Dataset Information

Characterization of Immune-Related Long Non-coding RNAs to Construct a Novel Signature and Predict the Prognosis and Immune Landscape of Soft Tissue Sarcoma.

ABSTRACT: Background: Increasing evidence has demonstrated that immune-related long non-coding RNAs (irlncRNAs) are critically involved in tumor initiation and progression and associated with the prognosis of various cancers. However, their role in soft tissue sarcoma (STS) remains significantly uninvestigated. Materials and Methods: Gene expression profiles were extracted from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) for the identification of irlncRNAs. Univariate analysis and modified least absolute shrinkage and selection operator (LASSO) penalized regression analysis were employed to determine differently expressed irlncRNA (DEirlncRNA) pairs of prognostic value, and subsequently, a risk signature based on DEirlncRNA pairs was established. Furthermore, Kaplan-Meier analysis and the area under the receiver operating characteristic curve (AUC) were used to assess survival differences and the predictive accuracy of the risk signature, respectively. Lastly, the correlation of irlncRNAs with immune characteristics and chemosensitivity in patients with STS were further investigated. Results: A total of 1088 irlncRNAs were identified, and 311 irlncRNAs were distinguished as DEirlncRNAs. A total of 130 DEirlncRNA pairs were further identified as prognostic markers, and 14 pairs were selected for establishing a risk signature. The irlncRNA-based risk signature functioned as an independent prognostic marker for STS. Compared with the patients in the high-risk group, those in the low-risk group exhibited a better prognosis and were more sensitive to several chemotherapeutic agents. In addition, the irlncRNA-based risk signature was significantly associated with immune scores, infiltrating immune cells, and the expression of several immune checkpoints. Conclusion: In conclusion, our data revealed that the irlncRNA-based risk signature resulted in reliable prognosis, effectively predicted the immune landscape of patients with STS and was significantly correlated with chemosensitivity, thus providing insights into the potential role of irlncRNAs as prognostic biomarkers and novel therapeutic targets for STS.

SUBMITTER: Lin Z

PROVIDER: S-EPMC8497898 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Purpose: This study aimed to construct a novel signature to predict the survival of patients with colon cancer and the associated immune landscape, based on immune-related long noncoding ribonucleic acids (irlncRNAs). Methods: Expression profiles of irlncRNAs in 457 patients with colon cancer were retrieved from the TCGA database (https://portal.gdc.cancer.gov). Differentially expressed (DE) irlncRNAs were identified and irlncRNA pairs were recognized using Lasso regression and Cox regression analyses. Akaike information criterion (AIC) values of receiver operating characteristic (ROC) curve were calculated to identify the ideal cut-off point for dividing patients into two groups and constructing the prognosis signature. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to validate the expression of LINC02195 and SCARNA9 in colon cancer. Results: We identified 22 irlncRNA pairs and patients were divided into high-risk and low-risk groups based on the calculated risk score using these 22 irlncRNA pairs. The irlncRNA pairs were significantly related to patient survival. Low-risk patients had a significantly longer survival time than high-risk patients (p < 0.001). The area under the curve of the signature to predict 5-year survival was 0.951. The risk score correlated with tumor stage, infiltration depth, lymph node metastasis, and distant metastasis. The risk score remained significant after univariate and multivariate Cox regression analyses. A nomogram model to predict patient survival was developed based on the results of Cox regression analysis. Immune cell infiltration status, expression of some immune checkpoint genes, and sensitivity to chemotherapeutics were also related to the risk score. The results of qRT-PCR revealed that LINC02195 and SCARNA9 were significantly upregulated in colon cancer tissues. Conclusion: The constructed prognosis signature showed remarkable efficiency in predicting patient survival, immune cell infiltration status, expression of immune checkpoint genes, and sensitivity to chemotherapeutics.

Project description:Background: With a high incidence and dismal survival rate, hepatocellular carcinoma (HCC) tops the list of the world's most frequent malignant tumors. Immunotherapy is a new approach to cancer treatment, and its effect on prolonging overall survival (OS) varies from patient to patient. For a more effective prognosis and treatment of HCC, we are committed to identifying immune infiltration-related long non-coding RNAs (IIRLs) with prognostic value in hepatocellular carcinoma. Methods: In our study, we calculated immune scores of 369 hepatocellular carcinoma samples from the Cancer Genome Atlas (TCGA) database by using an estimation algorithm, and obtained long non-coding RNAs (lncRNAs) associated with immune infiltration by using Weighted Gene Co-expression Network analysis (WGCNA). For training cohort, univariate Cox, least absolute shrinkage and selection operator (Lasso) and multivariate Cox regression analysis were used to determine prognostic IIRLs, we established a prognostic IIRLs signature. By testing cohort and entire cohort, we confirmed that the signature is practical. The prognosis of people with different clinicopathological stages and risk scores were predicted by the nomogram we constructed. In addition, Immune cell infiltration analysis and prediction of therapeutic drugs were performed. Results: 93 IIRLs were obtained by WGCNA. Furthermore, the prognostic value of these IIRLs were evaluated by using univariate Cox, Lasso and multivariate Cox analysis. Four IIRLs were used to create a signature with a prognosis. Time-related receiver operating characteristic (ROC) curve revealed that this model had an acceptable prognostic value for HCC patients. By using univariate and multivariate Cox regression analysis, this risk score has been shown to be an independent prognostic factor for HCC. The nomogram we made showed good predictions. Except for that, the treatment with immune checkpoint inhibitors (ICI) was likely to be more effective for low-risk patients. Conclusion: Based on four IIRLs, a prognostic signature was created in this research showed good accuracy in predicting OS. This study also provided valuable references for Immunotherapy of hepatocellular carcinoma.

