Oxidative Stress-Related lncRNAs Are Potential Biomarkers for Predicting Prognosis and Immune Responses in Patients With LUAD.
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ABSTRACT:
SUBMITTER: Sun X
PROVIDER: S-EPMC9214656 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Lung adenocarcinoma (LUAD) is the most frequent subtype of lung cancer worldwide. However, the survival rate of LUAD patients remains low. N6-methyladenosine (m6A) and long noncoding RNAs (lncRNAs) play vital roles in the prognostic value and the immunotherapeutic response of LUAD. Thus, discerning lncRNAs associated with m6A in LUAD patients is critical. In this study, m6A-related lncRNAs were analyzed and obtained by coexpression. Univariate, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analyses were conducted to construct an m6A-related lncRNA model. Kaplan-Meier analysis, principal-component analysis (PCA), functional enrichment annotation, and nomogram were used to analyze the risk model. Finally, the potential immunotherapeutic signatures and drug sensitivity prediction targeting this model were also discussed. The risk model comprising 12 m6A-related lncRNAs was identified as an independent predictor of prognoses. By regrouping the patients with this model, we can distinguish between them more effectively in terms of the immunotherapeutic response. Finally, candidate compounds aimed at LUAD subtype differentiation were identified. This risk model based on the m6A-based lncRNAs may be promising for the clinical prediction of prognoses and immunotherapeutic responses in LUAD patients.
| S-EPMC8094594 | biostudies-literature
Project description:The prognosis of the most common histological subtype of lung cancer, lung adenocarcinoma (LUAD), is relatively poor. Mitochondrial homeostasis depends to a great extent on the coordination between mitophagy and mitochondrial biogenesis, the deregulation of which causes various human diseases, including cancer. There is accumulating evidence that long noncoding RNAs (lncRNAs) are critical in predicting the prognosis and immune response in carcinoma. Therefore, it is critical to discern lncRNAs related to mitochondrial homeostasis in LUAD patients. In this study, we identified mitochondrial homeostasis-related lncRNAs (MHRlncRNAs) by coexpression analysis. In order to construct a prognostic signature composed of three MHRlncRNAs, univariate and multivariate Cox regression analyses were performed. Kaplan-Meier analysis, stratification analysis, principal component analysis (PCA), receiver operating characteristic (ROC) curve, gene set enrichment analysis (GSEA), and nomogram were applied to evaluate and optimize the risk model. Subsequently, we identified the mitochondrial homeostasis-related lncRNA signature (MHLncSig) as an independent predictive factor of prognosis. Based on the LUAD subtypes regrouped by this risk model, we further investigated the underlying tumor microenvironment, tumor mutation burden, and immune landscape behind different risk groups. Likewise, individualized immunotherapeutic strategies and candidate compounds were screened to aim at different risk subtypes of LUAD patients. Finally, we validated the expression trends of lncRNAs included in the risk model using quantitative real-time polymerase chain reaction (qRT-PCR) assays. The established MHLncSig may be a promising tool for predicting the prognosis and guiding individualized treatment in LUAD.
| S-EPMC9234294 | biostudies-literature
Project description:Lung adenocarcinoma (LUAD) is a malignant disease with an extremely poor prognosis, and there is currently a lack of clinical methods for early diagnosis and precise treatment and management. With the deepening of tumor research, more and more attention has been paid to the role of immune checkpoints (ICP) and long non-coding RNAs (lncRNAs) regulation in tumor development. Therefore, this study downloaded LUAD patient data from the TCGA database, and finally screened 14 key ICP-related lncRNAs based on ICP-related genes using univariate/multivariate COX regression analysis and LASSO regression analysis to construct a risk prediction model and corresponding nomogram. After multi-dimensional testing of the model, the model showed good prognostic prediction ability. In addition, to further elucidate how ICP plays a role in LUAD, we jointly analyzed the immune microenvironmental changes in LAUD patients and performed a functional enrichment analysis. Furthermore, to enhance the clinical significance of this study, we performed a sensitivity analysis of common antitumor drugs. All the above works aim to point to new directions for the treatment of LUAD.
| S-EPMC9533213 | biostudies-literature
Project description:Uterine corpus endometrial carcinoma (UCEC) is a malignant disease that, at present, has no well-characterised prognostic biomarker. In this study, two clusters were identified based on 28 N1-methyladenosine- (m1A-) related long noncoding RNAs (lncRNAs), of which cluster 1 was related to immune pathways according to the results of an enrichment analysis. We further observed better prognosis in patients with higher levels of immune cell infiltration, tumor mutation burden, microsatellite instability, and immune checkpoint gene expression. In addition, through Cox regression analysis and least absolute shrinkage and selection operator regression analysis, 10 m1A-related lncRNAs (mRLs) were employed to build a prognosis model. We found that people in higher risk categories had a poorer survival probability than those in lower risk. Low-risk samples were enriched with immune-related pathways, while the high-risk group was similar to the definition of the "immune desert" phenotype, which was associated with decreased immune infiltration, T cell failure, and decreased tumor mutation burden, while also being insensitive to immunotherapy and chemotherapy. This mRL-based model has the ability to accurately predict the prognosis of UCEC patients, and the mRLs could become promising therapeutic targets in enhancing the response of immunotherapy.
