scholarly journals Comprehensive Analysis of Ferroptosis-Related LncRNAs in Breast Cancer Patients Reveals Prognostic Value and Relationship With Tumor Immune Microenvironment

2021 ◽  
Vol 8 ◽  
Author(s):  
Zhengjie Xu ◽  
Suxiao Jiang ◽  
Juan Ma ◽  
Desheng Tang ◽  
Changsheng Yan ◽  
...  

Background: Breast cancer (BC) is a heterogeneous malignant tumor, leading to the second major cause of female mortality. This study aimed to establish an in-depth relationship between ferroptosis-related LncRNA (FRlncRNA) and the prognosis as well as immune microenvironment of the patients with BC.Methods: We downloaded and integrated the gene expression data and the clinical information of the patients with BC from The Cancer Genome Atlas (TCGA) database. The co-expression network analysis and univariate Cox regression analysis were performed to screen out the FRlncRNAs related to prognosis. A cluster analysis was adopted to explore the difference of immune microenvironment between the clusters. Furthermore, we determined the optimal survival-related FRLncRNAs for final signature by LASSO Cox regression analysis. Afterward, we constructed and validated the prediction models, which were further tested in different subgroups.Results: A total of 31 FRLncRNAs were filtrated as prognostic biomarkers. Two clusters were determined, and C1 showed better prognosis and higher infiltration level of immune cells, such as B cells naive, plasma cells, T cells CD8, and T cells CD4 memory activated. However, there were no significantly different clinical characters between the clusters. Gene Set Enrichment Analysis (GSEA) revealed that some metabolism-related pathways and immune-associated pathways were exposed. In addition, 12 FRLncRNAs were determined by LASSO analysis and used to construct a prognostic signature. In both the training and testing sets, patients in the high-risk group had a worse survival than the low-risk patients. The area under the curves (AUCs) of receiver operator characteristic (ROC) curves were about 0.700, showing positive prognostic capacity. More notably, through the comprehensive analysis of heatmap, we regarded LINC01871, LINC02384, LIPE-AS1, and HSD11B1-AS1 as protective LncRNAs, while LINC00393, AC121247.2, AC010655.2, LINC01419, PTPRD-AS1, AC099329.2, OTUD6B-AS1, and LINC02266 were classified as risk LncRNAs. At the same time, the patients in the low-risk groups were more likely to be assigned to C1 and had a higher immune score, which were consistent with a better prognosis.Conclusion: Our research indicated that the ferroptosis-related prognostic signature could be used as novel biomarkers for predicting the prognosis of BC. The differences in the immune microenvironment exhibited by BC patients with different risks and clusters suggested that there may be a complementary synergistic effect between ferroptosis and immunotherapy.

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiaoping Li ◽  
Jishang Chen ◽  
Qihe Yu ◽  
Hui Huang ◽  
Zhuangsheng Liu ◽  
...  

Background: A surge in newly diagnosed breast cancer has overwhelmed the public health system worldwide. Joint effort had beed made to discover the genetic mechanism of these disease globally. Accumulated research has revealed autophagy may act as a vital part in the pathogenesis of breast cancer.Objective: Aim to construct a prognostic model based on autophagy-related lncRNAs and investigate their potential mechanisms in breast cancer.Methods: The transcriptome data and clinical information of patients with breast cancer were obtained from The Cancer Genome Atlas (TCGA) database. Autophagy-related genes were obtained from the Human Autophagy Database (HADb). Long non-coding RNAs (lncRNAs) related to autophagy were acquired through the Pearson correlation analysis. Univariate Cox regression analysis as well as the least absolute shrinkage and selection operator (LASSO) regression analysis were used to identify autophagy-related lncRNAs with prognostic value. We constructed a risk scoring model to assess the prognostic significance of the autophagy-related lncRNAs signatures. The nomogram was then established based on the risk score and clinical indicators. Through the calibration curve, the concordance index (C-index) and receiver operating characteristic (ROC) curve analysis were evaluated to obtain the model's predictive performance. Subgroup analysis was performed to evaluate the differential ability of the model. Subsequently, gene set enrichment analysis was conducted to investigate the potential functions of these lncRNAs.Results: We attained 1,164 breast cancer samples from the TCGA database and 231 autophagy-related genes from the HAD database. Through correlation analysis, 179 autophagy-related lncRNAs were finally identified. Univariate Cox regression analysis and LASSO regression analysis further screened 18 prognosis-associated lncRNAs. The risk scoring model was constructed to divide patients into high-risk and low-risk groups. It was found that the low-risk group had better overall survival (OS) than those of the high-risk group. Then, the nomogram model including age, tumor stage, TNM stage and risk score was established. The evaluation index (C-index: 0.78, 3-year OS AUC: 0.813 and 5-year OS AUC: 0.785) showed that the nomogram had excellent predictive power. Subgroup analysis showed there were difference in OS between high-risk and low-risk patients in different subgroups (stage I-II, ER positive, Her-2 negative and non-TNBC subgroups; all P < 0.05). According to the results of gene set enrichment analysis, these lncRNAs were involved in the regulation of multicellular organismal macromolecule metabolic process in multicellular organisms, nucleotide excision repair, oxidative phosphorylation, and TGF-β signaling pathway.Conclusions: We identified 18 autophagy-related lncRNAs with prognostic value in breast cancer, which may regulate tumor growth and progression in multiple ways.


2021 ◽  
Author(s):  
Zhehong Li ◽  
Junqiang Wei ◽  
Honghong Zheng ◽  
Xintian Gan ◽  
Mingze Song ◽  
...  

Abstract Background: Hypoxia- and immune-status play an essential role in tumorigenesis and tumor development. This study sought to build a novel hypoxia- and immune-related signature to evaluate sarcoma patients' prognosis.Methods: Transcriptome data and clinicopathological characteristics of sarcoma patients were downloaded from the TARGET database. We grouped patients with three clusters by using t-SNE. We defined the three cluster as high-, medium-, and low-hypoxia clusters by K-M analysis and differential expression of target genes associated with the HIF-1 signaling pathway. Then we used the "limma" package to screen hypoxia-related differentially expressed genes (HRDEGs) in the high- and low-hypoxia clusters. We immediately assessed the immune status by using the single sample Gene Set Enrichment Analysis (ssGSEA) and divided the patients into high-, medium-, and low-immune clusters. Immune-related DEGs (IRDEGs) were filtered in the high- and low- immune groups. The intersection of HRDEGs and IRDEGs screened overlapping genes. We used a combination of Cox regression analysis and LASSO model to obtain prognosis-related genes and established a novel hypoxia- and immune-related prognostic signature for sarcoma patients. Combining clinicopathological characteristics of sarcoma patients, we evaluated the signature by univariate and multivariate Cox regression analysis. We further divided the patients into high- and low-risk groups based on the novel signature. Finally, we evaluated the differences in hypoxia status and the immune status in high- and low-risk groups.Results: We identified two genes associated with prognosis, CMA1 and IGDCC3. The novel Prognostic signature could be used as an independent prognostic factor for sarcoma patients. We distinguished patients more effectively by their different survival outcomes, immune cells' infiltration status, and immune-related markers.Conclusion: The hypoxia- and immune-related prognostic signature can be used to stratify the risk of sarcoma patients. Our study established a new prognostic signature and provides a potential prognostic markers for hypoxia- and immune-related therapy.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Lin Chen ◽  
Yuxiang Dong ◽  
Yitong Pan ◽  
Yuhan Zhang ◽  
Ping Liu ◽  
...  

Abstract Background Breast cancer is one of the main malignant tumors that threaten the lives of women, which has received more and more clinical attention worldwide. There are increasing evidences showing that the immune micro-environment of breast cancer (BC) seriously affects the clinical outcome. This study aims to explore the role of tumor immune genes in the prognosis of BC patients and construct an immune-related genes prognostic index. Methods The list of 2498 immune genes was obtained from ImmPort database. In addition, gene expression data and clinical characteristics data of BC patients were also obtained from the TCGA database. The prognostic correlation of the differential genes was analyzed through Survival package. Cox regression analysis was performed to analyze the prognostic effect of immune genes. According to the regression coefficients of prognostic immune genes in regression analysis, an immune risk scores model was established. Gene set enrichment analysis (GSEA) was performed to probe the biological correlation of immune gene scores. P < 0.05 was considered to be statistically significant. Results In total, 556 immune genes were differentially expressed between normal tissues and BC tissues (p < 0. 05). According to the univariate cox regression analysis, a total of 66 immune genes were statistically significant for survival risk, of which 30 were associated with overall survival (P < 0.05). Finally, a 15 immune genes risk scores model was established. All patients were divided into high- and low-groups. KM survival analysis revealed that high immune risk scores represented worse survival (p < 0.001). ROC curve indicated that the immune genes risk scores model had a good reliability in predicting prognosis (5-year OS, AUC = 0.752). The established risk model showed splendid AUC value in the validation dataset (3-year over survival (OS) AUC = 0.685, 5-year OS AUC = 0.717, P = 0.00048). Moreover, the immune risk signature was proved to be an independent prognostic factor for BC patients. Finally, it was found that 15 immune genes and risk scores had significant clinical correlations, and were involved in a variety of carcinogenic pathways. Conclusion In conclusion, our study provides a new perspective for the expression of immune genes in BC. The constructed model has potential value for the prognostic prediction of BC patients and may provide some references for the clinical precision immunotherapy of patients.