Project description:Background: Cancer-associated fibroblasts (CAFs) are an essential cell population in the pancreatic cancer tumor microenvironment and are extensively involved in drug resistance and immune evasion mechanisms. Long non-coding RNAs (lncRNAs) are involved in pancreatic cancer evolution and regulate the biological behavior mediated by CAFs. However, there is a lack of understanding of the prognostic signatures of CAFs-associated lncRNAs in pancreatic cancer patients. Methods: Transcriptomic and clinical data for pancreatic adenocarcinoma (PAAD) and the corresponding mutation data were obtained from The Cancer Genome Atlas database. lncRNAs associated with CAFs were obtained using co-expression analysis. lncRNAs were screened by Cox regression analysis using least absolute shrinkage and selection operator (LASSO) algorithm for constructing predictive signature. According to the prognostic model, PAAD patients were divided into high-risk and low-risk groups. Kaplan-Meier analysis was used for survival validation of the model in the training and validation groups. Clinicopathological parameter correlation analysis, univariate and multivariate Cox regression, time-dependent receiver operating characteristic (ROC) curves, and nomogram were performed to evaluate the model. The gene set variation analysis (GSVA) and gene ontology (GO) analyses were used to explore differences in the biological behavior of the risk groups. Furthermore, single-sample gene set enrichment analysis (ssGSEA), tumor mutation burden (TMB), ESTIMATE algorithm, and a series of immune correlation analyses were performed to investigate the relationship between predictive signature and the tumor immune microenvironment and screen for potential responders to immune checkpoint inhibitors. Finally, drug sensitivity analyses were used to explore potentially effective drugs in high- and low-risk groups. Results: The signature was constructed with seven CAFs-related lncRNAs (AP005233.2, AC090114.2, DCST1-AS1, AC092171.5, AC002401.4, AC025048.4, and CASC8) that independently predicted the prognosis of PAAD patients. Additionally, the high-risk group of the model had higher TMB levels than the low-risk group. Immune correlation analysis showed that most immune cells, including CD8+ T cells, were negatively correlated with the model risk scores. ssGSEA and ESTIMATE analyses further indicated that the low-risk group had a higher status of immune cell infiltration. Meanwhile, the mRNA of most immune checkpoint genes, including PD1 and CTLA4, were highly expressed in the low-risk group, suggesting that this population may be "hot immune tumors" and have a higher sensitivity to immune checkpoint inhibitors (ICIs). Finally, the predicted half-maximal inhibitory concentrations of some chemical and targeted drugs differ between high- and low-risk groups, providing a basis for treatment selection. Conclusion: Our findings provide promising insights into lncRNAs associated with CAFs in PAAD and provide a personalized tool for predicting patient prognosis and immune microenvironmental landscape.

Project description:BackgroundThyroid cancer (TC) is the most common endocrine malignancy worldwide. The incidence of TC is high and increasing worldwide due to continuous improvements in diagnostic technology. Therefore, identifying accurate prognostic predictions to stratify TC patients is important.MethodsRaw data were downloaded from the TCGA database, and pairwise comparisons were applied to identify differentially expressed immune-related lncRNA (DEirlncRNA) pairs. Then, we used univariate Cox regression analysis and a modified Lasso algorithm on these pairs to construct a risk assessment model for TC. We further used qRT‒PCR analysis to validate the expression levels of irlncRNAs in the model. Next, TC patients were assigned to high- and low-risk groups based on the optimal cutoff score of the model for the 1-year ROC curve. We evaluated the signature in terms of prognostic independence, predictive value, immune cell infiltration, immune status, ICI-related molecules, and small-molecule inhibitor efficacy.ResultsWe identified 14 DEirlncRNA pairs as the novel predictive signature. In addition, the qRT‒PCR results were consistent with the bioinformatics results obtained from the TCGA dataset. The high-risk group had a significantly poorer prognosis than the low-risk group. Cox regression analysis revealed that this immune-related signature could predict prognosis independently and reliably for TC. With the CIBERSORT algorithm, we found an association between the signature and immune cell infiltration. Additionally, immune status was significantly higher in low-risk groups. Several immune checkpoint inhibitor (ICI)-related molecules, such as PD-1 and PD-L1, showed a negative correlation with the high-risk group. We further discovered that our new signature was correlated with the clinical response to small-molecule inhibitors, such as sunitinib.ConclusionsWe have constructed a prognostic immune-related lncRNA signature that can predict TC patient survival without considering the technical bias of different platforms, and this signature also sheds light on TC's overall prognosis and novel clinical treatments, such as ICB therapy and small molecular inhibitors.

