scholarly journals Construction and Validation of a Universal Applicable Prognostic Signature for Gastric Cancer Based on Seven Immune-Related Gene Correlated With Tumor Associated Macrophages

2021 ◽  
Vol 11 ◽  
Author(s):  
Junyu Huo ◽  
Liqun Wu ◽  
Yunjin Zang
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Risk Score ◽  
Critical Role ◽  
External Validation ◽  
Low Risk ◽  
Prognostic Signature ◽  
Tumor Associated Macrophages ◽  
Cox Regression Analysis ◽  
Significant Difference

BackgroundTumor-associated macrophages (TAMs) play a critical role in the progression of malignant tumors, but the detailed mechanism of TAMs in gastric cancer (GC) is still not fully explored.MethodsWe identified differentially expressed immune-related genes (DEIRGs) between GC samples with high and low macrophage infiltration in The Cancer Genome Atlas datasets. A risk score was constructed based on univariate Cox analysis and Lasso penalized Cox regression analysis in the TCGA cohort (n=341). The optimal cutoff determined by the 5-year time-dependent receiver operating characteristic (ROC) curve was considered to classify patients into groups with high and low risk. We conducted external validation of the prognostic signature in four independent cohorts (GSE84437, n=431; GSE62254, n=300; GSE15459, n=191; and GSE26901, n=109) from the Gene Expression Omnibus (GEO) database.ResultsThe signature consisting of 7 genes (FGF1, GRP, AVPR1A, APOD, PDGFRL, CXCR4, and CSF1R) showed good performance in predicting overall survival (OS) in the 5 independent cohorts. The risk score presented an obviously positive correlation with macrophage abundance (cor=0.7, p<0.001). A significant difference was found between the high- and low-risk groups regarding the overall survival of GC patients. The high-risk group exhibited a higher infiltration level of M2 macrophages estimated by the CIBERSORT algorithm. In the five independent cohorts, the risk score was highly positively correlated with the stromal cell score, suggesting that we can also evaluate the infiltration of stromal cells in the tumor microenvironment according to the risk score.ConclusionOur study developed and validated a general applicable prognostic model for GC from the perspective of TAMs, which may help to improve the precise treatment strategy of GC.

scholarly journals Eleven immune-gene pairs signature associated with TP53 predicting the overall survival of gastric cancer: a retrospective analysis of large sample and multicenter from public database

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Junyu Huo ◽  
Liqun Wu ◽  
Yunjin Zang
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
T Cells ◽  
Risk Score ◽  
External Validation ◽  
Disease Free Survival ◽  
Low Risk ◽  
Immune Gene ◽  
Free Survival ◽  
Gene Pairs

Abstract Background Growing attention have been paid to the relationship between TP53 and tumor immunophenotype, but there are still lacking enough search on the field of gastric cancer (GC). Materials and methods We identified differential expressed immune-related genes (DEIRGs) between the TP53-altered GC samples (n = 183) and without TP53-altered GC samples (n = 192) in The Cancer Genome Atlas and paired them. In the TCGA cohort (n = 350), a risk score was determined through univariate and multivariate cox regression and Lasso regression analysis. Patients were divided into two groups, high-risk and low-risk, based on the median risk score. Four independent cohorts (GSE84437,n = 431; GSE62254, n = 300; GSE15459, n = 191; GSE26901, n = 100) from the Gene Expression Omnibus (GEO) database were used to validate the reliability and universal applicability of the model. Results The signature contained 11 gene pairs showed good performance in predicting progression-free survival (PFS), disease-free survival (DFS), disease special survival (DSS), and the overall survival (OS) for GC patients in the TCGA cohort. The subgroup analysis showed that the signature was suitable for GC patients with different characteristics. The signature could capable of distinguish GC patients with good prognosis and poor prognosis in all four independent external validation cohorts. The high- and low-risk groups differed significantly in the proportion of several immune cell infiltration, especially for the T cells memory resting, T cells memory activated and follicular helper, and Macrophage M0, which was also related to the prognosis of GC patients. Conclusion The present work proposed an innovative system for evaluating the prognosis of gastric cancer. Considering its stability and general applicability, which may become a widely used tool in clinical practice.

