TP53-related signature for predicting prognosis and tumor microenvironment characteristics in bladder cancer: a multi-omics study 1 microenvironment characteristic
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PROVIDER: PRJNA891747 | ENA |
REPOSITORIES: ENA
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Project description:Background: The tumor suppressor gene TP53 is frequently mutated or inactivated in bladder cancer (BLCA), which is implicated in the pathogenesis of tumor. However, the cellular mechanisms of TP53 mutations are complicated, yet well-defined, but their clinical prognostic value in the management of BLCA remains controversial. This study aimed to explore the role of TP53 mutation in regulating the tumor microenvironment (TME), elucidate the effects of TP53 activity on BLCA prognosis and immunotherapy response. Methods: A TP53-related signature based on TP53-induced and TP53-repressed genes was used to construct a TP53 activity-related score and classifier. The abundance of different immune cell types was determined using CIBERSORT to estimate immune cell infiltration. Moreover, the heterogeneity of the tumor immune microenvironment between the high and low TP53 score groups was further evaluated using single-cell mass cytometry (CyTOF) and imaging mass cytometry (IMC). Moreover, pathway enrichment analysis was performed to explore the differential biological functions between tumor epithelial cells with high and low TP53 activity scores. Finally, the receptor–ligand interactions between immune cells and tumor epithelial cells harboring distinct TP53 activity were analyzed by single-cell RNA-sequencing. Results: The TP53 activity-related gene signature differentiated well between TP53 functional retention and inactivation in BLCA. BLCA patients with low TP53 scores had worse survival prognosis, more TP53 mutations, higher grade, and stronger lymph node metastasis than those with high TP53 scores. Additionally, CyTOF and IMC analyses revealed that BLCA patients with low TP53 scores exhibited a potent immunosuppressive TME. Consistently, single-cell sequencing results showed that tumor epithelial cells with low TP53 scores were significantly associated with high cell proliferation and stemness abilities and strongly interacted with immunosuppressive receptor–ligand pairs. Conclusions: Patients with BLCA with low TP53 scores have a worse prognosis and a more immunosuppressive TME. This TP53 activity-related signature can serve as a potential prognostic signature for predicting the immune response, which may facilitate the development of new strategies for immunotherapy in BLCA. Keywords: bladder cancer, TP53, immunosuppression, tumor microenvironment
2022-10-24 | GSE216037 | GEO
Project description:Background: The tumor suppressor gene TP53 is frequently mutated or inactivated in bladder cancer (BLCA), which is implicated in the pathogenesis of tumor. However, the cellular mechanisms of TP53 mutations are complicated, yet well-defined, but their clinical prognostic value in the management of BLCA remains controversial. This study aimed to explore the role of TP53 mutation in regulating the tumor microenvironment (TME), elucidate the effects of TP53 activity on BLCA prognosis and immunotherapy response. Methods: A TP53-related signature based on TP53-induced and TP53-repressed genes was used to construct a TP53 activity-related score and classifier. The abundance of different immune cell types was determined using CIBERSORT to estimate immune cell infiltration. Moreover, the heterogeneity of the tumor immune microenvironment between the high and low TP53 score groups was further evaluated using single-cell mass cytometry (CyTOF) and imaging mass cytometry (IMC). Moreover, pathway enrichment analysis was performed to explore the differential biological functions between tumor epithelial cells with high and low TP53 activity scores. Finally, the receptor-ligand interactions between immune cells and tumor epithelial cells harboring distinct TP53 activity were analyzed by single-cell RNA-sequencing. Results: The TP53 activity-related gene signature differentiated well between TP53 functional retention and inactivation in BLCA. BLCA patients with low TP53 scores had worse survival prognosis, more TP53 mutations, higher grade, and stronger lymph node metastasis than those with high TP53 scores. Additionally, CyTOF and IMC analyses revealed that BLCA patients with low TP53 scores exhibited a potent immunosuppressive TME. Consistently, single-cell sequencing results showed that tumor epithelial cells with low TP53 scores were significantly associated with high cell proliferation and stemness abilities and strongly interacted with immunosuppressive receptor-ligand pairs. Conclusion: BLCA patients with low TP53 scores have a worse prognosis and a more immunosuppressive TME. This TP53 activity-related signature can serve as a potential prognostic signature for predicting the immune response, which may facilitate the development of new strategies for immunotherapy in BLCA.