| S-EPMC9372539 | biostudies-literature
Project description:BackgroundSeveral recent studies have confirmed epigenetic regulation of the immune response. However, the potential role of RNA N6-methyladenosine (m6A) modifications in cervical cancer and tumour microenvironment (TME) cell infiltration remain unclear.ResultsWe evaluated and analysed m6A modification patterns in 307 cervical cancer samples from The Cancer Genome Atlas (TCGA) dataset based on 13 m6A regulators. Pearson correlation analysis was used to identify lncRNAs associated with m6A, followed by univariate Cox regression analysis to screen their prognostic role in cervical cancer patients. We also correlated TME cell infiltration characteristics with modification patterns. We screened six m6A-associated lncRNAs as prognostic lncRNAs and established the prognostic profile of m6A-associated lncRNAs by least absolute shrinkage and choice of operator (LASSO) Cox regression. The corresponding risk scores of the patients were derived based on their prognostic features, and the correlation between this feature model and disease prognosis was analysed. The prognostic model constructed based on the TCGA-CESC (The Cancer Genome Cervical squamous cell carcinoma and endocervical adenocarcinoma) dataset showed strong prognostic power in the stratified analysis and was confirmed as an independent prognostic indicator for predicting the overall survival of patients with CESC. Enrichment analysis showed that biological processes, pathways, and markers associated with malignancy were more common in the high-risk subgroup. Risk scores were strongly correlated with the tumour grade. ECM receptor interactions and pathways in cancer were enriched in Cluster 2, while oxidative phosphorylation and other biological processes were enriched in Cluster 1. The expression of immune checkpoint molecules, including programmed death 1 (PD-1) and programmed death ligand 1 (PD-L1), was significantly increased in the high-risk subgroup, suggesting that this prognostic model could be a predictor of immunotherapy.ConclusionsThis study reveals that m6A modifications play an integral role in the diversity and complexity of TME formation. Assessing the m6A modification patterns of individual tumours will help improve our understanding of TME infiltration characteristics and thus guide immunotherapy more effectively. We also developed an independent prognostic model based on m6A-associated lncRNAs as a predictor of overall survival, which can also be used as a predictor of immunotherapy.
| S-EPMC8767716 | biostudies-literature
Project description:Oxidative stress, as a characteristic of cellular aerobic metabolism, plays a crucial regulatory role in the development and metastasis of gastric cancer (GC). Long noncoding RNAs (lncRNAs) are important regulators in GC development. However, research on the prognostic patterns of oxidative stress-related lncRNAs (OSRLs) and their functions in the immune microenvironment is currently insufficient. We identified the OSRLs signature (DIP2A-IT1, DUXAP8, TP53TG1, SNHG5, AC091057.1, AL355001.1, ARRDC1-AS1, and COLCA1) from 185 oxidative stress-related genes in The Cancer Genome Atlas (TCGA) cohort via random survival forest and Cox analyses, and the results were subsequently validated in the Gene Expression Omnibus (GEO) dataset. The patients were divided into high- and low-risk groups by the risk score of the OSRLs signature. Longer overall survival was detected in the low-risk group than in the high-risk group in both the TCGA cohort (P < 0. 001, HR = 0.43, 95% CI 0.31-0.62) and the GEO cohort (P = 0.014, HR = 0.67, 95% CI 0.48-0.93). Next, multivariate Cox analysis identified that the risk model was an independent prognostic characteristic (HR > 1, P = 0.005), and time-dependent receiver operating characteristic (ROC) curve analysis and nomogram analysis were utilized to evaluate the predictive ability of the risk model. Next, gene set enrichment analysis revealed that the immune-related pathway, Wnt/[Formula: see text]-catenin signature, mammalian target of rapamycin complex 1 signature, and cytokine‒cytokine receptor interaction was enriched. High-risk patients were more responsive to CD200, TNFSF4, TNFSF9, and BTNL2 immune checkpoint blockade. The results of qRT‒PCR further proved the accuracy of our bioinformatic analysis. Overall, our study identified a novel OSRLs signature that can serve as a promising biomarker and prognostic indicator, which provides a personalized predictive approach for patient prognosis evaluation and treatment.
