scholarly journals A prognostic model based on immune-related long noncoding RNAs for patients with epithelial ovarian cancer

2022 ◽  
Vol 15 (1) ◽  
Author(s):  
Yao Peng ◽  
Hui Wang ◽  
Qi Huang ◽  
Jingjing Wu ◽  
Mingjun Zhang

Abstract Background Long noncoding RNAs (lncRNAs) are important regulators of gene expression and can affect a variety of physiological processes. Recent studies have shown that immune-related lncRNAs play an important role in the tumour immune microenvironment and may have potential application value in the treatment and prognosis prediction of tumour patients. Epithelial ovarian cancer (EOC) is characterized by a high incidence and poor prognosis. However, there are few studies on immune-related lncRNAs in EOC. In this study, we focused on immune-related lncRNAs associated with survival in EOC. Methods We downloaded mRNA data for EOC patients from The Cancer Genome Atlas (TCGA) database and mRNA data for normal ovarian tissue from the Genotype-Tissue Expression (GTEx) database and identified differentially expressed genes through differential expression analysis. Immune-related lncRNAs were obtained through intersection and coexpression analysis of differential genes and immune-related genes from the Immunology Database and Analysis Portal (ImmPort). Samples in the TCGA EOC cohort were randomly divided into a training set, validation set and combination set. In the training set, Cox regression analysis and LASSO regression were performed to construct an immune-related lncRNA signature. Kaplan–Meier survival analysis, time-dependent ROC curve analysis, Cox regression analysis and principal component analysis were performed for verification in the training set, validation set and combination set. Further studies of pathways and immune cell infiltration were conducted through Gene Set Enrichment Analysis (GSEA) and the Timer data portal. Results An immune-related lncRNA signature was identified in EOC, which was composed of six immune-related lncRNAs (KRT7-AS, USP30-AS1, AC011445.1, AP005205.2, DNM3OS and AC027348.1). The signature was used to divide patients into high-risk and low-risk groups. The overall survival of the high-risk group was lower than that of the low-risk group and was verified to be robust in both the validation set and the combination set. The signature was confirmed to be an independent prognostic biomarker. Principal component analysis showed the different distribution patterns of high-risk and low-risk groups. This signature may be related to immune cell infiltration (mainly macrophages) and differential expression of immune checkpoint-related molecules (PD-1, PDL1, etc.). Conclusions We identified and established a prognostic signature of immune-related lncRNAs in EOC, which will be of great value in predicting the prognosis of clinical patients and may provide a new perspective for immunological research and individualized treatment in EOC.

2021 ◽  
Author(s):  
Yao Peng ◽  
Hui Wang ◽  
Qi Huang ◽  
Jingjing Wu ◽  
Mingjun Zhang

Abstract Background: Long non-coding RNA (lncRNA), as an important regulator of gene expression, can affect a variety of physiological processes. Recent studies have shown that immune-related lncRNA play an important role in the tumor immune microenvironment and may have potential application value in the treatment and prognosis prediction of tumor patients. Epithelial ovarian cancer (EOC) is characterized by high incidence and poor prognosis. However, there are few studies on immune-related lncRNAs in EOC. In this study, we focused on the immune-related lncRNAs associated with survival in EOC. Methods: We downloaded mRNA data for EOC patients from The Cancer Genome Atlas (TCGA) database, and mRNA data for normal ovarian tissue from the Genotype-Tissue Expression (GTEx) database, and identified differential genes through differential Expression analysis. Immune-related lncRNAs were obtained through taking intersection and co-expression analysis of differential genes and immune-related genes from the Immunology Database and Analysis Portal (ImmPort). Samples in the TCGA EOC cohort were randomly divided into training set, validation set and combination set. In the training set, Cox regression analysis and LASSO regression were used to construct an immune-related lncRNA signature. Kaplan-Meier survival analysis, time-dependent ROC curve analysis, Cox regression analysis and principal component analysis were applied to verification in the training set, training set, validation set and combination set. Further studies of pathways and immune cell infiltration were conducted through Gene Set Enrichment Analysis (GESA) and the Timer data portal.Results: An immune-related lncRNA signature was identified in EOC, which was composed of six immune-related lncRNAs (KRT7-AS, USP30-AS1, AC011445.1, AP005205.2, DNM3OS and AC027348.1). The signature divided patients into high-risk and low-risk groups. The overall survival of the high-risk group was lower than that of the low-risk group, and was verified to be robust in both the training set and the combination set. This signature was identified as an independent prognostic biomarker. The signature was confirmed to be an independent prognostic biomarker. Principal component analysis showed the different distribution patterns of high-risk and low-risk groups. This signature may be related to immune cell infiltration (mainly macrophages) and differential expression of immune checkpoint-related molecules (PD-1, PDL1, etc.). Conclusions: we identified and established a prognostic signature of immune-related lncRNA in EOC, which is of great value in predicting the prognosis of clinical patients and may provide a new perspective for the immunological research and individualized treatment in EOC.