scholarly journals A signature of seven immune-related genes predicts overall survival in male gastric cancer patients

2020 ◽  
Author(s):  
Xin Xu ◽  
Youliang Wu ◽  
Mingliang Wang ◽  
Yida Lu ◽  
Xiaodong Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Overall Survival ◽  
Risk Score ◽  
Cox Regression ◽  
External Validation ◽  
Differentially Expressed ◽  
Survival Prediction ◽  
Cox Regression Analysis ◽  
Immune Related Genes

Abstract Background: Gastric cancer (GC) is one of the most fatal malignant tumors with a high mortality rate. Male sex has been proven as an independent risk factor for GC. This study aimed to identify immune-related genes (IRGs) for the prognosis of male GC.Method: RNA sequencing and clinical data were obtained from The Cancer Genome Atlas (TCGA) database. Differentially expressed IRGs between male GC and normal tissues were identified by integrated bioinformatics analysis. Univariate and multivariate Cox regression analysis were applied to screen survival-associated IRGs. Then, GC patients were separated into high- and low-risk groups based on the median risk score. Furthermore, a nomogram was constructed based on the TCGA dataset. The prognostic value of the risk signature model was evaluated by Kaplan-Meier curve, receiver operating characteristic (ROC), Harrell’s concordance index and calibration curves. In addition, the gene expression dataset from Gene Expression Omnibus (GEO) was also downloaded for external validation. The relative proportions of 22 types of infiltrating immune cells in each male GC sample were evaluated using CIBERSORT.Results: A total of 276 differentially expressed IRGs were screened, including 189 up-regulated and 87 down-regulated genes. Subsequently, a seven-IRGs signature (LCN12, CCL21, RNASE2, CGB5, NRG4, AGTR1 and NPR3) was identified and showed a significant association with the overall survival (OS) of male GC patients. Survival analysis indicated that patients with high-risk group exhibited a poor clinical outcome. The result of multivariate analysis revealed that the risk score was an independent prognostic factor. The established nomogram could be used to evaluate the prognosis of individual male GC patients. Further analysis showed that the prognostic model had an excellent predictive performance in both TCGA and validated cohorts. Besides, the result of tumor-infiltrating immune cell analysis indicated that the seven-IRGs signature could reflect the status of the tumor immune microenvironment.Conclusions: Our study developed a novel seven-IRGs risk signature for individualized survival prediction of male GC patients.

scholarly journals Identification and validation of a pyroptosis-related prognostic signature for thyroid cancer

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Pu Wu ◽  
Jinyuan Shi ◽  
Wei Sun ◽  
Hao Zhang
Keyword(s):  
Thyroid Cancer ◽  
Risk Score ◽  
Prognostic Model ◽  
Immune Cell ◽  
Cox Regression ◽  
Checkpoint Inhibitors ◽  
Risk Groups ◽  
Low Risk ◽  
Prognostic Signature ◽  
Cox Regression Analysis

Abstract Background Pyroptosis is a form of programmed cell death triggered by inflammasomes. However, the roles of pyroptosis-related genes in thyroid cancer (THCA) remain still unclear. Objective This study aimed to construct a pyroptosis-related signature that could effectively predict THCA prognosis and survival. Methods A LASSO Cox regression analysis was performed to build a prognostic model based on the expression profile of each pyroptosis-related gene. The predictive value of the prognostic model was validated in the internal cohort. Results A pyroptosis-related signature consisting of four genes was constructed to predict THCA prognosis and all patients were classified into high- and low-risk groups. Patients with a high-risk score had a poorer overall survival (OS) than those in the low-risk group. The area under the curve (AUC) of the receiver operator characteristic (ROC) curves assessed and verified the predictive performance of this signature. Multivariate analysis showed the risk score was an independent prognostic factor. Tumor immune cell infiltration and immune status were significantly higher in low-risk groups, which indicated a better response to immune checkpoint inhibitors (ICIs). Of the four pyroptosis-related genes in the prognostic signature, qRT-PCR detected three of them with significantly differential expression in THCA tissues. Conclusion In summary, our pyroptosis-related risk signature may have an effective predictive and prognostic capability in THCA. Our results provide a potential foundation for future studies of the relationship between pyroptosis and the immunotherapy response.

