who are severely or critically ill.


2020 ◽  
Vol 11 ◽  
Author(s):  
Peijie Chen ◽  
Yuting Gao ◽  
Si Ouyang ◽  
Li Wei ◽  
Min Zhou ◽  
...  

Objectives: The study is performed to analyze the relationship between immune-related long non-coding RNAs (lncRNAs) and the prognosis of cervical cancer patients. We constructed a prognostic model and explored the immune characteristics of different risk groups.Methods: We downloaded the gene expression profiles and clinical data of 227 patients from The Cancer Genome Atlas database and extracted immune-related lncRNAs. Cox regression analysis was used to pick out the predictive lncRNAs. The risk score of each patient was calculated based on the expression level of lncRNAs and regression coefficient (β), and a prognostic model was constructed. The overall survival (OS) of different risk groups was analyzed and compared by the Kaplan–Meier method. To analyze the distribution of immune-related genes in each group, principal component analysis and Gene set enrichment analysis were carried out. Estimation of STromal and Immune cells in MAlignant Tumors using Expression data was performed to explore the immune microenvironment.Results: Patients were divided into training set and validation set. Five immune-related lncRNAs (H1FX-AS1, AL441992.1, USP30-AS1, AP001527.2, and AL031123.2) were selected for the construction of the prognostic model. Patients in the training set were divided into high-risk group with longer OS and low-risk group with shorter OS (p = 0.004); meanwhile, similar result were found in validation set (p = 0.013), combination set (p &lt; 0.001) and patients with different tumor stages. This model was further confirmed in 56 cervical cancer tissues by Q-PCR. The distribution of immune-related genes was significantly different in each group. In addition, the immune score and the programmed death-ligand 1 expression of the low-risk group was higher.Conclusions: The prognostic model based on immune-related lncRNAs could predict the prognosis and immune status of cervical cancer patients which is conducive to clinical prognosis judgment and individual treatment.


2021 ◽  
Vol 104 (1) ◽  
pp. 003685042110065
Author(s):  
Jing Wan ◽  
Peigen Chen ◽  
Yu Zhang ◽  
Jie Ding ◽  
Yuebo Yang ◽  
...  

Endometrial carcinoma (EC) is the fourth most common cancer in women. Some long non-coding RNAs (lncRNAs) are regarded as potential prognostic biomarkers or targets for treatment of many types of cancers. We aim to screen prognostic-related lncRNAs and build a possible lncRNA signature which can effectively predict the survival of patients with EC. We obtained lncRNA expression profiling from the TCGA database. The patients were classified into training set and verification set. By performing Univariate Cox regression model, Robust likelihood-based survival analysis, and Cox proportional hazards model, we developed a risk score with the Cox co-efficient of individual lncRNAs in the training set. The optimum cut-off point was selected by ROC analysis. Patients were effectively divided into high-risk group and low-risk group according to the risk score. The OS of the low-risk patients was significantly prolonged compared with that of the high-risk group. At last, we validated this 11-lncRNA signature in the verification set and the complete set. We identified an 11-lncRNA expression signature with high stability and feasibility, which can predict the survival of patients with EC. These findings provide new potential biomarkers to improve the accuracy of prognosis prediction of EC.


2021 ◽  
Vol 8 ◽  
Author(s):  
Shenglan Huang ◽  
Jian Zhang ◽  
Xiaolan Lai ◽  
Lingling Zhuang ◽  
Jianbing Wu

Introduction: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors with poor prognosis. The tumor microenvironment (TME) plays a vital role in HCC progression. Thus, this research was designed to analyze the correlation between the TME and the prognosis of HCC patients and to construct a TME-related long noncoding RNA (lncRNA) signature to determine HCC patients’ prognosis and response to immunotherapy.Methods: We assessed the stromal–immune–estimate scores within the HCC microenvironment using the ESTIMATE (Estimation of Stromal and Immune Cells in Malignant Tumor Tissues Using Expression Data) algorithm based on The Cancer Genome Atlas database, and their associations with survival and clinicopathological parameters were also analyzed. Thereafter, differentially expressed lncRNAs were filtered out according to the immune and stromal scores. Cox regression analysis was performed to build a TME-related lncRNA risk signature. Kaplan–Meier analysis was used to explore the prognostic value of the risk signature. Furthermore, we explored the biological functions and immune microenvironment features in the high- and low-risk groups. Lastly, we probed the association of the risk model with treatment responses to immune checkpoint inhibitors (ICIs) in HCC.Results: The stromal, immune, and estimate scores were obtained utilizing the ESTIMATE algorithm for patients with HCC. Kaplan–Meier analysis showed that high scores were significantly correlated with better prognosis in HCC patients. Six TME-related lncRNAs were screened to construct the prognostic model. The Kaplan–Meier curves suggested that HCC patients with low risk had better prognosis than those with high risk. Receiver operating characteristic (ROC) curve and Cox regression analyses indicated that the risk model could predict HCC survival exactly and independently. Functional enrichment analysis revealed that some tumor- and immune-related pathways were activated in the high-risk group. We also revealed that some immune cells, which were important in enhancing immune responses toward cancer, were significantly increased in the low-risk group. In addition, there was a close correlation between ICIs and the risk signature, which can be used to predict the treatment responses of HCC patients.Conclusion: We analyzed the influence of the stromal, immune, and estimate scores on the prognosis of HCC patients. A novel TME-related lncRNA risk model was established, which could be effectively applied as an independent prognostic biomarker and predictor of ICIs for HCC patients.


