Dataset Information

Characterization of hazard infiltrating immune cells and relative risk genes in bladder urothelial carcinoma.

ABSTRACT:

Objectives

Bladder urothelial carcinoma (BLCA) is one of the most common malignancies in urinary system. With the development of next-generation sequencing technology, we intended to investigate prognostic immune cells and related signature to predict the prognosis of BLCA and potential therapeutic targets.

Methods

We obtained the transcriptome profiles of 573 BLCA patients from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The fractions of immune cells in each sample was calculated by "CIBERSORT" algorithm. Tumor Infiltrating Immune Cells Scores (TIICS) was accordingly derived and Receiver Operating Characteristic (ROC) curve was conducted to evaluate the predictive efficiency. Moreover, differential analysis was performed between two TIICS groups and hub TIICS-related immune signature was identified. The correlation of key immune genes and immune-infiltrating immune cells was evaluated based on the TIMER database. An Immune Signature Prognostic Index (ISPI) based on these signatures was constructed with superior predictive accuracy. Last, the TIICS model or related immune signature were all validated in an independent cohort from the GSE13507.

Results

The least absolute shrinkage and selection operator (LASSO) algorithm was utilized to screen the 6 hub tumor-infiltrating immune cells in TCGA cohort, where higher infiltrating levels of M0 Macrophages, M2 Macrophages and Neutrophils were hazard factors, while CD8⁺ T cells and memory activated CD4⁺ T cells were protective factors.

Conclusion

Taken together, our study identified several prognostic immune cells and related immune signature in BLCA, shedding insight on the individualized immunotherapy or potential drug targets.

SUBMITTER: Lv Y

PROVIDER: S-EPMC7724318 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Characterization of hazard infiltrating immune cells and relative risk genes in bladder urothelial carcinoma.

Lv Yinxiang Y Jin Peng P Chen Zheng Z Zhang Peng P

American journal of translational research 20201115 11

<h4>Objectives</h4>Bladder urothelial carcinoma (BLCA) is one of the most common malignancies in urinary system. With the development of next-generation sequencing technology, we intended to investigate prognostic immune cells and related signature to predict the prognosis of BLCA and potential therapeutic targets.<h4>Methods</h4>We obtained the transcriptome profiles of 573 BLCA patients from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The fractions of immune cel ...[more]

PMID: 33312386

Similar Datasets

Project description:BackgroundUrothelial carcinoma of the bladder (UCB) is the most prevalent malignant tumor of the urinary system worldwide, which has a significant recurrence rate despite multiple treatment options available. As a unique and novel copper-dependent programmed cell death mechanism, the comprehensive impact of cuproptosis on the tumor immune microenvironment, clinicopathological characteristics and the prognosis of patients remains largely unclear.MethodsA total of 568 UCB samples were thoroughly examined for cuproptosis patterns using data downloaded from TCGA and GEO, based on 10 cuproptosis-related genes reported previously. Then, the univariate COX regression analysis was performed on the genes that differed across the various patterns. To measure individual cuproptosis pattern, a cuproptosis score system was constructed using a principal component analysis algorithm. To validate the scoring system, immunohistochemical staining was performed on tumor tissues with different pathological grades, and experiments in vitro were conducted about the differentially expressed genes related to prognosis. Finally, the capacity of scoring system to predict the response to immunotherapy was verified by using data from IMvigor 210 cohort.ResultsFour unique cuproptosis clusters and two gene clusters were finally found by the investigation. The clinical features and prognosis of patients, as well as the mRNA transcriptome, pathway enrichment, and immune cell infiltration in TME, varied dramatically between various cuproptosis clusters and gene clusters. To identify individual cuproptosis patterns in UCB patients, we also established a cuproptosis scoring system. After validation with multiple methods, it was indicated that the score system could predict the prognosis of UCB patients and was significantly connected to clinical features such TNM category, tumor grade, molecular type and ultimate survival status. The clinical outcomes of UCB patients were predicted effectively according to the tumor mutation burden in conjunction with the scoring system. Furthermore, we found that the cuproptosis score had a significant correlation with the response to immunotherapy and the sensitivity to chemotherapy.ConclusionThis study revealed the potential impact of cuproptosis on the UCB tumor immune microenvironment and clinical pathological characteristics. The cuproptosis score system could effectively predict the prognosis of patients and the response to chemotherapy and immunotherapy.

Project description:BackgroundDifferent genomic characterization in urothelial carcinoma (UC) by site of origin may imply contrasting therapeutic opportunities and pathogenetic mechanisms. The aim of this study was to investigate whether differences between upper tract UC (UTUC) and UC of the bladder (UCB) result from intrinsic biological diversity.Materials and methodsWe prospectively sequenced 118 tumors and matched blood DNA from Chinese patients with UC using next-generation sequencing techniques, including 45 UTUC and 73 UCB. Two hundred twenty-six patients with UTUC and 350 patients with UCB for The Cancer Genome Atlas were acquired from the cbioportal.ResultsThere were marked disparities in the mutational landscape for UC according to race and site of origin. Signature 22 for exposure to aristolochic acid was only observed in the UTUC cohort. Conversely, signature 6 for defective DNA mismatch repair only existed in the UCB cohort. Compared with UCB, UTUC had higher clonal and subclonal mutation numbers. TP53, PIK3CA, and FGFR3 mutations may be the driver genes for UTUC, whereas for UCB, the driver gene may be BRCA1. Patients with UTUC had lower PD-L1 than those with UCB. There was no significant difference in the number of DDR mutations, copy number variation counts, and tumor mutational burden between UTUC and UCB.ConclusionUTUC and UCB exhibit significant differences in the prevalence of genomic landscape and carcinogenesis. Consequently, molecular subtypes differ according to location, and these results may imply the site-specific management of patients with urothelial carcinoma. Mutational signature may be used as a screening tool to assist clinical differential diagnosis between UTUC and UCB.Implications for practiceThis study's findings lay the foundation for a deeper understanding of distinct molecular mechanisms and similar treatment opportunities between upper tract urothelial carcinoma (UTUC) and urothelial carcinoma of the bladder (UCB) and had important implications for the site-specific management of patients with urothelial carcinoma. A comprehensive understanding of the biology of UTUC and UCB is needed to identify new drug targets in order to improve clinical outcomes.

Dataset Information

Characterization of hazard infiltrating immune cells and relative risk genes in bladder urothelial carcinoma.

Objectives

Methods

Results

Conclusion

Publications

Characterization of hazard infiltrating immune cells and relative risk genes in bladder urothelial carcinoma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets