Dataset Information

Identification of platinum resistance-related gene signature for prognosis and immune analysis in bladder cancer.

ABSTRACT: Purpose: Currently, there is limited knowledge about platinum resistance-related long non-coding RNAs (lncRNAs) in bladder cancer. We aim to identify platinum resistance-related lncRNAs and construct a risk model for accurate prognostic prediction of bladder cancer. Methods: Transcriptomic and clinical data were extracted from The Cancer Genome Atlas (TCGA) database, and platinum resistance-related genes were obtained from HGSOC-Platinum. The platinum resistance-related lncRNAs were obtained by the Spearman correlation analysis. Then, we constructed a risk score model through Cox regression analysis and the LASSO algorithm. The model was verified by analyzing the median risk score, Kaplan-Meier curve, receiver operating characteristic (ROC) curve, and heatmap. We also developed a nomogram and examined the relationship between the risk score model, immune landscape, and drug sensitivity. Lastly, we assessed the differential expression of PRR-lncRNAs in the cisplatin-resistant bladder cancer cell line and the normal bladder cancer cell line using qRT-PCR. Results: We developed and validated an eight-platinum resistance-related lncRNA risk model for bladder cancer. The risk model showed independent prognostic significance in univariate and multivariate Cox analyses. Based on multivariate analysis, we developed a nomogram. The modified model is both good predictive and clinically relevant after evaluation. Furthermore, immune-related and drug-sensitivity analyses also showed significant differential expression between high and low-risk groups. The qRT-PCR demonstrated that most of the lncRNAs were upregulated in cisplatin-resistance cancerous tissues than in control tissues. Conclusion: We have developed a predictive model based on eight platinum resistance-related lncRNAs, which could add meaningful information to clinical decision-making.

SUBMITTER: Li S

PROVIDER: S-EPMC9908994 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Identification of platinum resistance-related gene signature for prognosis and immune analysis in bladder cancer.

Li Sheng S Jiang Ming M Yang Lin L Zheng Fucun F Liu Jiahao J Situ Xiong X Liu Xiaoqiang X Weipeng Liu L Fu Bin B

Frontiers in genetics 20230126

<b>Purpose:</b> Currently, there is limited knowledge about platinum resistance-related long non-coding RNAs (lncRNAs) in bladder cancer. We aim to identify platinum resistance-related lncRNAs and construct a risk model for accurate prognostic prediction of bladder cancer. <b>Methods:</b> Transcriptomic and clinical data were extracted from The Cancer Genome Atlas (TCGA) database, and platinum resistance-related genes were obtained from HGSOC-Platinum. The platinum resistance-related lncRNAs wer ...[more]

PMID: 36777726

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Project description:Background Bladder cancer is the tenth most common cancer worldwide. Valuable biomarkers in the field of diagnostic bladder cancer are urgently required. Method Here, the gene expression matrix and clinical data were obtained from The Cancer Genome Atlas (TCGA), GSE13507, GSE32894, and Mariathasan et al. Five prognostic genes were identified by the univariate, robust, and multivariate Cox's regression and were used to develop a prognosis-related model. The Kaplan–Meier survival curves and receiver operating characteristics were used to evaluate the model's effectiveness. The potential biological functions of the selected genes were analyzed using CIBERSORT and ESTIMATE algorithms. Cancer Therapeutics Response Portal (CTRP) and PRISM datasets were used to identify drugs with high sensitivity. Subsequently, using the bladder cancer (BLCA) cell lines, the role of TNFRSF14 was determined by Western blotting, cell proliferation assay, and 5-ethynyl-20-deoxyuridine assay. Results GSDMB, CLEC2D, APOL2, TNFRSF14, and GBP2 were selected as prognostic genes in bladder cancer patients. The model's irreplaceable reliability was validated by the training and validation cohorts. CD8+ T cells were highly infiltrated in the high-TNFRSF14-expression group, and M2 macrophages were the opposite. Higher expression of TNFRSF14 was associated with higher expression levels of LCK, interferon, MHC-I, and MHC-II, while risk score was the opposite. Many compounds with higher sensitivity for treating bladder cancer patients in the low-TNFRSF14-expression group were identified, with obatoclax being a potential drug most likely to treat patients in the low-TNFRSF14-expression group. Finally, the proliferation of BLCA cell lines was increased in the TNFRSF14-reduced group, and the differential expression was identified. TNFRSF14 plays a role in bladder cancer progression through the Wnt/β-catenin-dependent pathway. TNFRSF14 is a potential protective biomarker involved in cell proliferation in BLCA. Conclusion We conducted a study to establish a 5-gene score model, providing reliable prediction for the outcome of bladder cancer patients and therapeutic drugs to individualize therapy. Our findings provide a signature that might help determine the optimal treatment for individual patients with bladder cancer.

Project description:BackgroundAccumulating evidences demonstrated tumor microenvironment (TME) of bladder cancer (BLCA) may play a pivotal role in modulating tumorigenesis, progression, and alteration of biological features. Currently we aimed to establish a prognostic model based on TME-related gene expression for guiding clinical management of BLCA.MethodsWe employed ESTIMATE algorithm to evaluate TME cell infiltration in BLCA. The RNA-Seq data from The Cancer Genome Atlas (TCGA) database was used to screen out differentially expressed genes (DEGs). Underlying relationship between co-expression modules and TME was investigated via Weighted gene co-expression network analysis (WGCNA). COX regression and the least absolute shrinkage and selection operator (LASSO) analysis were applied for screening prognostic hub gene and establishing a risk predictive model. BLCA specimens and adjacent tissues from patients were obtained from patients. Bladder cancer (T24, EJ-m3) and bladder uroepithelial cell line (SVHUC1) were used for genes validation. qRT-PCR was employed to validate genes mRNA level in tissues and cell lines.Results365 BLCA samples and 19 adjacent normal samples were selected for identifying DEGs. 2141 DEGs were identified and used to construct co-expression network. Four modules (magenta, brown, yellow, purple) were regarded as TME regulatory modules through WGCNA and GO analysis. Furthermore, seven hub genes (ACAP1, ADAMTS9, TAP1, IFIT3, FBN1, FSTL1, COL6A2) were screened out to establish a risk predictive model via COX and LASSO regression. Survival analysis and ROC curve analysis indicated our predictive model had good performance on evaluating patients prognosis in different subgroup of BLCA. qRT-PCR result showed upregulation of ACAP1, IFIT3, TAP1 and downregulation of ADAMTS9, COL6A2, FSTL1,FBN1 in BLCA specimens and cell lines.ConclusionsOur study firstly integrated multiple TME-related genes to set up a risk predictive model. This model could accurately predict BLCA progression and prognosis, which offers clinical implication for risk stratification, immunotherapy drug screen and therapeutic decision.

Dataset Information

Identification of platinum resistance-related gene signature for prognosis and immune analysis in bladder cancer.

Publications

Identification of platinum resistance-related gene signature for prognosis and immune analysis in bladder cancer.

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