2021 ◽  
Vol 11 ◽  
Author(s):  
Feng Xu ◽  
Huan Xu ◽  
Zixiong Li ◽  
Yuanyuan Huang ◽  
Xiaoling Huang ◽  
...  

While increased glycolysis has been identified as a cancer marker and attracted much attention in thyroid cancer (THCA), the prognostic role of it remains to be further elucidated. Here we aimed to determine a specific glycolysis-associated risk model to predict THCA patients' survival. We also explored the interaction between this signature and tumor immune microenvironment and performed drug screening to identify specific drugs targeting the glycolysis-associated signature. Six genes (CHST6, POM121C, PPFIA4, STC1, TGFBI, and FBP2) comprised the specific model, which was an independent prognostic indicator in THCA patients determined by univariate, LASSO and multivariate Cox regression analyses. The receiver operating characteristic (ROC) curve analysis confirmed the excellent clinical performance of the prognostic signature. According to the specific gene signature, patients were categorized into high- and low-risk subgroups. The high-risk group was characterized by decreased immune score and elevated tumor purity, as well as worser survival prognosis compared to the low-risk group. We also validated the expression of these genes in clinical samples and in-vitro experiments. Lastly, we identified potential drugs targeting the glycolysis-associated signature. The derived glycolysis-related signature is an independent prognostic biomarker for THCA patients and might be used as an efficacy of biomarker for drug-sensitivity prediction.


2021 ◽  
Author(s):  
Fang Wen ◽  
Xiaoxue Chen ◽  
Wenjie Huang ◽  
Shuai Ruan ◽  
Suping Gu ◽  
...  

Abstract Background: The diagnosis rate and mortality of gastric cancer (GC) are among the highest in the global, so it is of great significance to predict the survival time of GC patients. Ferroptosis and iron-metabolism make a critical impact on tumor development and are closely linked to the treatment of cancer and the prognosis of patients. However, the predictive value of the genes involved in ferroptosis and iron-metabolism in GC and their effects on immune microenvironment remain to be further clarified.Methods: In this study, the RNA sequence information and general clinical indicators of GC patients were acquired from the public databases. We first systematically screen out 134 DEGs and 13 PRGs related to ferroptosis and iron-metabolism. Then, we identified six PRDEGs (GLS2, MTF1, SLC1A5, SP1, NOX4, and ZFP36) based on the LASSO-penalized Cox regression analysis. The 6-gene prognostic risk model was established in the TCGA cohort and the GC patients were separated into the high- and the low-risk groups through the risk score median value. GEO cohort was used for verification. The expression of PRDEGs was verified by quantitative QPCR.Results: Our study demonstrated that patients in the low-risk group had a higher survival probability compared with those in high-risk group. In addition, univariate and multivariate Cox regression analyses confirmed that the risk score was an independent prediction parameter. The ROC curve analysis and nomogram manifested that the risk model had the high predictive ability and was more sensitive than general clinical features. Furthermore, compared with the high-risk group, the low-risk group had higher TMB and a longer 5-year survival period. In the immune microenvironment of GC, there were also differences in immune function and highly infiltrated immune cells between the two risk groups.Conclusions: The prognostic risk model based on the six genes associated with ferroptosis and iron-metabolism has a good performance for predicting the prognosis of patients with GC. The treatment of cancer by inducing tumor ferroptosis or mediating tumor iron-metabolism, especially combined with immunotherapy, provides a new possibility for individualized treatment of GC patients.


