Dataset Information

Molecular characterization of breast cancer: a potential novel immune-related lncRNAs signature.

ABSTRACT: BACKGROUND:Accumulating evidence has demonstrated that immune-related lncRNAs (IRLs) are commonly aberrantly expressed in breast cancer (BC). Thus, we aimed to establish an IRL-based tool to improve prognosis prediction in BC patients. METHODS:We obtained IRL expression profiles in large BC cohorts (N?=?911) from The Cancer Genome Atlas (TCGA) database. Then, in light of the correlation between each IRL and recurrence-free survival (RFS), we screened prognostic IRL signatures to construct a novel RFS nomogram via a Cox regression model. Subsequently, the performance of the IRL-based model was evaluated through discrimination, calibration ability, risk stratification ability and decision curve analysis (DCA). RESULTS:A total of 52 IRLs were obtained from TCGA. Based on multivariate Cox regression analyses, four IRLs (A1BG-AS1, AC004477.3, AC004585.1 and AC004854.2) and two risk parameters (tumor subtype and TNM stage) were utilized as independent indicators to develop a novel prognostic model. In terms of predictive accuracy, the IRL-based model was distinctly superior to the TNM staging system (AUC: 0.728 VS 0.673, P?=?0.010). DCA indicated that our nomogram had favorable clinical practicability. In addition, risk stratification analysis showed that the IRL-based tool efficiently divided BC patients into high- and low-risk groups (P?

SUBMITTER: Lai J

PROVIDER: S-EPMC7648293 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Molecular characterization of breast cancer: a potential novel immune-related lncRNAs signature.

Lai Jianguo J Chen Bo B Zhang Guochun G Li Xuerui X Mok Hsiaopei H Liao Ning N

Journal of translational medicine 20201107 1

<h4>Background</h4>Accumulating evidence has demonstrated that immune-related lncRNAs (IRLs) are commonly aberrantly expressed in breast cancer (BC). Thus, we aimed to establish an IRL-based tool to improve prognosis prediction in BC patients.<h4>Methods</h4>We obtained IRL expression profiles in large BC cohorts (N = 911) from The Cancer Genome Atlas (TCGA) database. Then, in light of the correlation between each IRL and recurrence-free survival (RFS), we screened prognostic IRL signatures to c ...[more]

PMID: 33160384

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Project description:BACKGROUND:Breast cancer is a highly heterogeneous disease, this poses challenges for classification and management. Long non-coding RNAs play acrucial role in the breast cancersdevelopment and progression, especially in tumor-related immune processes which have become the most rapidly investigated area. Therefore, we aimed at developing an immune-related lncRNA signature to improve the prognosis prediction of breast cancer. METHODS:We obtained breast cancer patient samples and corresponding clinical data from The Cancer Genome Atlas (TCGA) database. Immune-related lncRNAs were screened by co-expression analysis of immune-related genes which were downloaded from the Immunology Database and Analysis Portal (ImmPort). Clinical patient samples were randomly separated into training and testing sets. In the training set, univariate Cox regression analysis and LASSO regression were utilized to build a prognostic immune-related lncRNA signature. The signature was validated in the training set, testing set, and whole cohorts by the Kaplan-Meier log-rank test, time-dependent ROC curve analysis, principal component analysis, univariate andmultivariate Cox regression analyses. RESULTS:A total of 937 immune- related lncRNAs were identified, 15 candidate immune-related lncRNAs were significantly associated with overall survival (OS). Eight of these lncRNAs (OTUD6B-AS1, AL122010.1, AC136475.2, AL161646.1, AC245297.3, LINC00578, LINC01871, AP000442.2) were selected for establishment of the risk prediction model. The OS of patients in the low-risk group was higher than that of patients in the high-risk group (p?=?1.215e?-?06 in the training set; p?=?0.0069 in the validation set; p?=?1.233e?-?07 in whole cohort). The time-dependent ROC curve analysis revealed that the AUCs for OS in the first, eighth, and tenth year were 0.812, 0.81, and 0.857, respectively, in the training set, 0.615, 0.68, 0.655 in the validation set, and 0.725, 0.742, 0.741 in the total cohort. Multivariate Cox regression analysis indicated the model was a reliable and independent indicator for the prognosis of breast cancer in the training set (HR?=?1.432; 95% CI 1.204-1.702, p?<?0.001), validation set (HR?=?1.162; 95% CI 1.004-1.345, p?=?0.044), and whole set (HR?=?1.240; 95% CI 1.128-1.362, p?<?0.001). GSEA analysis revealed a strong connection between the signature and immune-related biological processes and pathways. CONCLUSIONS:We constructed and verified a robust signature of 8 immune-related lncRNAs for the prediction of breast cancer patient survival.

