scholarly journals Identification of an immune gene signature for predicting the prognosis of patients with uterine corpus endometrial carcinoma

2020 ◽  
Author(s):  
Cankun Zhou ◽  
Chaomei Li ◽  
Fangli Yan ◽  
Yuhua Zheng
Keyword(s):  
Endometrial Carcinoma ◽  
Risk Score ◽  
Prognostic Model ◽  
Immune Cell ◽  
Gene Signature ◽  
Cancer Genome ◽  
Functional Enrichment ◽  
Immune Gene ◽  
Uterine Corpus ◽  
Immune Genes

Abstract Background: Uterine corpus endometrial carcinoma (UCEC) is a frequent gynecological malignancy with a poor prognosis especially when at an advanced stage. In the present study, we explored the potential of an immune-related gene signature to predict overall survival in UCEC patients.Methods: We analyzed expression data of 616 UCEC patients from The Cancer Genome Atlas database and the International Cancer Genome Consortium as well as immune genes from the ImmPort database and identified the signature. We constructed a transcription factor regulatory network based on Cistrome databases and performed functional enrichment and pathway analyses for the differentially expressed immune genes. Moreover, the prognostic value of 410 immune genes was determined using Cox regression analysis then constructed a prognostic model. Finally, we performed immune infiltration analysis using TIMER-generating immune cell content.Results: Results indicated that the immune cell microenvironment as well as the PI3K-Akt, and MARK signaling pathways were involved in UCEC development. The established prognostic model revealed a ten-gene prognosis signature , comprising PDIA3, LTA, PSMC4, TNF, SBDS, HDGF, HTR3E, NR3C1, PGR, and CBLC . This can be used as an independent tool to predict the prognosis of UCEC owing to the observed risk-score. In addition, levels of B cells and neutrophils were significantly correlated with the patient's risk score, and the expression of ten genes is associated with immune cell infiltrates.Conclusions: In summary, we present a 10-gene signature with the potential to predict the prognosis of UCEC. This is expected to guide future development of individualized treatment approaches.

scholarly journals Identification of an immune gene signature with prognostic value for patients with uterine corpus endometrial carcinoma

2020 ◽  
Author(s):  
Cankun Zhou ◽  
Chaomei Li ◽  
Fangli Yan ◽  
Yuhua Zheng
Keyword(s):  
Regression Analysis ◽  
Endometrial Carcinoma ◽  
Prognostic Value ◽  
Prognostic Model ◽  
Immune Cell ◽  
Cox Regression ◽  
Gene Signature ◽  
Immune Gene ◽  
Cox Regression Analysis ◽  
Immune Genes

Abstract Background: Uterine corpus endometrial carcinoma (UCEC) is a very common gynecological malignancy with a poor prognosis in the late stage. Therefore, the purpose of this study was to determine an immune-related gene signature that predicts the patients’ OS for UCEC. Methods: Based on TCGA, ImmPort, and Cistrome databases, the differential immune genes were screened and the TFs regulatory network was constructed. Functional enrichment and pathway analysis of differential immune genes were carried out. Prognostic value of 410 immune genes was analyzed by Cox regression analysis, a prognostic model was constructed, ROC curves were used to verify the accuracy of the model, and independent prognostic analysis was performed. Finally, the immune cell content was obtained by TIMER, and the correlation with the immune gene expression was evaluated by univariate Cox regression analysis. Results: It was found that the immune cell microenvironment and PI3K-Akt, MARK signaling pathways were involved in the development of UCEC. Based on the established prognostic model, ten-gene prognosis signature (PDIA3, LTA, PSMC4, TNF, SBDS, HDGF, HTR3E, NR3C1, PGR, CBLC) for UCEC prognostic prediction were finally identified, and our study has shown that risk-score can be a powerful prognostic factor for UCEC, independent of other clinical factors. The levels of B cells and neutrophils may be significantly correlated with the patient's risk score. Conclusions: Our studies showed that the ten-gene prognosis signature had important clinical value for the prognosis of UCEC, which was helpful for individualized treatment and provided a new target for tumor immunotherapy.

scholarly journals Identification of an immune gene signature for predicting the prognosis of patients with uterine corpus endometrial carcinoma

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Cankun Zhou ◽  
Chaomei Li ◽  
Fangli Yan ◽  
Yuhua Zheng
Keyword(s):  
Endometrial Carcinoma ◽  
Immune Cell ◽  
Cox Regression ◽  
The Cancer Genome Atlas ◽  
Functional Enrichment ◽  
Immune Gene ◽  
Prognostic Signature ◽  
Cox Regression Analysis ◽  
Uterine Corpus ◽  
Immune Genes