scholarly journals Integrated analysis of 1804 samples of six centers to construct and validate a robust immune-related prognostic signature associated with stromal cell abundance in tumor microenvironment for gastric cancer

2022 ◽  
Vol 20 (1) ◽  
Author(s):  
Junyu Huo ◽  
Ge Guan ◽  
Jinzhen Cai ◽  
Liqun Wu
Keyword(s):  
Gastric Cancer ◽  
Regression Analysis ◽  
Risk Score ◽  
Stromal Cell ◽  
Immune Cell ◽  
Cox Regression ◽  
Risk Group ◽  
Integrated Analysis ◽  
Prognostic Signature ◽  
Cox Regression Analysis

Abstract Background Stromal cells in tumor microenvironment could promote immune escape through a variety of mechanisms, but there are lacking research in the field of gastric cancer (GC). Methods We identified differential expressed immune-related genes (DEIRGs) between the high- and low-stromal cell abundance GC samples in The Cancer Genome Atlas and GSE84437 datasets. A risk score was constructed basing on univariate cox regression analysis, LASSO regression analysis, and multivariate cox regression analysis in the training cohort (n=772). The median value of the risk score was used to classify patients into groups with high and low risk. We conducted external validation of the prognostic signature in four independent cohorts (GSE26253, n=432; GSE62254, n=300; GSE15459, n=191; GSE26901, n=109) from the Gene Expression Omnibus (GEO) database. The immune cell infiltration was quantified by the CIBERSORT method. Results The risk score contained 6 genes (AKT3, APOD, FAM19A5, LTBP3, NOV, and NOX4) showed good performance in predicting 5-year overall survival (OS) rate and 5-year recurrence-free survival (RFS) rate of GC patients. The risk death and recurrence of GC patients growing with the increasing risk score. The patients were clustered into three subtypes according to the infiltration of 22 kinds of immune cells quantified by the CIBERSORT method. The proportion of cluster A with the worst prognosis in the high-risk group was significantly higher than that in the low-risk group; the risk score of cluster C subtype with the best prognosis was significantly lower than that of the other two subtypes. Conclusion This study established and validated a robust prognostic model for gastric cancer by integrated analysis 1804 samples of six centers, and its mechanism was explored in combination with immune cell infiltration characterization.

scholarly journals Development of a novel transcription factors-related prognostic signature for serous ovarian cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
He Li ◽  
Nayiyuan Wu ◽  
Zhao-Yi Liu ◽  
Yong-Chang Chen ◽  
Quan Cheng ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Transcription Factors ◽  
Risk Score ◽  
Cox Regression ◽  
Expression Profiles ◽  
Low Risk ◽  
Consensus Clustering ◽  
Serous Ovarian Cancer ◽  
Prognostic Signature ◽  
Significant Difference

AbstractGrowing evidence suggest that transcription factors (TFs) play vital roles in serous ovarian cancer (SOC). In the present study, TFs mRNA expression profiles of 564 SOC subjects in the TCGA database, and 70 SOC subjects in the GEO database were screened. A 17-TFs related prognostic signature was constructed using lasso cox regression and validated in the TCGA and GEO cohorts. Consensus clustering analysis was applied to establish a cluster model. The 17-TFs related prognostic signature, risk score and cluster models were effective at accurately distinguishing the overall survival of SOC. Analysis of genomic alterations were used to elaborate on the association between the 17-TFs related prognostic signature and genomic aberrations. The GSEA assay results suggested that there was a significant difference in the inflammatory and immune response pathways between the high-risk and low-risk score groups. The potential immune infiltration, immunotherapy, and chemotherapy responses were analyzed due to the significant difference in the regulation of lymphocyte migration and T cell-mediated cytotoxicity between the two groups. The results indicated that patients with low-risk score were more likely to respond anti-PD-1, etoposide, paclitaxel, and veliparib but not to gemcitabine, doxorubicin, docetaxel, and cisplatin. Also, the prognostic nomogram model revealed that the risk score was a good prognostic indicator for SOC patients. In conclusion, we explored the prognostic values of TFs in SOC and developed a 17-TFs related prognostic signature to predict the survival of SOC patients.

