Dataset Information

Identification and validation of tumor-infiltrating lymphocyte-related prognosis signature for predicting prognosis and immunotherapeutic response in bladder cancer.

ABSTRACT:

Background

It has been discovered that tumor-infiltrating lymphocytes (TILs) are essential for the emergence of bladder cancer (BCa). This study aimed to research TIL-related genes (TILRGs) and create a gene model to predict BCa patients' overall survival.

Methods

The RNA sequencing and clinical data were downloaded from the TGCA and GEO databases. Using Pearson correlation analysis, TILRGs were evaluated. Moreover, hub TILRGs were chosen using a comprehensive analysis. By dividing the TCGA-BCa patients into different clusters based on hub TILRGs, we were able to explore the immune landscape between different clusters.

Results

Here, we constructed a model with five hub TILRGs and split all of the patients into two groups, each of which had a different prognosis and clinical characteristics, TME, immune cell infiltration, drug sensitivity, and immunotherapy responses. Better clinical results and greater immunotherapy sensitivity were seen in the low-risk group. Based on five hub TILRGs, unsupervised clustering analysis identify two molecular subtypes in BCa. The prognosis, clinical outcomes, and immune landscape differed in different subtypes.

Conclusions

The study identifies a new prediction signature based on genes connected to tumor-infiltrating lymphocytes, providing BCa patients with a new theoretical target.

SUBMITTER: Li C

PROVIDER: S-EPMC10041757 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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Publications

Identification and validation of tumor-infiltrating lymphocyte-related prognosis signature for predicting prognosis and immunotherapeutic response in bladder cancer.

Li Canxuan C Xie Weibin W

BMC bioinformatics 20230327 1

<h4>Background</h4>It has been discovered that tumor-infiltrating lymphocytes (TILs) are essential for the emergence of bladder cancer (BCa). This study aimed to research TIL-related genes (TILRGs) and create a gene model to predict BCa patients' overall survival.<h4>Methods</h4>The RNA sequencing and clinical data were downloaded from the TGCA and GEO databases. Using Pearson correlation analysis, TILRGs were evaluated. Moreover, hub TILRGs were chosen using a comprehensive analysis. By dividin ...[more]

PMID: 36973645

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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.

Project description:BackgroundDuring tumor growth, tumor cells interact with their tumor microenvironment (TME) resulting in the development of heterogeneous tumors that promote tumor occurrence and progression. Recently, there has been extensive attention on TME as a possible therapeutic target for cancers. However, an accurate TME-related prediction model is urgently needed to aid in the assessment of patients' prognoses and therapeutic value, and to assist in clinical decision-making. As such, this study aimed to develop and validate a new prognostic model based on TME-associated genes for BC patients.MethodsTranscriptome data and clinical information for BC patients were extracted from The Cancer Genome Atlas (TCGA) database. Gene Expression Omnibus (GEO) and IMvigor210 databases, along with the MSigDB, were utilized to identify genes associated with TMEs (TMRGs). A consensus clustering approach was used to identify molecular clusters associated with TMEs. LASSO Cox regression analysis was conducted to establish a prognostic TMRG-related signature, with verifications being successfully conducted internally and externally. Gene ontology (GO), KEGG, and single-sample gene set enrichment analyses (ssGSEA) were performed to investigate the underlying mechanisms. The potential response to ICB therapy was estimated using the Tumor Immune Dysfunction and Exclusion (TIDE) algorithm and Immunophenoscore (IPS). Additionally, it was found that the expression level of certain genes in the model was significantly correlated with objective responses to anti-PD-1 or anti-PD-L1 treatment in the IMvigor210, GSE111636, GSE176307, or Truce01 (registration number NCT04730219) cohorts. Finally, real-time PCR validation was performed on 10 paired tissue samples, and in vitro cytological experiments were also conducted on BC cell lines.ResultsIn BC patients, 133 genes differentially expressed that were associated with prognosis in TME. Consensus clustering analysis revealed three distinct clinicopathological characteristics and survival outcomes. A novel prognostic model based on nine TMRGs (including C3orf62, DPYSL2, GZMA, SERPINB3, RHCG, PTPRR, STMN3, TMPRSS4, COMP) was identified, and a TMEscore for OS prediction was constructed, with its reliable predictive performance in BC patients being validated. MultiCox analysis showed that the risk score was an independent prognostic factor. A nomogram was developed to facilitate the clinical viability of TMEscore. Based on GO and KEGG enrichment analyses, biological processes related to ECM and collagen binding were significantly enriched among high-risk individuals. In addition, the low-risk group, characterized by a higher number of infiltrating CD8+ T cells and a lower burden of tumor mutations, demonstrated a longer survival time. Our study also found that TMEscore correlated with drug susceptibility, immune cell infiltration, and the prediction of immunotherapy efficacy. Lastly, we identified SERPINB3 as significantly promoting BC cells migration and invasion through differential expression validation and in vitro phenotypic experiments.ConclusionOur study developed a prognostic model based on nine TMRGs that accurately and stably predicted survival, guiding individual treatment for patients with BC, and providing new therapeutic strategies for the disease.

Dataset Information

Identification and validation of tumor-infiltrating lymphocyte-related prognosis signature for predicting prognosis and immunotherapeutic response in bladder cancer.

Background

Methods

Results

Conclusions

Publications

Identification and validation of tumor-infiltrating lymphocyte-related prognosis signature for predicting prognosis and immunotherapeutic response in bladder cancer.

Similar Datasets

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