Abstract Background Uterine corpus endometrial carcinoma (UCEC) is a frequent gynecological malignancy with a poor prognosis particularly at an advanced stage. Herein, this study aims to construct prognostic markers of UCEC based on immune-related genes to predict the prognosis of UCEC. Methods We analyzed expression data of 575 UCEC patients from The Cancer Genome Atlas database and immune genes from the ImmPort database, which were used for generation and validation of the signature. We constructed a transcription factor regulatory network based on Cistrome databases, and also performed functional enrichment and pathway analyses for the differentially expressed immune genes. Moreover, the prognostic value of 410 immune genes was determined using the Cox regression analysis. We then constructed and verified a prognostic signature. Finally, we performed immune infiltration analysis using TIMER-generating immune cell content. Results The immune cell microenvironment as well as the PI3K-Akt, and MARK signaling pathways were involved in UCEC development. The established prognostic signature revealed a ten-gene prognostic signature, comprising of PDIA3, LTA, PSMC4, TNF, SBDS, HDGF, HTR3E, NR3C1, PGR, and CBLC. This signature showed a strong prognostic ability in both the training and testing sets and thus can be used as an independent tool to predict the prognosis of UCEC. In addition, levels of B cells and neutrophils were significantly correlated with the patient’s risk score, while the expression of ten genes was associated with immune cell infiltrates. Conclusions In summary, the ten-gene prognostic signature may guide the selection of the immunotherapy for UCEC.

scholarly journals Identification of an immune gene signature for predicting the prognosis of patients with uterine corpus endometrial carcinoma

2020 ◽  
Author(s):  
Cankun Zhou ◽  
Chaomei Li ◽  
Fangli Yan ◽  
Yuhua Zheng
Keyword(s):  
Endometrial Carcinoma ◽  
Immune Cell ◽  
Cox Regression ◽  
The Cancer Genome Atlas ◽  
Functional Enrichment ◽  
Immune Gene ◽  
Prognostic Signature ◽  
Cox Regression Analysis ◽  
Uterine Corpus ◽  
Immune Genes

Abstract Background: Uterine corpus endometrial carcinoma (UCEC) is a frequent gynecological malignancy with a poor prognosis particularly at an advanced stage. Herein, this study aims to construct prognostic markers of UCEC based on immune-related genes to predict the prognosis of UCEC.Methods: We analyzed expression data of 575 UCEC patients from The Cancer Genome Atlas database and immune genes from the ImmPort database, which were used for generation and validation of the signature. We constructed a transcription factor regulatory network based on Cistrome databases, and also performed functional enrichment and pathway analyses for the differentially expressed immune genes. Moreover, the prognostic value of 410 immune genes was determined using the Cox regression analysis. We then constructed and verified a prognostic signature. Finally, we performed immune infiltration analysis using TIMER-generating immune cell content.Results: The immune cell microenvironment as well as the PI3K-Akt, and MARK signaling pathways were involved in UCEC development. The established prognostic signature revealed a ten-gene prognostic signature, comprising of PDIA3, LTA, PSMC4, TNF, SBDS, HDGF, HTR3E, NR3C1, PGR, and CBLC. This signature showed a strong prognostic ability in both the training and testing sets and thus can be used as an independent tool to predict the prognosis of UCEC. In addition, levels of B cells and neutrophils were significantly correlated with the patient's risk score, while the expression of ten genes was associated with immune cell infiltrates.Conclusions: In summary, the ten-gene prognostic signature may guide the selection of the immunotherapy for UCEC.

scholarly journals Hypoxia-Related Immune Gene Signature Predicting Prognosis in Patients With Hepatocellular Carcinoma

2021 ◽  
Author(s):  
Lingshan Zhou ◽  
Yuan Yang ◽  
Min Liu ◽  
Rong Liu ◽  
Man Ren ◽  
...  
Keyword(s):  
Immune Cell ◽  
Cox Regression ◽  
Biological Significance ◽  
Gene Signature ◽  
Chemotherapeutic Agents ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Functional Enrichment ◽  
Immune Gene ◽  
Consensus Clustering

Abstract BackgroundHepatocellular carcinoma (HCC) remains a global health challenge. Increasing evidence indicates that hypoxia is crucial in the evolution and progression of HCC by regulating the tumor immune microenvironment. The present study aimed to construct a prognostic relevant hypoxia-related immune gene (HRIG) signature. MethodsWe analyzed the expression profile of the 163 HRIGs and clinical information of 371 patients with HCC obtained from The Cancer Genome Atlas (TCGA). Then, consensus clustering analysis was performed to divide HCC patients into clusters 1 and 2 based on the HRIG expression. Subsequently, A multigene signature was constructed by Least absolute shrinkage and selection operator (LASSO) Cox regression analyses. Then, we evaluated the prognostic capability of this signature by Kaplan-Meier analysis, univariate Cox regression and multivariate Cox regression. The prognostic value of the signature was validated in the International Cancer Genome Consortium (ICGC) database. Furthermore, the functional enrichment analyses were preformed to elucidate their biological significance. Finally, we evaluated the infiltration of immune cells and the sensitivity of administrating chemotherapeutic agents.ResultsA total of 37 prognosis-related HRIGs were obtained. Subsequently, we constructed an 8-gene signature on the basis of prognosis-related HRIGs, which had a good performance in predicting the overall survival of patients with HCC. In addition, the signature expressed robust when validated in ICGC. The results revealed that these genes involved in some of the HCC-related pathways and was associated with the infiltration of immune cell subtypes. More importantly, the identified model was linked to the sensitivity of some chemotherapeutic agents. ConclusionsHRIG signature is an effective predictor for the prognosis of patients with HCC.

scholarly journals Identification of the prognostic value of a 2-gene signature of the WNT gene family in UCEC using bioinformatics and real-world data

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yuexin Hu ◽  
Mingjun Zheng ◽  
Dandan Zhang ◽  
Rui Gou ◽  
Ouxuan Liu ◽  
...  
Keyword(s):  
Gene Family ◽  
Endometrial Carcinoma ◽  
Clinical Features ◽  
Risk Score ◽  
Real World ◽  
Prognostic Value ◽  
Gene Signature ◽  
Real World Data ◽  
Uterine Corpus ◽  
World Data

Abstract Background The WNT gene family plays an important role in the occurrence and development of malignant tumors, but its involvement has not been systematically analyzed in uterine corpus endometrial carcinoma (UCEC). This study aimed to evaluate the prognostic value of the WNT gene family in UCEC. Methods Pan-cancer transcriptome data of the UCSC Xena database and Genotype-Tissue Expression (GTEx) normal tissue data were downloaded to analyze the expression and prognosis of 19 WNT family genes in UCEC. A cohort from The Cancer Genome Atlas-Uterine Corpus Endometrial Carcinoma (TCGA-UCEC) was used to analyze the expression of the WNT gene family in different immune subtypes and clinical subgroups. The STRING database was used to analyze the interaction of the WNT gene family and its biological function. Univariate Cox regression analysis and Lasso cox analysis were used to identify the genes associated with significant prognosis and to construct multi signature prognosis model. An immunohistochemical assay was used to verify the predictive ability of the model. Risk score and the related clinical features were used to construct a nomogram. Results The expression levels of WNT2, WNT3, WNT3A, WNT5A, WNT7A, and WNT10A were significantly different among different immune subtypes and correlated with TP53 mutation. According to the WNT family genes related to the prognosis of UCEC, UCEC was classified into two subtypes (C1, C2). The prognosis of subtype C1 was significantly better than that of subtype C2. A 2-gene signature (WNT2 and WNT10A) was constructed and the two significantly prognostic groups can be divided based on median Risk score. These results were verified using real-world data, and the nomogram constructed using clinical features and Risk score had good prognostic ability. Conclusions The 2-gene signature including WNT2 and WNT10A can be used to predict the prognosis of patients with UCEC, which is important for clinical decision-making and individualized therapy for patients with UCEC.

scholarly journals Construction and Validation of a Prognostic Gene-Based Model for Overall Survival Prediction in Hepatocellular Carcinoma Using an Integrated Statistical and Bioinformatic Approach

2021 ◽  
Vol 22 (4) ◽  
pp. 1632
Author(s):  
Eskezeia Yihunie Dessie ◽  
Siang-Jyun Tu ◽  
Hui-Shan Chiang ◽  
Jeffrey J.P. Tsai ◽  
Ya-Sian Chang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
High Risk ◽  
Risk Score ◽  
Prognostic Model ◽  
Gene Signature ◽  
Adaptive Lasso ◽  
Functional Enrichment ◽  
Survival Prediction ◽  
Prognostic Gene ◽  
Prognostic Gene Signature

Hepatocellular carcinoma (HCC) is one of the most common lethal cancers worldwide and is often related to late diagnosis and poor survival outcome. More evidence is demonstrating that gene-based prognostic models can be used to predict high-risk HCC patients. Therefore, our study aimed to construct a novel prognostic model for predicting the prognosis of HCC patients. We used multivariate Cox regression model with three hybrid penalties approach including least absolute shrinkage and selection operator (Lasso), adaptive lasso and elastic net algorithms for informative prognostic-related genes selection. Then, the best subset regression was used to identify the best prognostic gene signature. The prognostic gene-based risk score was constructed using the Cox coefficient of the prognostic gene signature. The model was evaluated by Kaplan–Meier (KM) and receiver operating characteristic curve (ROC) analyses. A novel four-gene signature associated with prognosis was identified and the risk score was constructed based on the four-gene signature. The risk score efficiently distinguished the patients into a high-risk group with poor prognosis. The time-dependent ROC analysis revealed that the risk model had a good performance with an area under the curve (AUC) of 0.780, 0.732, 0.733 in 1-, 2- and 3-year prognosis prediction in The Cancer Genome Atlas (TCGA) dataset. Moreover, the risk score revealed a high diagnostic performance to classify HCC from normal samples. The prognosis and diagnosis prediction performances of risk scores were verified in external validation datasets. Functional enrichment analysis of the four-gene signature and its co-expressed genes involved in the metabolic and cell cycle pathways was constructed. Overall, we developed a novel-gene-based prognostic model to predict high-risk HCC patients and we hope that our findings can provide promising insight to explore the role of the four-gene signature in HCC patients and aid risk classification.

scholarly journals Comprehensive Analysis to Identify the Epithelial–Mesenchymal Transition-Related Immune Signatures as a Prognostic and Therapeutic Biomarkers in Hepatocellular Carcinoma

2021 ◽  
Vol 8 ◽  
Author(s):  
Guozhi Wu ◽  
Yuan Yang ◽  
Yu Zhu ◽  
Yemao Li ◽  
Zipeng Zhai ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
High Risk ◽  
Risk Score ◽  
Prognostic Model ◽  
Risk Model ◽  
Cox Regression ◽  
Epithelial Mesenchymal Transition ◽  
Cancer Genome ◽  
Mesenchymal Transition ◽  
Immune Genes

Background: Hepatocellular carcinoma (HCC) is a highly heterogeneous disease with the high rates of the morbidity and mortality due to the lack of the effective prognostic model for prediction.Aim: To construct a risk model composed of the epithelial–mesenchymal transition (EMT)-related immune genes for the assessment of the prognosis, immune infiltration status, and chemosensitivity.Methods: We obtained the transcriptome and clinical data of the HCC samples from The Cancer Genome Atlas (TCGA) and The International Cancer Genome Consortium (ICGC) databases. The Pearson correlation analysis was applied to identify the differentially expressed EMT-related immune genes (DE-EMTri-genes). Subsequently, the univariate Cox regression was introduced to screen out the prognostic gene sets and a risk model was constructed based on the least absolute shrinkage and selection operator-penalized Cox regression. Additionally, the receiver operating characteristic (ROC) curves were plotted to compare the prognostic value of the newly established model compared with the previous model. Furthermore, the correlation between the risk model and survival probability, immune characteristic, and efficacy of the chemotherapeutics were analyzed by the bioinformatics methods.Results: Six DE-EMTri-genes were ultimately selected to construct the prognostic model. The area under the curve (AUC) values for 1-, 2-, and 3- year were 0.773, 0.721, and 0.673, respectively. Stratified survival analysis suggested that the prognosis of the low-score group was superior to the high-score group. Moreover, the univariate and multivariate analysis indicated that risk score [hazard ratio (HR) 5.071, 95% CI 3.050, 8.432; HR 4.396, 95% CI 2.624, 7.366; p < 0.001] and stage (HR 2.500, 95% CI 1.721, 3.632; HR 2.111, 95% CI 1.443, 3.089; p < 0.001) served as an independent predictive factors in HCC. In addition, the macrophages, natural killer (NK) cells, and regulatory T (Treg) cells were significantly enriched in the high-risk group. Finally, the patients with the high-risk score might be more sensitive to cisplatin, doxorubicin, etoposide, gemcitabine, and mitomycin C.Conclusion: We established a reliable EMTri-genes-based prognostic signature, which may hold promise for the clinical prediction.