scholarly journals Transcription Elongation Factor A-like 7 is a Stemness-Related Prognostic Factor in Gastric Cancer

2021 ◽  
Author(s):  
Haisheng Qian ◽  
Xin Gao ◽  
Rui Ma ◽  
Wenjie Li ◽  
Zhen Yang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Regression Analysis ◽  
Cox Regression ◽  
Learning Algorithm ◽  
Cox Regression Analysis ◽  
Normal Tissues ◽  
Significant Difference ◽  
Selection Operator ◽  
Level Group

Abstract Background: Stemness is described as the potential for self-renewal and differentiation from the cell-of-origin. A previous study calculated the mRNA expression-based stemness index (mRNAsi) based on a one-class logistic regression machine learning algorithm for describing stemness features of cancer. We aim to identify stemness-related prognostic genes in gastric cancer (GC) based on mRNAsi using bioinformatics analysis.Methods: The WGCNA analysis was performed to find the relevant gene modules to mRNAsi. Gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathways annotation analysis were performed on genes in blue module. The overall survival analysis, univariate Cox regression analysis and the least absolute shrinkage and selection operator (LASSO) regression model were used to identify prognostic genes highly associated with survival. The multivariate Cox regression analysis was performed to analysis prognostic factors. The nomogram was constructed according to the result of multivariate analysis. qPCR, Western Blot and IHC staining were appliedResults: The mRNAsi of tumors is higher than normal tissues, and there was a significant difference in overall survival (OS) between the high and low mRNAsi GC groups. TCEAL7 was selected to be the key gene associated with mRNAsi and prognosis according to the result of least absolute shrinkage and selection operator (LASSO) Cox regression. The expression level of TCEAL7 was lower in tumors than in normal tissues, but high TCEAL7 level group showed a worse OS than low TCEAL7 level group in GC. Based on the result of multivariable Cox regression analysis which including TCEAL7 and clinical characteristics, a nomogram for predicting GC 1-, 3-, and 5-year survival was established. The C-index and the AUC (Area Under Curve) of the model indicated that the model has a good discrimination ability. Additionally, the calibration curves of 3- and 5-year OS rates showed the model fits well. The experimental validation of the expression of TCEAL7 in GC and normal tissues were consistent with the above.Conclusions: In summary, we verified mRNAsi was associated with the prognosis of GC patients. And TCEAL7 was finally identified as the key gene correlated with stemness features and prognosis in GC.

scholarly journals Development and Validation of a Robust Immune-Related Prognostic Signature for Gastric Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-24
Author(s):  
Junyu Huo ◽  
Liqun Wu ◽  
Yunjin Zang
Keyword(s):  
Gastric Cancer ◽  
High Risk ◽  
Risk Score ◽  
Cox Regression ◽  
Risk Group ◽  
Low Risk ◽  
M2 Macrophages ◽  
Regression Analyses ◽  
Prognostic Signature ◽  
Training Cohort

