Clinical significance and potential regulatory mechanism of overexpression of pituitary tumor-transforming gene transcription factor in bladder cancer.
Gene Expression Regulation, Neoplastic
Humans
Kruppel-Like Transcription Factors
/ metabolism
Neoplasm Proteins
/ genetics
Oncogenes
Pituitary Neoplasms
/ genetics
Prognosis
RNA, Messenger
/ genetics
Securin
/ biosynthesis
Transcription Factors
/ genetics
Tumor Microenvironment
/ genetics
Urinary Bladder Neoplasms
BLCA
PTTG1
Transcriptional regulation
Tumor microenvironment
Journal
BMC cancer
ISSN: 1471-2407
Titre abrégé: BMC Cancer
Pays: England
ID NLM: 100967800
Informations de publication
Date de publication:
29 Jun 2022
29 Jun 2022
Historique:
received:
06
04
2022
accepted:
21
06
2022
entrez:
29
6
2022
pubmed:
30
6
2022
medline:
2
7
2022
Statut:
epublish
Résumé
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. 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. 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. 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.
Sections du résumé
BACKGROUND
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
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
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
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.
Identifiants
pubmed: 35768832
doi: 10.1186/s12885-022-09810-y
pii: 10.1186/s12885-022-09810-y
pmc: PMC9241226
doi:
Substances chimiques
Kruppel-Like Transcription Factors
0
Neoplasm Proteins
0
RNA, Messenger
0
Securin
0
Transcription Factors
0
ZNF367 protein, human
0
pituitary tumor-transforming protein 1, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
713Subventions
Organisme : Guangxi Medical University "Future Academic Star" project
ID : WLXSZX21036
Organisme : Guangxi Medical University 2020 Innovation and Entrepreneurship Training Program for College Students
ID : 202110598060
Organisme : Fund of Natural Science Foundation of Guangxi, China
ID : 2018GXNSFAA281175
Organisme : Guangxi Clinical Research Center for Urology and Nephrology
ID : No.2020AC03006
Organisme : Guangxi Science and Technology Base and Talent Project
ID : No.2019AC17009
Informations de copyright
© 2022. The Author(s).
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