Author(s):  
Wei Jiang ◽  
Jiameng Xu ◽  
Zirui Liao ◽  
Guangbin Li ◽  
Chengpeng Zhang ◽  
...  

ObjectiveTo screen lung adenocarcinoma (LUAC)-specific cell-cycle-related genes (CCRGs) and develop a prognostic signature for patients with LUAC.MethodsThe GSE68465, GSE42127, and GSE30219 data sets were downloaded from the GEO database. Single-sample gene set enrichment analysis was used to calculate the cell cycle enrichment of each sample in GSE68465 to identify CCRGs in LUAC. The differential CCRGs compared with LUAC data from The Cancer Genome Atlas were determined. The genetic data from GSE68465 were divided into an internal training group and a test group at a ratio of 1:1, and GSE42127 and GSE30219 were defined as external test groups. In addition, we combined LASSO (least absolute shrinkage and selection operator) and Cox regression analysis with the clinical information of the internal training group to construct a CCRG risk scoring model. Samples were divided into high- and low-risk groups according to the resulting risk values, and internal and external test sets were used to prove the validity of the signature. A nomogram evaluation model was used to predict prognosis. The CPTAC and HPA databases were chosen to verify the protein expression of CCRGs.ResultsWe identified 10 LUAC-specific CCRGs (PKMYT1, ETF1, ECT2, BUB1B, RECQL4, TFRC, COCH, TUBB2B, PITX1, and CDC6) and constructed a model using the internal training group. Based on this model, LUAC patients were divided into high- and low-risk groups for further validation. Time-dependent receiver operating characteristic and Cox regression analyses suggested that the signature could precisely predict the prognosis of LUAC patients. Results obtained with CPTAC, HPA, and IHC supported significant dysregulation of these CCRGs in LUAC tissues.ConclusionThis prognostic prediction signature based on CCRGs could help to evaluate the prognosis of LUAC patients. The 10 LUAC-specific CCRGs could be used as prognostic markers of LUAC.


2021 ◽  
Vol 12 ◽  
Author(s):  
Guomin Wu ◽  
Qihao Wang ◽  
Ting Zhu ◽  
Linhai Fu ◽  
Zhupeng Li ◽  
...  

This study aimed to establish a prognostic risk model for lung adenocarcinoma (LUAD). We firstly divided 535 LUAD samples in TCGA-LUAD into high-, medium-, and low-immune infiltration groups by consensus clustering analysis according to immunological competence assessment by single-sample gene set enrichment analysis (ssGSEA). Profile of long non-coding RNAs (lncRNAs) in normal samples and LUAD samples in TCGA was used for a differential expression analysis in the high- and low-immune infiltration groups. A total of 1,570 immune-related differential lncRNAs in LUAD were obtained by intersecting the above results. Afterward, univariate COX regression analysis and multivariate stepwise COX regression analysis were conducted to screen prognosis-related lncRNAs, and an eight-immune-related-lncRNA prognostic signature was finally acquired (AL365181.2, AC012213.4, DRAIC, MRGPRG-AS1, AP002478.1, AC092168.2, FAM30A, and LINC02412). Kaplan–Meier analysis and ROC analysis indicated that the eight-lncRNA-based model was accurate to predict the prognosis of LUAD patients. Simultaneously, univariate COX regression analysis and multivariate COX regression analysis were undertaken on clinical features and risk scores. It was illustrated that the risk score was a prognostic factor independent from clinical features. Moreover, immune data of LUAD in the TIMER database were analyzed. The eight-immune-related-lncRNA prognostic signature was related to the infiltration of B cells, CD4+ T cells, and dendritic cells. GSEA enrichment analysis revealed significant differences in high- and low-risk groups in pathways like pentose phosphate pathway, ubiquitin mediated proteolysis, and P53 signaling pathway. This study helps to treat LUAD patients and explore molecules related to LUAD immune infiltration to deeply understand the specific mechanism.


2021 ◽  
Vol 16 ◽  
Author(s):  
Dongqing Su ◽  
Qianzi Lu ◽  
Yi Pan ◽  
Yao Yu ◽  
Shiyuan Wang ◽  
...  

Background: Breast cancer has plagued women for many years and caused many deaths around the world. Method: In this study, based on the weighted correlation network analysis, univariate Cox regression analysis and least absolute shrinkage and selection operator, 12 immune-related genes were selected to construct the risk score for breast cancer patients. The multivariable Cox regression analysis, gene set enrichment analysis and nomogram were also conducted in this study. Results: Good results were obtained in the survival analysis, enrichment analysis, multivariable Cox regression analysis and immune-related feature analysis. When the risk score model was applied in 22 breast cancer cohorts, the univariate Cox regression analysis demonstrated that the risk score model was significantly associated with overall survival in most of the breast cancer cohorts. Conclusion: Based on these results, we could conclude that the proposed risk score model may be a promising method, and may improve the treatment stratification of breast cancer patients in the future work.


2020 ◽  
Author(s):  
Ruihua Fang ◽  
Lin Chen ◽  
Jing Liao ◽  
Jierong Luo ◽  
Chenchen Zhang ◽  
...  

Abstract Background: Head and neck squamous cell carcinoma (HNSCC), the most frequent subtype of head and neck cancer, continues to have a poor prognosis with no improvement. Growing evidence has demonstrated that the immune system plays a crucial role in the development and progression of HNSCC. The goal of our study was to develop an immune-related signature for accurately predicting the survival of HNSCC patients. Methods: Gene expression profiles were established from a total of 546 HNSCC and normal tissues to establish a training set and 83 HNSCC tissues for a validation set. Differentially expressed prognostic immune genes were identified by univariate Cox regression analysis and a corresponding network of differentially expressed transcription factors (TFs) were identified using Cytoscape. The immune-related gene signature was established and validated by univariate Cox regression analysis, least absolute shrinkage and selector operation (LASSO), and multivariate Cox regression analyses. In addition, the prognostic value of the immune-related signature was analyzed by survival and Cox regression analysis. Finally, the correlation between the immune-related signature and the immune microenvironment was established.Results: In this study, the TF-mediated network revealed that Foxp3 plays a central role in the regulatory mechanism of most immune genes. A prognostic signature based on 10 immune-related genes, which divided patients into high and low risk groups, was developed and successfully validated using two independent databases. Our prognostic signature was significantly related to worse survival and predicted prognosis in patients with different clinicopathological factors. A nomogram including clinical characteristics was also constructed for accurate prediction. Furthermore, it was determined that our prognostic signature may act as an independent factor for predicting the survival of HNSCC patients. ROC analysis also revealed that our signature had superior predictive value compared with TNM stage. As for the immune microenvironment, our signature showed a positive correlation with activated mast cells and M0 macrophages, a negative correlation with Tregs, and immune checkpoint molecules PD-1 and CLTA-4. Conclusions: Our study established an immune-related gene signature, which not only provides a promising biomarker for survival prediction, but may be evaluated as an indicator for personalized immunotherapy in patients with HNSCC.


2021 ◽  
Author(s):  
Weijie Xue ◽  
Bingzi Dong ◽  
Yixiu Wang ◽  
Yuwei Xie ◽  
Qingkai Xue ◽  
...  

Abstract Background Stomach adenocarcinoma (STAD) is one of the most common malignant tumors worldwide. In this study, we attempt to construct a valid immune-associated gene prognostic index risk model which could predict the survival of HCC patients and the efficacy of immune check point inhibitors (ICIs) treatment. Methods The transcriptome, clinical and gene mutational data were obtained from the TCGA database. And immune-related genes were downloaded from the ImmPort and InnateDB databases. Functional and enrichment analysis was performed to identify the potential molecular function and mechanism of these differentially expressed immune-associated genes. And then candidates genes related to overall survival (OS) of STAD was obtained by weighted gene co-expression network analysis (WGCNA). Next, the immune prognostic risk model was constructed via multivariate Cox regression analysis and verified with GEO STAD cohort. Afterwards, the association between the risk model and the immune characteristics and was estimated. Finally, the correlation between the risk model and efficacy of ICIs therapy. Results A total of 493 immune-related genes were identified to enriched in function associated to immune response as well as in immune and tumor-related pathways. Based on the cox regression analysis, we constructed an immune-associated gene prognostic index (IAGPI) risk model based on 8 genes (RNASE2, CGB5, INHBE, PTGER3, CTLA4, DUSP1, APOA1 and CD36). Patients were divided into two subsets according to risk score. Patients in low risk set had a better OS than those in high. In the low risk set, there were more CD8 T cells, activated memory CD4 T cells, follicular helper T cells and M1 macrophages, while monocytes, M2 macrophages, eosinophils and neutrophils were more plentiful in the high. And patients in the low risk set were more sensitive to ICIs therapy. Conclusion The IAGPI risk model can precisely predict prognosis, reflect tumor immune microenvironment and predict the efficacy of ICIs therapy in STAD patients.