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.


2020 ◽  
Author(s):  
Li Liu ◽  
She Tian ◽  
Zhu Li ◽  
Yongjun Gong ◽  
Hao Zhang

Abstract Background : Hepatocellular carcinoma (HCC) is one of the most common clinical malignant tumors, resulting in high mortality and poor prognosis. Studies have found that LncRNA plays an important role in the onset, metastasis and recurrence of hepatocellular carcinoma. The immune system plays a vital role in the development, progression, metastasis and recurrence of cancer. Therefore, immune-related lncRNA can be used as a novel biomarker to predict the prognosis of hepatocellular carcinoma. Methods : The transcriptome data and clinical data of HCC patients were obtained by using The Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA‑LIHC), and immune-related genes were extracted from the Molecular Signatures Database (IMMUNE RESPONSE M19817 and IMMUNE SYSTEM PROCESS M13664). By constructing the co-expression network and Cox regression analysis, 13 immune-lncRNAs was identified to predict the prognosis of HCC patients. Patients were divided into high risk group and low risk group by using the risk score formula, and the difference in overall survival (OS) between the two groups was reflected by Kaplan-Meier survival curve. The time - dependent receiver operating characteristics (ROC) analysis and principal component analysis (PCA) were used to evaluate 13 immune -lncRNAs signature. Results : Through TCGA - LIHC extracted from 343 cases of patients with hepatocellular carcinoma RNA - Seq data and clinical data, 331 immune-related genes were extracted from the Molecular Signatures Database , co-expression networks and Cox regression analysis were constructed, 13 immune-lncRNAs signature was identified as biomarkers to predict the prognosis of patients. At the same time using the risk score median divided the patients into high risk and low risk groups, and through the Kaplan-Meier survival curve analysis found that high-risk group of patients' overall survival (OS) less low risk group of patients. The AUC value of the ROC curve is 0.828, and principal component analysis (PCA) results showed that patients could be clearly divided into two parts by immune-lncRNAs, which provided evidence for the use of 13 immune-lncRNAs signature as prognostic markers. Conclusion : Our study identified 13 immune-lncRNAs signature that can effectively predict the prognosis of HCC patients, which may be a new prognostic indicator for predicting clinical outcomes.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Fei Li ◽  
Dongcen Ge ◽  
Shu-lan Sun

Abstract Background Ferroptosis is a newly discovered form of cell death characterized by iron-dependent lipid peroxidation. This study aims to investigate the potential correlation between ferroptosis and the prognosis of lung adenocarcinoma (LUAD). Methods RNA-seq data were collected from the LUAD dataset of The Cancer Genome Atlas (TCGA) database. Based on ferroptosis-related genes, differentially expressed genes (DEGs) between LUAD and paracancerous specimens were identified. The univariate Cox regression analysis was performed to screen key genes associated with the prognosis of LUAD. LUAD patients were divided into the training set and validation set. Then, we screened out key genes and built a prognostic prediction model involving 5 genes using the least absolute shrinkage and selection operator (LASSO) regression with tenfold cross-validation and the multivariate Cox regression analysis. After dividing LUAD patients based on the median level of risk score as cut-off value, the generated prognostic prediction model was validated in the validation set. Moreover, we analyzed the somatic mutations, and estimated the scores of immune infiltration in the high-risk and low-risk groups. Functional enrichment analysis of DEGs was performed as well. Results High-risk scores indicated the worse prognosis of LUAD. The maximum area under curve (AUC) of the training set and the validation set in this study was 0.7 and 0.69, respectively. Moreover, we integrated the age, gender, and tumor stage to construct the composite nomogram. The charts indicated that the AUC of LUAD cases with the survival time of 1, 3 and 5 years was 0.698, 0.71 and 0.73, respectively. In addition, the mutation frequency of LUAD patients in the high-risk group was significantly higher than that in the low-risk group. Simultaneously, DEGs were mainly enriched in ferroptosis-related pathways by analyzing the functional results. Conclusions This study constructs a novel LUAD prognosis prediction model involving 5 ferroptosis-related genes, which can be used as a promising tool for decision-making of clinical therapeutic strategies of LUAD.