| S-EPMC10232468 | biostudies-literature
Project description:BackgroundSarcomas are a type of highly heterogeneous malignant tumors originating from mesenchymal tissues. Necroptosis is intricately connected to the oncogenesis and progression of tumors. The main goal of this research is to assess the prognostic value of necroptosis-related lncRNAs (NRlncRNAs) in sarcomas and to develop a risk model based on NRlncRNAs to evaluate prognostic and immune status of the sarcomas.MethodsWe screened NRlncRNAs using the gene co-expression network, developed a prognostic risk model of sarcomas, and then verified the model. Following that, various bioinformatics analysis algorithms were employed to analyze the distinct characteristics of patients of the risk model. Furthermore, the function and regulatory mechanism of NRlncRNA SNHG6 in sarcomas were investigated through osteosarcoma cell experiments, such as qRT-PCR, Western blot, CCK-8, clone formation, and transwell assay.ResultsWe successfully developed a NRlncRNAs-related prognostic risk model and screened 5 prognosis-related NRlncRNAs, with SNGH6 being the most significant for prognosis of patients. According to results, the significant differences exist in prognosis, clinical characteristics, and tumor immune status among patients of the risk model. The experiments of osteosarcoma cells demonstrated that NRlncRNA SNHG6 knockdown significantly attenuated the cells' proliferation, migration, and invasion. qRT-PCR and WB results showed that SNHG6 regulated AXL and AKT signaling.ConclusionsWe have developed an innovative investigation on NRlncRNAs, which can serve as a reference for diagnosis, therapy, and prognosis of sarcomas. Additionally, we demonstrated that NRlncRNA SNHG6 regulated AXL and AKT signaling in osteosarcoma cells and the proliferation, migration, and invasion of tumor cells.
| S-EPMC10817413 | biostudies-literature
Project description:BackgroundColon adenocarcinoma (COAD) is the most common subtype of colon cancer. However, the 5-year survival rate of COAD patients remains unsatisfactory. N6-methyladenosine (m6A) and long noncoding RNAs (lncRNAs) play essential roles in the occurrence and development of COAD. Herein, we are committed to establish and validate a prognostic m6A-related lncRNA signature.MethodsWe obtained m6A-related lncRNAs by coexpression. The m6A-related lncRNA risk signature (m6ALncSig) was developed via univariate, LASSO, and multivariate Cox regression analyses. Kaplan-Meier (KM) survival curves, gene set enrichment analysis (GSEA), and nomogram generation were conducted to assess m6ALncSig. In addition, the potential immunotherapeutic signatures were also discussed. Real-time PCR and CCK8 analysis were performed to evaluate the expression and functions of lncRNA UBA6-AS1, which was selected.ResultsThe risk signature comprising 14 m6A-related lncRNAs (m6ALncSig) was established, which possessed a superior predictive ability of prognosis. Meanwhile, m6ALncSig was linked to immune cell infiltration. The level of UBA6-AS1 expression was validated in 17 pairs of COAD samples. In cell function experiments, UBA6-AS1 knockdown attenuated cell proliferation capacity.ConclusionsCollectively, m6ALncSig could serve as an independent predictive factor for COAD and accurately estimate the outcome for COAD patients. Importantly, UBA6-AS1 was first identified as an oncogene in COAD.
| S-EPMC9472555 | biostudies-literature
Project description:Long noncoding RNAs (lncRNAs) are emerging as critical regulators of gene expression and they play fundamental roles in immune regulation. Here we introduce an integrated algorithm, ImmLnc, for identifying lncRNA regulators of immune-related pathways. We comprehensively chart the landscape of lncRNA regulation in the immunome across 33 cancer types and show that cancers with similar tissue origin are likely to share lncRNA immune regulators. Moreover, the immune-related lncRNAs are likely to show expression perturbation in cancer and are significantly correlated with immune cell infiltration. ImmLnc can help prioritize cancer-related lncRNAs and further identify three molecular subtypes (proliferative, intermediate, and immunological) of non-small cell lung cancer. These subtypes are characterized by differences in mutation burden, immune cell infiltration, expression of immunomodulatory genes, response to chemotherapy, and prognosis. In summary, the ImmLnc pipeline and the resulting data serve as a valuable resource for understanding lncRNA function and to advance identification of immunotherapy targets.
| S-EPMC7035327 | biostudies-literature
Project description:BackgroundLong non-coding RNAs (LncRNAs) regulating the immune microenvironment of cancer is a hot spot. But little is known about the influence of the immune-related lncRNA (IRlncRs) on the chemotherapeutic responses and prognosis of cervical cancer (CC) patients. The purpose of the study was to identify an immune-related lncRNAs (IRlncRs)-based model for the prospective prediction of clinical outcomes in CC patients.MethodsCC patients' relevant data was acquired from The Cancer Genome Atlas (TCGA). Correlation analysis and Cox regression analyses were applied. A risk score formula was formulated. Prognostic factors were combined into a nomogram, while sensitivity for chemotherapy drugs was analyzed using the OncoPredict algorithm.ResultsEight optimal IRlncRs(ATP2A1-AS1, LINC01943, AL158166.1, LINC00963, AC009065.8, LIPE-AS1, AC105277.1, AC098613.1.) were incorporated in the IRlncRs model. The overall survival (OS) of the high-risk group of the model was inferior to those in the low-risk group. Further analysis demonstrated this eight-IRlncRs model as a useful prognostic marker. The Nomogram had a concordance index of survival prediction of 0.763(95% CI 0.746-0.780) and more robust predictive accuracy. Furthermore, patients in the low-risk group were found to be more sensitive to chemotherapy, including Paclitaxel, Rapamycin, Epirubicin, Vincristine, Docetaxel and Vinorelbine.ConclusionsAn eight-IRlncRs-based prediction model was identified that has the potential to be an important tool to predict chemotherapeutic responses and prognosis for CC patients.
| S-EPMC11016529 | biostudies-literature