2020 ◽  
Author(s):  
Ze-bing Song ◽  
Guo-pei Zhang ◽  
shaoqiang li

Abstract Background: Hepatocellular carcinoma (HCC) is one of the most common malignant tumor in the world which prognosis is poor. Therefore, a precise biomarker is needed to guide treatment and improve prognosis. More and more studies have shown that lncRNAs and immune response are closely related to the prognosis of hepatocellular carcinoma. The aim of this study was to establish a prognostic signature based on immune related lncRNAs for HCC.Methods: Univariate cox regression analysis was performed to identify immune related lncRNAs, which had negative correlation with overall survival (OS) of 370 HCC patients from The Cancer Genome Atlas (TCGA). A prognostic signature based on OS related lncRNAs was identified by using multivariate cox regression analysis. Gene set enrichment analysis (GSEA) and a competing endogenous RNA (ceRNA) network were performed to clarify the potential mechanism of lncRNAs included in prognostic signature. Results: A prognostic signature based on OS related lncRNAs (AC145207.5, AL365203.2, AC009779.2, ZFPM2-AS1, PCAT6, LINC00942) showed moderately in prognosis prediction, and related with pathologic stage (Stage I&II VS Stage III&IV), distant metastasis status (M0 VS M1) and tumor stage (T1-2 VS T3-4). CeRNA network constructed 15 aixs among differentially expressed immune related genes, lncRNAs included in prognostic signature and differentially expressed miRNA. GSEA indicated that these lncRNAs were involved in cancer-related pathways. Conclusion: We constructed a prognostic signature based on immune related lncRNAs which can predict prognosis and guide therapies for HCC.


2020 ◽  
Author(s):  
Deng Rong ◽  
Yu yun ◽  
Lin chen ◽  
Dong Yuxiang ◽  
Pan Yitong ◽  
...  

Abstract Objective: There are increasing evidences that the immune micro-environment of breast cancer (BC) seriously affects the clinical outcome. This study aims to explore the role of tumor immune genes in the prognosis of BC patients.Methods: We obtained the list of 2498 immune genes from ImmPort database. In addition, we obtained gene expression data and clinical characteristics data of BC patients from the TCGA database. The prognostic correlation of the differential genes was analyzed through Survival package. Cox regression analysis was performed to analyze the prognostic effect of immune genes. According to the regression coefficients of prognostic immune genes in regression analysis, an immune risk scores model was established. Gene set enrichment analysis (GSEA) was performed to probe the biological correlation of immune gene scores. P< 0.05 was considered to be statistically significant. Results: In total, 556 immune genes were differentially expressed in normal tissues and BC tissues (p<0. 05). In univariate cox regression analysis, a total of 66 immune genes were statistically significant for survival risk, of which 30 were associated with overall survival (P<0.05). Through lasso regression analysis, a 15 immune genes risk scores model was established. KM survival analysisrevealed that high immune risk scores represented worse survival (p<0.001). ROC curve indicated that the immune genes risk scores model had good a reliability in predicting prognosis (5-year OS, AUC=0.752). The established risk model showed splendid AUC value in the validation dataset (3-year over survival (OS) AUC=0.685, 5-year OS AUC=0.717, P=0.00048). Moreover, immune risk scoreswere proved to be an independent influencing factor for BC patients. Finally, we found that 15 immune genes and risk scores had significant clinical correlations, and were involved in a variety of carcinogenic pathways.Conclusion:In a word, our study provides a new perspective for the expression of immune genes in BC. In addition, the immune risk scores have considerable advantages in predicting the survival of BC, which ares associated with a variety of oncogenic pathways.


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