Dataset Information

A novel five-lncRNA signature panel improves high-risk survival prediction in patients with cholangiocarcinoma.

ABSTRACT: Cholangiocarcinoma (CCA) is a fatal disease with dismal survival rates. Long non-coding RNA (lncRNA) expression profiling as potential prognostic biomarkers play critical roles in tumor initiation, development, and poor prognosis. Identifying specific lncRNA to predict the prognosis of CCA patients in the early stages is very important for improving a patient's survival. In the current study, we aimed to establish a novel risk-stratification lncRNA signature panel in CCA. The initial lncRNA discovery was identified in The Cancer Genome Atlas database (TCGA cohort). The Cox regression analysis was used to establish the lncRNA prognostic model and the receiver operating characteristic (ROC) curve analysis was performed to assess the specificity and sensitivity of the model. This was followed by independent validation of the lncRNA signature in the CCA patients from the First Affiliated Hospital of Wenzhou Medical University (WMU cohort). Furthermore, by using the Gene Ontology function and Kyoto Encyclopedia Gene and Genome pathway enrichment analysis, we explored the potential function of prognosis lncRNA. Finally, five lncRNA (HULC; AL359715.5; AC006504.8; AC090114.2; AP00943.4) were screened to establish the predictive model that significantly associated with poor overall survival(HR:4.879;95%CI,1.587-14.996;p=0.006). This five-lncRNA signature model showed excellent accuracy in the TCGA cohort (AUC=0.938), and also robustly predicted survival in the validation WMU cohort(AUC=0.816). Functional enrichment analysis suggested prognostic lncRNA was primarily associated with CCA-related biological processes. Our data established a novel lncRNA signature model for CCA risk-stratification and robust identification of CCA patients with poor molecular genotypes. Moreover, it revealed new molecular mechanisms of CCA.

SUBMITTER: Xie X

PROVIDER: S-EPMC7880389 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A novel five-lncRNA signature panel improves high-risk survival prediction in patients with cholangiocarcinoma.

Xie Xiaozai X Wang Yi Y Zhang Sina S Li Jialiang J Yu Zhengping Z Ding Xiwei X Ye Longyun L Gong Peirong P Zhu Qiandong Q Li Junjian J Chen Ziyan Z Yao Xinfei X Du Zhiyong Z Zeng Qiqiang Q Chen Hanbin H Yang Zhen Z Chen Gang G

Aging 20210120 2

Cholangiocarcinoma (CCA) is a fatal disease with dismal survival rates. Long non-coding RNA (lncRNA) expression profiling as potential prognostic biomarkers play critical roles in tumor initiation, development, and poor prognosis. Identifying specific lncRNA to predict the prognosis of CCA patients in the early stages is very important for improving a patient's survival. In the current study, we aimed to establish a novel risk-stratification lncRNA signature panel in CCA. The initial lncRNA disc ...[more]

PMID: 33472169

Similar Datasets

Project description:Background: Head and neck squamous cell carcinoma (HNSCC) is a highly prevalent and malignant tumor that is difficult to effectively prognosticate outcomes. Recent reports have suggested that inflammation is strongly related to tumor progression, and several biomarkers linked to inflammation have been demonstrated to be useful for making a prognosis. The goal of this research was to explore the relevance between the inflammatory-related genes and HNSCC prognosis. Methods: The clinical information and gene expression data of patients with HNSCC were acquired from publicly available data sources. A multigene prognostic signature model was constructed in The Cancer Genome Atlas and verified in the Gene Expression Omnibus database. According to the risk score calculated for each patient, they were divided into low- and high-risk groups based on the median. The Kaplan-Meier survival curve and receiver operating characteristic curve were applied to determine the prognostic value of the risk model. Further analysis identified the independent prognostic factors, and a prognostic nomogram was built. The relationship between tumor immune infiltration status and risk scores was investigated using Spearman correlation analysis. Finally, to confirm the expression of genes in HNSCC, quantitative real-time polymerase chain reaction (qRT-PCR) was performed. Results: A prognostic model consisting of 14 inflammatory-related genes was constructed. The samples with a high risk had an apparently shorter overall survival than those with a low risk. Independent prognostic analysis found that risk scores were a separate prognostic factor in HNSCC patients. Immune infiltration analysis suggested that the abundance of B cells, CD8 T cells, M2 macrophages, myeloid dendritic cells, and monocytes in the low-risk group was higher, while that of M0, M1 macrophages, and resting NK cells was obviously higher in the high-risk group. The risk scores were related to chemotherapeutic sensitivity and the expression of several immune checkpoint genes. Moreover, CCL22 and IL10 were significantly higher in HNSCC tissues, as determined by qRT-PCR. Conclusion: Taken together, we constructed a novel inflammatory response-related gene signature, which may be used to estimate outcomes for patients with HNSCC and may be developed into a powerful tool for forecasting the efficacy of immunotherapeutic and chemotherapeutic drugs for HNSCC.