2021 ◽  
Author(s):  
Ziyan Chen ◽  
Haitao Yu ◽  
Lijun Wu ◽  
Sina Zhang ◽  
Zhihui Lin ◽  
...  

Introduction: Selecting the hub genes associated with hepatocellular carcinoma (HCC) to construct a COX regression model for predicting prognosis in HCC patients. Methods: Using HCC patient data from the ICGC and TCGA databases, screened for 40 core genes highly correlated with histological grade of HCC. Univariate and multivariate COX regression analysis were performed on the genes highly associated with HCC prognosis and the model was established. The expression of those genes was measured by immunohistochemistry in 110 HCC patients who underwent the surgery in The First Affiliated Hospital of Wenzhou Medical University. The survival of HCC patients was analyzed by the Kaplan-Meier method. Results: Eight genes (CDC45, CENPA, MCM10, MELK, CDC20, ASF1B, FANCD2 and NCAPH) were correlated with prognosis, and the same result was observed in 110 HCC patients. Using the regression model, the HCC patients in the training set were classified as high- and low-risk groups. The overall survival (OS) of patients in the high-risk group was shorter than that in the low-risk group, the same results were obtained in verification set. Conclusion: This study found that the risk model according to these eight genes can be used as a predictor of prognosis in HCC. These genes may become alternative biomarkers and therapeutic targets and provide new therapeutic strategies for HCC.


Author(s):  
Yue Li ◽  
Ruoyi Shen ◽  
Anqi Wang ◽  
Jian Zhao ◽  
Jieqi Zhou ◽  
...  

BackgroundLung adenocarcinoma (LUAD) originates mainly from the mucous epithelium and glandular epithelium of the bronchi. It is the most common pathologic subtype of non-small cell lung cancer (NSCLC). At present, there is still a lack of clear criteria to predict the efficacy of immunotherapy. The 5-year survival rate for LUAD patients remains low.MethodsAll data were downloaded from The Cancer Genome Atlas (TCGA) database. We used Gene Set Enrichment Analysis (GSEA) database to obtain immune-related mRNAs. Immune-related lncRNAs were acquired by using the correlation test of the immune-related genes with R version 3.6.3 (Pearson correlation coefficient cor = 0.5, P &lt; 0.05). The TCGA-LUAD dataset was divided into the testing set and the training set randomly. Based on the training set to perform univariate and multivariate Cox regression analyses, we screened prognostic immune-related lncRNAs and given a risk score to each sample. Samples were divided into the high-risk group and the low-risk group according to the median risk score. By the combination of Kaplan–Meier (KM) survival curve, the receiver operating characteristic (ROC) (AUC) curve, the independent risk factor analysis, and the clinical data of the samples, we assessed the accuracy of the risk model. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed on the differentially expressed mRNAs between the high-risk group and the low-risk group. The differentially expressed genes related to immune response between two risk groups were analyzed to evaluate the role of the model in predicting the efficacy and effects of immunotherapy. In order to explain the internal mechanism of the risk model in predicting the efficacy of immunotherapy, we analyzed the differentially expressed genes related to epithelial-mesenchymal transition (EMT) between two risk groups. We extracted RNA from normal bronchial epithelial cell and LUAD cells and verified the expression level of lncRNAs in the risk model by a quantitative real-time polymerase chain reaction (qRT-PCR) test. We compared our risk model with other published prognostic signatures with data from an independent cohort. We transfected LUAD cell with siRNA-LINC0253. Western blot analysis was performed to observed change of EMT-related marker in protein level.ResultsThrough univariate Cox regression analysis, 24 immune-related lncRNAs were found to be strongly associated with the survival of the TCGA-LUAD dataset. Utilizing multivariate Cox regression analysis, 10 lncRNAs were selected to establish the risk model. The K-M survival curves and the ROC (AUC) curves proved that the risk model has a fine predictive effect. The GO enrichment analysis indicated that the effect of the differentially expressed genes between high-risk and low-risk groups is mainly involved in immune response and intercellular interaction. The KEGG enrichment analysis indicated that the differentially expressed genes between high-risk and low-risk groups are mainly involved in endocytosis and the MAPK signaling pathway. The expression of genes related to the efficacy of immunotherapy was significantly different between the two groups. A qRT-PCR test verified the expression level of lncRNAs in LUAD cells in the risk model. The AUC of ROC of 5 years in the independent validation dataset showed that this model had superior accuracy. Western blot analysis verified the change of EMT-related marker in protein level.ConclusionThe immune lncRNA risk model established by us could better predict the prognosis of patients with LUAD.


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