2021 ◽  
Author(s):  
Fei Li ◽  
Dongcen Ge ◽  
Shu-lan Sun

Abstract Background. Ferroptosis is a newly discovered form of cell death characterized by iron-dependent lipid peroxidation. The aim of this study is to investigate the relationship between ferroptosis and the prognosis of lung adenocarcinoma (LUAD).Methods. RNA-seq data was collected from the LUAD dataset of The Cancer Genome Altas (TCGA) database. We used ferroptosis-related genes as the basis, and identify the differential expression genes (DEGs) between cancer and paracancer. The univariate Cox regression analysis were used to screen the prognostic-related genes. We divided the patients into training and validation sets. Then, we screened out key genes and built a 5 genes prognostic prediction model by the applications of the least absolute shrinkage and selection operator (LASSO) 10-fold cross-validation and the multi-variate Cox regression analysis. We divided the cases by the median value of risk score and validated this model in the validation set. Meanwhile, we analyzed the somatic mutations, and estimated the score of immune infiltration in the high- and low-risk groups, as well as performed functional enrichment analysis of DEGs.Results. The result revealed that the high-risk score triggered the worse prognosis. The maximum area under curve (AUC) of the training set and the validation set of in this study was 0.7 and 0.69. Moreover, we integrated the age, gender, and tumor stage to construct the composite nomogram. The charts indicated that the AUC of cases with survival time of 1, 3 and 5 years are 0.698, 0.71 and 0.73. In addition, the mutation frequency of patients in the high-risk group was higher than that in the low-risk group. Simultaneously, DEGs were mainly enriched in ferroptosis-related pathways by analyzing the functional results.Conclusion. This study constructed a novel LUAD prognosis prediction model base on 5 ferroptosis-related genes, which can provide a prognostic evaluation tool for the clinical therapeutic decision.


2021 ◽  
Vol 18 (5) ◽  
pp. 6709-6723
Author(s):  
Xin Yu ◽  
◽  
Jun Liu ◽  
Ruiwen Xie ◽  
Mengling Chang ◽  
...  

<abstract> <sec><title>Objective</title><p>We aimed to construct a novel prognostic model based on N6-methyladenosine (m6A)-related autophagy genes for predicting the prognosis of lung squamous cell carcinoma (LUSC).</p> </sec> <sec><title>Methods</title><p>Gene expression profiles and clinical information of Patients with LUSC were downloaded from The Cancer Genome Atlas (TCGA) database. In addition, m6A- and autophagy-related gene profiles were obtained from TCGA and Human Autophagy Database, respectively. Pearson correlation analysis was performed to identify the m6A-related autophagy genes, and univariate Cox regression analysis was conducted to screen for genes associated with prognosis. Based on these genes, LASSO Cox regression analysis was used to construct a prognostic model. The corresponding prognostic score (PS) was calculated, and patients with LUSC were assigned to low- and high-risk groups according to the median PS value. An independent dataset (GSE37745) was used to validate the prognostic ability of the model. CIBERSORT was used to calculate the differences in immune cell infiltration between the high- and low-risk groups.</p> </sec> <sec><title>Results</title><p>Seven m6A-related autophagy genes were screened to construct a prognostic model: <italic>CASP4</italic>, <italic>CDKN1A</italic>, <italic>DLC1</italic>, <italic>ITGB1</italic>, <italic>PINK1</italic>, <italic>TP63</italic>, and <italic>EIF4EBP1</italic>. In the training and validation sets, patients in the high-risk group had worse survival times than those in the low-risk group; the areas under the receiver operating characteristic curves were 0.958 and 0.759, respectively. There were differences in m6A levels and immune cell infiltration between the high- and low-risk groups.</p> </sec> <sec><title>Conclusions</title><p>Our prognostic model of the seven m6A-related autophagy genes had significant predictive value for LUSC; thus, these genes may serve as autophagy-related therapeutic targets in clinical practice.</p> </sec> </abstract>


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.


PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11074
Author(s):  
Jin Duan ◽  
Youming Lei ◽  
Guoli Lv ◽  
Yinqiang Liu ◽  
Wei Zhao ◽  
...  

Background Lung adenocarcinoma (LUAD) is the most commonhistological lung cancer subtype, with an overall five-year survivalrate of only 17%. In this study, we aimed to identify autophagy-related genes (ARGs) and develop an LUAD prognostic signature. Methods In this study, we obtained ARGs from three databases and downloaded gene expression profiles from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. We used TCGA-LUAD (n = 490) for a training and testing dataset, and GSE50081 (n = 127) as the external validation dataset.The least absolute shrinkage and selection operator (LASSO) Cox and multivariate Cox regression models were used to generate an autophagy-related signature. We performed gene set enrichment analysis (GSEA) and immune cell analysis between the high- and low-risk groups. A nomogram was built to guide the individual treatment for LUAD patients. Results We identified a total of 83 differentially expressed ARGs (DEARGs) from the TCGA-LUAD dataset, including 33 upregulated DEARGs and 50 downregulated DEARGs, both with thresholds of adjusted P < 0.05 and |Fold change| > 1.5. Using LASSO and multivariate Cox regression analyses, we identified 10 ARGs that we used to build a prognostic signature with areas under the curve (AUCs) of 0.705, 0.715, and 0.778 at 1, 3, and 5 years, respectively. Using the risk score formula, the LUAD patients were divided into low- or high-risk groups. Our GSEA results suggested that the low-risk group were enriched in metabolism and immune-related pathways, while the high-risk group was involved in tumorigenesis and tumor progression pathways. Immune cell analysis revealed that, when compared to the high-risk group, the low-risk group had a lower cell fraction of M0- and M1- macrophages, and higher CD4 and PD-L1 expression levels. Conclusion Our identified robust signature may provide novel insight into underlying autophagy mechanisms as well as therapeutic strategies for LUAD treatment.


PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e8497 ◽  
Author(s):  
Sizhe Wan ◽  
Yuan Nie ◽  
Xuan Zhu

Background The number of elderly hepatocellular carcinoma (HCC) patients is increasing, and precisely assessing of the prognosis of these patients is necessary. We developed a prognostic scoring model to predict survival in elderly HCC patients. Methods We extracted data from 4,076 patients ≥65 years old from the Surveillance, Epidemiology, and End Results (SEER) database and randomly divided them into training and validation groups. Cox regression analysis was used to screen for meaningful independent prognostic factors. The receiver operating characteristic curve reflected the model’s discrimination power. Results Age, race, American Joint Committee on Cancer stage, degree of tumour differentiation, tumour size, alpha-fetoprotein and tumour therapy were independent prognostic factors for survival in elderly HCC patients. We developed a prognostic scoring model based on the seven meaningful variables to predict survival in elderly HCC patients. The AUCs of the model were 0.805 (95% CI [0.788–0.821]) and 0.788 (95% CI [0.759–0.816]) in the training and validation groups, respectively. We divided the patients into low-risk groups and high-risk groups according to the optimal cut-off value. The Kaplan–Meier survival curve showed that in the training and validation groups, the survival rate of the low-risk group was significantly higher than that of the high-risk group (P < 0.001). Conclusion Based on a large population, we constructed a prognostic scoring model for predicting survival in elderly HCC patients. The model may provide a reference for clinicians for preoperative and postoperative evaluations of elderly HCC patients.


2020 ◽  
Author(s):  
Mo Chen ◽  
Tian-en Li ◽  
Pei-zhun Du ◽  
Junjie Pan ◽  
Zheng Wang ◽  
...  

Abstract Background and aims: In this research, we aimed to construct a risk classification model to predict overall survival (OS) and locoregional surgery benefit in colorectal cancer (CRC) patients with distant metastasis.Methods: We selected a cohort consisting of 12741 CRC patients diagnosed with distant metastasis between 2010 and 2014, from the Surveillance, Epidemiology and End Results (SEER) database. Patients were randomly assigned into training group and validation group at the ratio of 2:1. Univariable and multivariable Cox regression models were applied to screen independent prognostic factors. A nomogram was constructed and assessed by the Harrell’s concordance index (C-index) and calibration plots. A novel risk classification model was further established based on the nomogram.Results: Ultimately 12 independent risk factors including race, age, marriage, tumor site, tumor size, grade, T stage, N stage, bone metastasis, brain metastasis, lung metastasis and liver metastasis were identified and adopted in the nomogram. The C-indexes of training and validation groups were 0.77 (95% confidence interval [CI] 0.73-0.81) and 0.75 (95% CI 0.72-0.78), respectively. The risk classification model stratified patients into three risk groups (low-, intermediate- and high-risk) with divergent median OS (low-risk: 36.0 months, 95% CI 34.1-37.9; intermediate-risk: 18.0 months, 95% CI 17.4-18.6; high-risk: 6.0 months, 95% CI 5.3-6.7). Locoregional therapies including surgery and radiotherapy could prognostically benefit patients in the low-risk group (surgery: hazard ratio [HR] 0.59, 95% CI 0.50-0.71; radiotherapy: HR 0.84, 95% CI 0.72-0.98) and intermediate risk group (surgery: HR 0.61, 95% CI 0.54-0.68; radiotherapy: HR 0.86, 95% CI 0.77-0.95), but not in the high-risk group (surgery: HR 1.03, 95% CI 0.82-1.29; radiotherapy: HR 1.03, 95% CI 0.81-1.31). And all risk groups could benefit from systemic therapy (low-risk: HR 0.68, 95% CI 0.58-0.80; intermediate-risk: HR 0.50, 95% CI 0.47-0.54; high-risk: HR 0.46, 95% CI 0.40-0.53).Conclusion: A novel risk classification model predicting prognosis and locoregional surgery benefit of CRC patients with distant metastasis was established and validated. This predictive model could be further utilized by physicians and be of great significance for medical practice.


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