Project description:Background: Ferroptosis, a regulated cell death which is driven by the iron-dependent peroxidation of lipids, plays an important role in cancer. However, studies about ferroptosis-related Long non-coding RNAs (lncRNAs) in breast cancer (BC) are limited. Besides, the prognostic role of ferroptosis-related lncRNAs and their relationship to immune microenvironment in breast cancer remain unclear. This study aimed to explore the potential prognostic value of ferroptosis-related lncRNAs and their relationship to immune microenvironment in breast cancer. Methods: RNA-sequencing data of female breast cancer patients were downloaded from TCGA database. 937 patients were randomly separated into training or validation cohort in 2:1 ratio. Ferroptosis-related lncRNAs were screened by Pearson correlation analysis with 239 reported ferroptosis-related genes. A ferroptosis-related lncRNAs signature was constructed with univariate and multivariate Cox regression analyses in the training cohort, and its prognostic value was further tested in the validation cohort. Results: An 8-ferroptosis-related-lncRNAs signature was developed by multivariate Cox regression analysis to divide patients into two risk groups. Patients in the high-risk group had worse prognosis than patients in the low-risk group. Multivariate Cox regression analysis showed the risk score was an independent prognostic indicator. Receiver operating characteristic curve (ROC) analysis proved the predictive accuracy of the signature. The area under time-dependent ROC curve (AUC) reached 0.853 at 1 year, 0.802 at 2 years, 0.740 at 5 years in the training cohort and 0.791 at 1 year, 0.778 at 2 years, 0.722 at 5 years in the validation cohort. Further analysis demonstrated that immune-related pathways were significantly enriched in the high-risk group. Analysis of the immune cell infiltration landscape showed that breast cancer in the high-risk group tended be immunologically "cold". Conclusion: We identified a novel ferroptosis-related lncRNA signature which could precisely predict the prognosis of breast cancer patients. Ferroptosis-related lncRNAs may have a potential role in the process of anti-tumor immunity and serve as therapeutic targets for breast cancer.

Project description:Background: Neutrophil extracellular traps (NETs) are closely associated to tumorigenesis and development. However, the relationship between NETs-related long non-coding RNAs (lncRNAs) and the characteristics of breast tumor remains an enigma. This study aimed to explore the clinical prognostic value of NETs-related lncRNAs, their correlation with the tumor microenvironment (TME) and their predictive ability of drug sensitivity in patients with breast cancer (BC). Methods: The expression profiles of RNA-sequencing and relevant clinical data of BC patients were extracted from TCGA database. The co-expression network analysis, univariable, least absolute shrinkage and selection operator (LASSO) and multivariable Cox algorithms were employed to construct the NETs-related lncRNAs signature. A nomogram was established and validated to explore the clinical application. Furthermore, the immune microenvironment and drug sensitivity for BC with different prognostic risks were explored. Finally, the expression pattern of lncRNAs was validated using qRT-PCR in BC tissues and their adjacent non-cancerous tissues. Results: Based on NETs-related lncRNAs, a prognostic risk model consisted of 10 lncRNAs (SFTA1P, ACTA2-AS1, AC004816.2, AC000067.1, LINC01235, LINC01010, AL133467.1, AC092919.1, AL591468.1, and MIR200CHG) was established. The Kaplan-Meier analysis showed that the overall survival (OS) was significantly better in low-risk BC patients than in high-risk BC patients (P training cohort < 0.001, P validation cohort = 0.009). The nomogram also showed good predictive accuracy for OS of BC individuals in both training and validation cohorts. The function enrichment analysis revealed that high-risk group was mainly enriched in immune-related functions and pathways, and the tumor mutation burden in this group was markedly higher than that in the low-risk group (p = 0.022). Moreover, significant differences were observed in immune cells, immune functions and immune checkpoint genes among BC patients at different risks (p < 0.05). The response to chemotherapeutic agents and immunotherapy were also closely related with the expression of NETs-related lncRNAs (p < 0.001). The expression of lncRNAs from experimental validation were generally consistent with the bioinformatics analysis results. Conclusion: Our study provided a novel prognostic model for BC and yielded strong scientific rationale for individualized treatment strategies, elucidating immunotherapy in BC patients.

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Molecular characterization of breast cancer: a potential novel immune-related lncRNAs signature.

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Molecular characterization of breast cancer: a potential novel immune-related lncRNAs signature.

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