Project description:Aim: Osteosarcoma is the most common primary malignant tumor of bone. However, our understanding of the prognostic indicators and the genetic mechanisms of the disease progression are still incomplete. The aim of this study was to identify a long noncoding RNA (lncRNA) risk signature for osteosarcoma survival prediction. Methods: RNA sequencing data and relevant clinical information of osteosarcoma patients were downloaded from the database of Therapeutically Applicable Research to Generate Effective Treatments (TARGET). We analyzed the differentially expressed lncRNAs between deceased and living patients by univariate and multivariate Cox regression analysis to identify a risk signature. We calculated a prognostic risk score for each sample according to this prognosis signature, and divided patients into high-risk and low-risk groups according to the median value of the risk score (0.975). Kaplan-Meier analysis and receiver operating characteristic (ROC) curve statistics were used to evaluate the performance of the signature. Next, we analyzed the signature's potential function through Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene-set enrichment analysis (GSEA). Lastly, qRT-PCR was used to validate the expression levels of the four lncRNAs in clinical samples. Results: Twenty-six differentially expressed lncRNAs were identified between deceased and living patients. Four of these lncRNAs (CTB-4E7.1, RP11-553A10.1, RP11-24N18.1, and PVRL3-AS1) were identified as independent prognostic factors, and a risk signature of these four lncRNAs for osteosarcoma survival prediction was constructed. Kaplan-Meier analysis showed that the five-year survival time in high-risk and low-risk groups was 33.1% and 82.5%, and the area under the curve (AUC) of the ROC was 0.784, which demonstrated that the prognostic signature was reliable and had the potential to predict the survival of patients with osteosarcoma. The expression level of the four lncRNAs in osteosarcoma tissues and cells was determined by qRT-PCR. Functional enrichment analysis suggested that the signature might be related to osteosarcoma through regulation of the MAPK signaling pathway, the PI3K-Akt signaling pathway, and the extracellular matrix and also provided new insights into the study of osteosarcoma, including the role of papillomavirus infection, olfactory receptor activity, and olfactory transduction in osteosarcoma. Conclusion: We constructed a novel lncRNA risk signature that served as an independent biomarker for predicting the prognosis of osteosarcoma patients.

Project description:BackgroundEndometrial cancer (UCEC) is a complex malignant tumor characterized by both genetic level and clinical trial. Patients with UCEC exhibit the similar clinical features, however, they have distinct outcomes due to molecular heterogeneity. The aim of this study was to access the prognostic value of long non-coding RNAs (lncRNAs) in UCEC patients and to identify potential lncRNA signature for predicting patients' survival and improving patient-tailored treatment.MethodsWe performed a comprehensive genome-wide analysis of lncRNA expression profiles and clinical data in a large cohort of 301 UCEC patients. UCEC patients were randomly divided into the discovery cohort (n = 150) and validation cohort (n = 151). A novel lncRNA-focus expression signature was identified in the discovery cohort, and independently accessed in the validation cohort. Additionally, the lncRNA signature was evaluated by multivariable Cox regression and stratification analysis as well as functional enrichment analysis.ResultsWe detected a novel lncRNA-focus expression signature (LFES) consisting of 11 lncRNAs that were associated with survival based on risk scoring strategy in UCEC. The risk score based on the LFES was able to separate patients of discovery cohort into high-risk and low-risk groups with significantly different overall survival and progression-free survival, and has been successfully confirmed in the validation cohort. Furthermore, the LFES is an independent prognostic predictor of survival and demonstrates superior prognostic performance compared with the clinical covariates for predicting 5-year survival (AUC = 0.887). Functional analysis has linked the expression of prognostic lncRNAs to well-known tumor suppressor or ontogenetic pathways in endometrial carcinogenesis.ConclusionsOur study revealed a novel 11-lncRNA signature to predict survival of UCEC patient. This lncRNA signature may be a valuable and alternative marker for risk evaluation to aid patient-tailored treatment and improve the outcome of patients with UCEC.

Project description:Aims. This study is aimed at identifying a prognostic signature for cervical cancer. Main Methods. The gene expression data and clinical information of cervical cancer and normal cervical tissues were acquired from The Cancer Genome Atlas and from three datasets of the Gene Expression Omnibus database. DESeq2 and Limma were employed to screen differentially expressed genes (DEGs). The overlapping DEGs among all datasets were considered the final DEGs. Then, the functional enrichment analysis was performed. Moreover, the Cox proportional hazards regression was performed to establish a prognostic signature of the DEGs. The Kaplan-Meier analysis was applied to test the model. Relationships between gene expression and clinicopathological parameters in cervical cancer, including age, HPV status, histology, stage, and lymph node metastasis, were analysed by the chi-square test. The somatic mutations of these prognostic genes were assessed through cBioPortal. The robustness of the model was verified in another two independent validation cohorts. Key Findings. In total, 169 overlapping upregulated genes and 29 overlapping downregulated genes were identified in cervical cancer compared with normal cervical tissues. Functional enrichment analysis indicated that the DEGs were mainly enriched in DNA replication, the cell cycle, and the p53 signalling pathway. Finally, a 5-gene- (ITM2A, DSG2, SPP1, EFNA1, and MMP1) based prognostic signature was built. According to this model, each patient was given a prognostic-related risk value. The Kaplan-Meier analysis showed that a higher risk was related to worse overall survival in cervical cancer, with an area under the receiver operating characteristic curve of 0.811 for 15 years. The validity of this model in the prediction of cervical cancer outcome was verified in another two independent datasets. In addition, our study also found that the low expression of ITM2A was associated with cervical adenocarcinoma. Interestingly, DSG2 was associated with the HPV status of cervical cancer. Significance. Our study constructed a prognostic model in cervical cancer and discovered two novel genes, ITM2A and DSG2, associated with cervical carcinogenesis and survival.

Dataset Information

A novel five-lncRNA signature panel improves high-risk survival prediction in patients with cholangiocarcinoma.

Publications

A novel five-lncRNA signature panel improves high-risk survival prediction in patients with cholangiocarcinoma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets