Dataset Information

Clinical significance and potential regulatory mechanism of overexpression of pituitary tumor-transforming gene transcription factor in bladder cancer.

ABSTRACT:

Background

Pituitary tumor transforming gene-1 (PTTG1) transcription factor is identified as carcinogenic and associated with tumor invasiveness, but its role in bladder cancer (BLCA) remains obscure. This research is intended to analyze the aberrant expression and clinical significance of PTTG1 in BLCA, explore the relationship between PTTG1 and tumor microenvironment characteristics and predict its potential transcriptional activity in BLCA tissue.

Methods

We compared the expression discrepancy of PTTG1 mRNA in BLCA and normal bladder tissue, using the BLCA transcriptomic datasets from GEO, ArrayExpress, TCGA, and GTEx. In-house immunohistochemical staining was implemented to determine the PTTG1 protein intensity. The prognostic value of PTTG1 was evaluated using the Kaplan-Meier Plotter. CRISPR screen data was utilized to estimate the effect PTTG1 interference has on BLCA cell lines. We predicted the abundance of the immune cells in the BLCA tumor microenvironment using the microenvironment cell populations-counter and ESTIMATE algorithms. Single-cell RNA sequencing data was applied to identify the major cell types in BLCA, and the dynamics of BLCA progression were revealed using pseudotime analysis. PTTG1 target genes were predicted by CistromeDB.

Results

The elevated expression level of PTTG1 was confirmed in 1037 BLCA samples compared with 127 non-BLCA samples, with a standardized mean difference value of 1.04. Higher PTTG1 expression status exhibited a poorer BLCA prognosis. Moreover, the PTTG1 Chronos genetic effect scores were negative, indicating that PTTG1 silence may inhibit the proliferation and survival of BLCA cells. With PTTG1 mRNA expression level increasing, higher natural killer, cytotoxic lymphocyte, and monocyte lineage cell infiltration levels were observed. A total of four candidate targets containing CHEK2, OCIAD2, UBE2L3, and ZNF367 were determined ultimately.

Conclusions

PTTG1 mRNA over-expression may become a potential biomarker for BLCA prognosis. Additionally, PTTG1 may correlate with the BLCA tumor microenvironment and exert transcriptional activity by targeting CHEK2, OCIAD2, UBE2L3, and ZNF367 in BLCA tissue.

SUBMITTER: Li JD

PROVIDER: S-EPMC9241226 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BACKGROUND:Regulatory T lymphocytes (Treg) are characterized by the presence of CD4+ surface antigen. Today the transcription factor FOXP3 is considered to be the most specific marker of Treg cells. The aim of the study was to estimate the percentage of Treg in peripheral blood and the tissue of the epithelial ovarian tumor and blood serum TGF-beta concentrations and relationships between them. Moreover, the aim of the study was to answer the question whether the percentage of Treg lymphocytes affects the time of survival in patients with ovarian cancer. METHODS:The patients were divided into four groups, depending on the histopathological examination result: I--a group without any pathology within the ovaries (C; n?=?20), II--a group with benign tumors (B; n?=?25), III - with borderline tumors (BR; n?=?11), IV--a group with cancer of the ovary (M; n?=?24). The percentage of Treg lymphocytes in peripheral blood and the tissue was assessed using the flow cytometry method. TGF-beta cytokine concentration was estimated with the ELISA immunoenzymatic test. Statistical analysis of the results was conducted using the computer program Statistica 10.0PL (StatSoft, Inc). RESULTS:No significant differences were found in percentages of Treg lymphocytes in peripheral blood between individual groups of patients (p?=?0.11). However, we observed marked differences in the tissue of malignant and non-malignant tumors between individual groups of patients (p?=?0.003). The analysis with the post hoc test revealed significantly higher TGF-beta concentration in the group of women with malignant tumors. Moreover, no relationship was found between TGF-beta concentration and the percentage of Treg cells in peripheral blood and tumors of the ovary. No correlation was found between the percentage of Treg lymphocytes in peripheral blood (p?=?0.4) and the tissue of ovarian tumors (p?=?0.3) and the time of survival of patients with ovarian cancer. CONCLUSIONS:The recruitment of Treg lymphocytes toward the tumor is one of the mechanisms of escape of neoplasm from the response of the immune system. The percentage of Treg lymphocytes in peripheral blood and the neoplastic tissue does not influence the time of survival of patients with ovarian cancer.