Identification of prognosis-associated immune genes and exploration of immune cell infiltration in colorectal cancer

2020 ◽  
Vol 14 (14) ◽  
pp. 1353-1369
Author(s):  
Yan-Dong Miao ◽  
Jiang-Tao Wang ◽  
Yuan Yang ◽  
Xue-Ping Ma ◽  
Deng-Hai Mi
Keyword(s):  
Colorectal Cancer ◽  
Risk Score ◽  
Prognostic Model ◽  
Immune Cell ◽  
Expression Profiles ◽  
Clinical Stage ◽  
The Cancer Genome Atlas ◽  
Immune Genes ◽  
Prognosis Model ◽  
Cancer Genome Atlas

Aim: To identify prognosis-related immune genes (PRIGs) and construct a prognosis model of colorectal cancer (CRC) patients for clinical use. Materials & methods: Expression profiles were obtained from The Cancer Genome Atlas database and identified differentially expressed PRIGs of CRC. Results: A prognostic model was conducted based on nine PRIGs. The risk score, based on prognosis model, was an independent prognostic predictor. Five PRIGs and risk score were significantly associated with the clinical stage of CRC and five immune cells related to the risk score. Conclusion: The risk score was an independent prognostic biomarker for CRC patients. The research excavated immune genes that were associated with survival and that could be potential biomarkers for prognosis and treatment for CRC patients.

scholarly journals Identification of a Prognostic Six-Immune-Gene Signature and a Nomogram Model for Uveal Melanoma

2022 ◽  
Author(s):  
Binghua Yang ◽  
Yuxia Fan ◽  
Renlong Liang ◽  
Yi Wu ◽  
Aiping Gu
Keyword(s):  
High Risk ◽  
Uveal Melanoma ◽  
Risk Score ◽  
Risk Group ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Gene Signature ◽  
Functional Enrichment ◽  
Immune Gene ◽  
Prognostic Signature

Abstract Background: To identify an immune-related prognostic signature and find potential therapeutic targets for uveal melanoma. Methods: The RNA-sequencing data obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. The prognostic six-immune-gene signature was constructed through least absolute shrinkage and selection operator and multi-variate Cox regression analyses. Functional enrichment analysis and single sample GSEA were carried out. In addition, a nomogram model established by integrating clinical variables and this signature risk score was also constructed and evaluated.Results: We obtained 130 prognostic immune genes, and six of them were selected to construct a prognostic signature in the TCGA uveal melanoma dataset. Patients were classified into high-risk and low-risk groups according to a median risk score of this signature. High-risk group patients had poorer overall survival in comparison to the patients in the low-risk group (p < 0.001). These findings were further validated in two external GEO datasets. A nomogram model proved to be a good classifier for uveal melanoma by combining this signature. Both functional enrichment analysis and single sample GSEA analysis verified that this signature was truly correlated with immune system. In addition, in vitro cell experiments results demonstrated the consistent trend of our computational findings.Conclusion: Our newly identified six-immune-gene signature and a nomogram model could be used as meaningful prognostic biomarkers, which might provide uveal melanoma patients with individualized clinical prognosis prediction and potential novel treatment targets.

scholarly journals Identification of an Individualized Immune-Related Prognostic Risk Score in Lung Squamous Cell Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Yuan Zhuang ◽  
Sihan Li ◽  
Chang Liu ◽  
Guang Li
Keyword(s):  
Risk Score ◽  
Squamous Cell ◽  
Cell Cancer ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Functional Enrichment ◽  
Immune Gene ◽  
Cox Regression Analysis ◽  
Cancer Genome Atlas ◽  
Genome Atlas

Background: Lung squamous cell carcinoma (LUSC) is one of the most common histological subtypes of non-small cell lung cancer (NSCLC), and its morbidity and mortality are steadily increasing. The purpose of this study was to study the relationship between the immune-related gene (IRGs) profile and the outcome of LUSC in patients by analyzing datasets from The Cancer Genome Atlas (TCGA).Methods: We obtained publicly available LUSC RNA expression data and clinical survival data from The Cancer Genome Atlas (TCGA), and filtered IRGs based on The ImmPort database. Then, we identified risk immune-related genes (r-IRGs) for model construction using Cox regression analysis and defined the risk score in this model as the immune gene risk index (IRI). Multivariate analysis was used to verify the independent prognostic value of IRI and its association with other clinicopathological features. Pearson correlation analysis was used to explore the molecular mechanism affecting the expression of IRGs and the correlation between IRI and immune cell infiltration.Results: We screened 15 r-IRGs for constructing the risk model. The median value of IRI stratified the patients and there were significant survival differences between the two groups (p = 4.271E-06). IRI was confirmed to be an independent prognostic factor (p &lt; 0.001) and had a close correlation with the patients' age (p &lt; 0.05). Interestingly, the infiltration of neutrophils or dendritic cells was strongly upregulated in the high-IRI groups (p &lt; 0.05). Furthermore, by investigating differential transcription factors (TFs) and functional enrichment analysis, we explored potential mechanisms that may affect IRGs expression in tumor cells.Conclusion: In short, this study used 15 IRGs to build an effective risk prediction model, and demonstrated the significance of IRGs-based personalized immune scores in LUSC prognosis.

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