Background. An increasing number of reports have found that immune-related genes (IRGs) have a significant impact on the prognosis of a variety of cancers, but the prognostic value of IRGs in gastric cancer (GC) has not been fully elucidated. Methods. Univariate Cox regression analysis was adopted for the identification of prognostic IRGs in three independent cohorts (GSE62254, n = 300 ; GSE15459, n = 191 ; and GSE26901, n = 109 ). After obtaining the intersecting prognostic genes, the three independent cohorts were merged into a training cohort ( n = 600 ) to establish a prognostic model. The risk score was determined using multivariate Cox and LASSO regression analyses. Patients were classified into low-risk and high-risk groups according to the median risk score. The risk score performance was validated externally in the three independent cohorts (GSE26253, n = 432 ; GSE84437, n = 431 ; and TCGA, n = 336 ). Immune cell infiltration (ICI) was quantified by the CIBERSORT method. Results. A risk score comprising nine genes showed high accuracy for the prediction of the overall survival (OS) of patients with GC in the training cohort ( AUC > 0.7 ). The risk of death was found to have a positive correlation with the risk score. The univariate and multivariate Cox regression analyses revealed that the risk score was an independent indicator of the prognosis of patients with GC ( p < 0.001 ). External validation confirmed the universal applicability of the risk score. The low-risk group presented a lower infiltration level of M2 macrophages than the high-risk group ( p < 0.001 ), and the prognosis of patients with GC with a higher infiltration level of M2 macrophages was poor ( p = 0.011 ). According to clinical correlation analysis, compared with patients with the diffuse and mixed type of GC, those with the Lauren classification intestinal GC type had a significantly lower risk score ( p = 0.00085 ). The patients’ risk score increased with the progression of the clinicopathological stage. Conclusion. In this study, we constructed and validated a robust prognostic signature for GC, which may help improve the prognostic assessment system and treatment strategy for GC.

scholarly journals A signature of seven immune‐related genes predicts overall survival in male gastric cancer patients

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xin Xu ◽  
Yida Lu ◽  
Youliang Wu ◽  
Mingliang Wang ◽  
Xiaodong Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Overall Survival ◽  
Risk Score ◽  
Cox Regression ◽  
External Validation ◽  
The Cancer Genome Atlas ◽  
Differentially Expressed ◽  
Survival Prediction ◽  
Immune Related Genes

Abstract Background Gastric cancer (GC) has a high mortality rate and is one of the most fatal malignant tumours. Male sex has been proven as an independent risk factor for GC. This study aimed to identify immune-related genes (IRGs) associated with the prognosis of male GC. Methods RNA sequencing and clinical data were obtained from The Cancer Genome Atlas (TCGA) database. Differentially expressed IRGs between male GC and normal tissues were identified by integrated bioinformatics analysis. Univariate and multivariate Cox regression analyses were applied to screen survival-associated IRGs. Then, GC patients were separated into high- and low-risk groups based on the median risk score. Furthermore, a nomogram was constructed based on the TCGA dataset. The prognostic value of the risk signature model was evaluated by Kaplan-Meier curve, receiver operating characteristic (ROC), Harrell’s concordance index and calibration curves. In addition, the gene expression dataset from the Gene Expression Omnibus (GEO) was also downloaded for external validation. The relative proportions of 22 types of infiltrating immune cells in each male GC sample were evaluated using CIBERSORT. Results A total of 276 differentially expressed IRGs were screened, including 189 up-regulated and 87 down-regulated genes. Subsequently, a seven-IRGs signature (LCN12, CCL21, RNASE2, CGB5, NRG4, AGTR1 and NPR3) was identified to be significantly associated with the overall survival (OS) of male GC patients. Survival analysis indicated that patients in the high-risk group exhibited a poor clinical outcome. The results of multivariate analysis revealed that the risk score was an independent prognostic factor. The established nomogram could be used to evaluate the prognosis of individual male GC patients. Further analysis showed that the prognostic model had excellent predictive performance in both TCGA and validated cohorts. Besides, the results of tumour-infiltrating immune cell analysis indicated that the seven-IRGs signature could reflect the status of the tumour immune microenvironment. Conclusions Our study developed a novel seven-IRGs risk signature for individualized survival prediction of male GC patients.

scholarly journals Development of a novel transcription factors-related prognostic signature for serous ovarian cancer

2020 ◽  
Author(s):  
He Li ◽  
Zhao-Yi Liu ◽  
Nayiyuan Wu ◽  
Yong-Chang Chen ◽  
Quan Cheng ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Transcription Factors ◽  
Risk Score ◽  
Clustering Analysis ◽  
Cox Regression ◽  
Low Risk ◽  
Consensus Clustering ◽  
Serous Ovarian Cancer ◽  
Prognostic Signature ◽  
Significant Difference

Abstract BackgroundOvarian cancer (OC) is one of the most lethal gynecological cancer globally. Serous ovarian cancer (SOC) is most common pathological type of ovarian cancer. Growing evidence suggests that transcription factors (TFs) play vital roles in serous ovarian cancer (SOC). In the present study, we aimed to develop a transcription factors-related prognostic signature to better predict the survival in patients with SOC.Materials and methodsThe TFs mRNA expression profiles of 564 SOC subjects in the TCGA database, and 70 SOC subjects in the GEO database were screened. Lasso cox regression and consensus clustering analysis were utilized to construct a novel TFs related signature and cluster model, respectively. Genomic alternative analysis was used to elaborate on the association between the TFs related prognostic signature and genomic aberrations. GSEA analysis was applied to identify the biological functional difference between high risk-score group and low-risk score group.ResultsA 17-TFs related prognostic signature was constructed using lasso cox regression and validated in the TCGA and GEO cohorts. Consensus clustering analysis was applied to establish a cluster model. The 17-TFs related prognostic signature, risk score, and cluster models were effective at accurately distinguishing the prognosis of SOC. The GSEA assay results suggested that there was a significant difference in the inflammatory and immune response pathways between the high-risk and low-risk score groups. Immune infiltration, immunotherapy, and chemotherapy responses were analyzed due to the significant difference in the regulation of lymphocyte migration and T cell-mediated cytotoxicity between the two groups; indicating that patients with low-risk score were more likely to respond anti-PD-1, etoposide, paclitaxel, and veliparib but not to gemcitabine, doxorubicin, docetaxel, and cisplatin. Also, the prognostic nomogram model revealed that the risk score was a good prognostic indicator for SOC patients.ConclusionsIn conclusion, we explored the prognostic values of TFs in SOC and developed a 17-TFs related prognostic signature to predict the survival of SOC patients.

scholarly journals A signature of 24 aging‑related gene pairs predict overall survival in gastric cancer

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Yankai Zhang ◽  
Yichao Yan ◽  
Ning Ning ◽  
Zhanlong Shen ◽  
Yingjiang Ye
Keyword(s):  
Gastric Cancer ◽  
Regression Analysis ◽  
High Risk ◽  
Operating Characteristic ◽  
Cox Regression ◽  
Risk Group ◽  
Low Risk ◽  
Related Gene ◽  
Prognostic Signature ◽  
Cox Regression Analysis

Abstract Background Aging is the major risk factor for most human cancers. We aim to develop and validate a reliable aging-related gene pair signature (ARGPs) to predict the prognosis of gastric cancer (GC) patients. Methods The mRNA expression data and clinical information were obtained from two public databases, The Cancer Genome Atlas (TCGA) dataset, and Gene Expression Omnibus (GEO) dataset, respectively. The best prognostic signature was established using Cox regression analysis (univariate and least absolute shrinkage and selection operator). The optimal cut-off value to distinguish between high- and low-risk patients was found by time-dependent receiver operating characteristic (ROC). The prognostic ability of the ARGPS was evaluated by a log‐rank test and a Cox proportional hazards regression model. Results The 24 ARGPs were constructed for GC prognosis. Using the optimal cut-off value − 0.270, all patients were stratified into high risk and low risk. In both TCGA and GEO cohorts, the results of Kaplan–Meier analysis showed that the high-risk group has a poor prognosis (P < 0.001, P = 0.002, respectively). Then, we conducted a subgroup analysis of age, gender, grade and stage, and reached the same conclusion. After adjusting for a variety of clinical and pathological factors, the results of multivariate COX regression analysis showed that the ARGPs is still an independent prognostic factor of OS (HR, 4.919; 95% CI 3.345–7.235; P < 0.001). In comparing with previous signature, the novel signature was superior, with an area under the receiver operating characteristic curve (AUC) value of 0.845 vs. 0.684 vs. 0.695. The results of immune infiltration analysis showed that the abundance of T cells follicular helper was significantly higher in the low-risk group, while the abundance of monocytes was the opposite. Finally, we identified and incorporated independent prognostic factors and developed a superior nomogram to predict the prognosis of GC patients. Conclusion Our study has developed a robust prognostic signature that can accurately predict the prognostic outcome of GC patients.

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