| S-EPMC9780475 | biostudies-literature
Project description:TP53 mutations are a poor prognostic factor in breast cancers. This study sets out to identify the gene set that determine expression signature of the TP53 status (TP53 signature) and to correlate it with clinical outcome. Using comprehensive expression analysis and DNA sequencing of the TP53 gene in 38 Japanese breast cancer patients, we have isolated a gene set of 33 genes from differentially expressed genes in the learning set (n=26), depending on the TP53 status. Predictive accuracy of TP53 status by gene expression profile was 83.3% in the test set (n=12). As independent external datasets, two published datasets were introduced for validation of TP53 status prediction (251 Swedish samples) and survival analysis (both the Swedish and 295 Dutch samples). TP53 signature has the ability to predict recurrence-free survival (RFS) of 29 stage I and II Japanese breast cancers (log rank, P = 0.032), and RFS, overall survival of two independently published datasets (log rank, both P < 0.0001). Multivariate analysis has shown an independent and significant prognostic factor with a hazard ratio (HR) for recurrence and survival in two external datasets (P < 0.0001). The TP53 signature is also a strong prognostic factor in the subgroups: estrogen-receptor positive, lymph node (LN) positive and negative, intermediate/high risk in St. Gallen criteria, and high risk in National Cancer Institute (NCI) criteria (log rank, P < 0.0001). TP53 signature is a reliable and independent predictor of the outcome of disease in operated breast cancer. Keywords: Tumor sample comparison
2006-08-23 | GSE5546 | GEO
Project description:Interventions: Gold Standard:Clinical outcome;Index test:Pathological immunofluorescence analysis was performed to determine the infiltration status of immune cells in postoperative rectal cancer specimens including CD8+, PDL1_1, CD45RO, PD1, CD3, CD8+CD45RO+, CD3+PD1+, CD8+PD1+, FOXP3, CD163, CD68?CD4, PDL1_2, CD68+CD163-, CD68+CD163+, PDL1+CD68+, PDL1+CD68-, CD4+FOXP3+, CD68+CD163+PDL1+, PDL1_A
Primary outcome(s): the area under the receiver operating characteristic (AUC);accuracy;Sensitivity;Specificity;Positive predictive values;Negative predictive values
Study Design: Factorial
| 2696146 | ecrin-mdr-crc
Project description:TP53 mutations are a poor prognostic factor in breast cancers. This study sets out to identify the gene set that determine expression signature of the TP53 status (TP53 signature) and to correlate it with clinical outcome. Using comprehensive expression analysis and DNA sequencing of the TP53 gene in 38 Japanese breast cancer patients, we have isolated a gene set of 33 genes from differentially expressed genes in the learning set (n=26), depending on the TP53 status. Predictive accuracy of TP53 status by gene expression profile was 83.3% in the test set (n=12). As independent external datasets, two published datasets were introduced for validation of TP53 status prediction (251 Swedish samples) and survival analysis (both the Swedish and 295 Dutch samples). TP53 signature has the ability to predict recurrence-free survival (RFS) of 29 stage I and II Japanese breast cancers (log rank, P = 0.032), and RFS, overall survival of two independently published datasets (log rank, both P < 0.0001). Multivariate analysis has shown an independent and significant prognostic factor with a hazard ratio (HR) for recurrence and survival in two external datasets (P < 0.0001). The TP53 signature is also a strong prognostic factor in the subgroups: estrogen-receptor positive, lymph node (LN) positive and negative, intermediate/high risk in St. Gallen criteria, and high risk in National Cancer Institute (NCI) criteria (log rank, P < 0.0001). TP53 signature is a reliable and independent predictor of the outcome of disease in operated breast cancer. Experiment Overall Design: Microarray hybridizations (Agilent: Whole Human Genome Oligo Microarray; 41k unique probe) were carried out with 1μg Cy3 labeled cRNA and 1 μg Cy5 labeled cRNA, both prepared from each sample and reference pool, respectively. Experiment Overall Design: Fluorescent intensities of scanned images were quantified by ArrayVision Ver.8 rev.4 (Imaging research). Experiment Overall Design: The gene expression data was quantified and analyzed by GeneSpring 6.2 (Silicon Genetics). To identify the TP53 status predictor gene set, a Wilcoxon rank sum test along with Benjamini and Hochberg false discovery rate (FDR) was used.
2008-06-13 | E-GEOD-5546 | biostudies-arrayexpress
Project description:LncRNA expression profiles were sucessfully contructed in 370 patients with NSCLC and 198 corresponding adjacent noncancerous tissues using a custom microarray containing probes for 2412 lncRNAs and an outcome prediction of lncRNA signature was successfully identified for predicting prognosis in NSCLC.
2020-08-31 | GSE143018 | GEO
Project description:The adaptor protein LNK (SH2B3) has emerged as an important protein in regulating B cell development B cell leukemia. Loss-of-function mutations in LNK (SH2B3) are found in Philadelphia chromosomeâlike acute lymphoblastic leukemia (Ph-like ALL), but how LNK regulates normal B cell development or promotes leukemogenesis remains unclear. We found that combined loss of Lnk and tumor suppressors Tp53 in mice triggers a highly aggressive and transplantable precursor B-ALL. This study aims to investigate the molecular mechanism by which LNK regulates B-ALL development. We performed expression profiling of bone marrow proB progenitors from WT, Tp53-/-, Lnk-/- and preleukemic healthy Tp53/Lnk double knockout (DKO) mice, as well as leukemic bone marrow cells from DKO mice that have developed B-ALL. Results suggest that Tp53-/-Lnk-/- B-ALLs display similar gene expression profiles to human Ph-like B-ALLs, suggesting this model for preclinical and molecular studies. B220+CD19+CD43+AA4.1+IgM-NK1.1-Ly6c- bone marrow proB cells were double sorted from WT, Tp53-/-, Lnk-/- and preleukemic healthy Tp53/Lnk double knockout (DKO) mice, as well as leukemic bone marrow cells from DKO mice that have developed B-ALL. RNA was isolated using miRNeasy kit from QIAGEN and processed using the NuGEN Pico kit. The microarray analysis was performed at the PENN Molecular Profiling/Genomics Facility using GeneChip Mouse Gene 2.0ST array (Affymetrix).
2016-04-01 | E-GEOD-76940 | biostudies-arrayexpress
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2022-04-27 | PXD029512 | Pride
Project description:Genomic characteristic PDX in cholangiocarcinoma
| PRJEB63092 | ENA