Project description:The aim of this study was to construct a new immune-associated long non-coding RNA (lncRNA) signature to predict the prognosis of Ewing sarcoma (ES) and explore its molecular mechanisms. We downloaded transcriptome and clinical prognosis data from the Gene Expression Omnibus (GSE17679, which included 88 ES samples and 18 matched normal skeletal muscle samples), and used it as a training set to identify immune-related lncRNAs with different expression levels in ES. Univariable Cox regression was used to screen immune-related lncRNAs related to ES prognosis, and an immune-related lncRNA signature was constructed based on machine learning iterative lasso regression. An external verification set was used to confirm the predictive ability of the signature. Clinical feature subgroup analysis was used to explore whether the signature was an independent prognostic factor. In addition, CIBERSORT was used to explore immune cell infiltration in the high- and low-risk groups, and to analyze the correlations between the lncRNA signature and immune cell levels. Gene set enrichment and variation analyses were used to explore the possible regulatory mechanisms of the immune-related lncRNAs in ES. We also analyzed the expression of 17 common immunotherapy targets in the high- and low-risk groups to identify any that may be regulated by immune-related lncRNAs. We screened 35 immune-related lncRNAs by univariate Cox regression. Based on this, an immune-related 11-lncRNA signature was generated by machine learning iterative lasso regression. Analysis of the external validation set confirmed its high predictive ability. DPP10 antisense RNA 3 was negatively correlated with resting dendritic cell, neutrophil, and γδ T cell infiltration, and long intergenic non-protein coding RNA 1398 was positively correlated with resting dendritic cells and M2 macrophages. These lncRNAs may affect ES prognosis by regulating GSE17721_CTRL_VS_PAM3CSK4_12H_BMDC_UP, GSE2770_IL4_ACT_VS_ACT_CD4_TCELL_48H_UP, GSE29615_CTRL_VS_DAY3_ LAIV_IFLU_VACCINE_PBMC_UP, complement signaling, interleukin 2-signal transducer and activator of transcription 5 signaling, and protein secretion. The immune-related 11-lncRNA signature may also have regulatory effects on the immunotherapy targets CD40 molecule, CD70 molecule, and CD276 molecule. In conclusion, we constructed a new immune-related 11-lncRNA signature that can stratify the prognoses of patients with ES.

Project description:BackgroundCuproptosis, a recently discovered type of programmed cell death (PCD), paves a new avenue for cancer treatment. It has been revealed that PCD-related lncRNAs play a critical role in various biological processes of lung adenocarcinoma (LUAD). However, the role of cuproptosis-related lncRNA (CuRLs) remains unclear. This study aimed to identify and validate a CuRLs-based signature for the prognostic prediction of patients with LUAD.MethodsRNA sequencing data and clinical information of LUAD were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Pearson correlation analysis was used to identify CuRLs. Univariate Cox regression analysis, Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression, and stepwise multivariate Cox analysis were applied to construct a novel prognostic CuRLs signature. A nomogram was developed for the prediction of patient survival outcomes. Gene set variation analysis (GSVA), gene set enrichment analysis (GSEA), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were utilized to explore potential functions underlying the CuRLs signature. Patients were divided into low- and high-risk groups. Several algorithms, such as tumor immune estimation resource (TIMER), cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT), and QuanTIseq, were combined to comprehensively investigate the differences in immune landscape between different risk groups. Sensitivity to common anticancer drugs was analyzed using the pRRophetic algorithm.ResultsWe constructed a novel prognostic signature based on 10 CuRLs, including CARD8-AS1, RUNDC3A-AS1, TMPO-AS1, MIR31HG, SEPSECS-AS1, DLGAP1-AS1, LINC01137, ZSCAN16-AS1, APTR, and ELOA-AS1. This 10-CuRLs risk signature showed great diagnostic accuracy combined with traditional clinical risk factors, and a nomogram was constructed for potential clinical translation. The tumor immune microenvironment was significantly different between different risk groups. Among drugs commonly used in the treatment of lung cancer, the sensitivity of cisplatin, docetaxel, gemcitabine, gefitinib, and paclitaxel was higher in low-risk patients, and patients in the low-risk group may benefit more from imatinib.ConclusionsThese results revealed the outstanding contribution of the CuRLs signature to the evaluation of prognosis and treatment modalities for patients with LUAD. The differences in characteristics between different risk groups provide an opportunity for better patient stratification and to explore novel drugs in different risk groups.

Dataset Information

Characterization of Immune-Related Long Non-coding RNAs to Construct a Novel Signature and Predict the Prognosis and Immune Landscape of Soft Tissue Sarcoma.

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