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...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-06-01
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| Series: | BMC Cancer |
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| Online Access: | https://doi.org/10.1186/s12885-022-09810-y |
| _version_ | 1811328689009328128 |
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| author | Jian-Di Li Abdirahman Ahmed Farah Zhi-Guang Huang Gao-Qiang Zhai Rui-Gong Wang Jia-Lin Liu Qin-Jie Wang Guan-Lan Zhang Zi-Long Lei Yi-Wu Dang Sheng-Hua Li |
| author_facet | Jian-Di Li Abdirahman Ahmed Farah Zhi-Guang Huang Gao-Qiang Zhai Rui-Gong Wang Jia-Lin Liu Qin-Jie Wang Guan-Lan Zhang Zi-Long Lei Yi-Wu Dang Sheng-Hua Li |
| author_sort | Jian-Di Li |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T15:30:32Z |
| format | Article |
| id | doaj.art-fa51095c77a94371bf8f4372240b4bfd |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-04-13T15:30:32Z |
| publishDate | 2022-06-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-fa51095c77a94371bf8f4372240b4bfd2022-12-22T02:41:24ZengBMCBMC Cancer1471-24072022-06-0122111810.1186/s12885-022-09810-yClinical significance and potential regulatory mechanism of overexpression of pituitary tumor-transforming gene transcription factor in bladder cancerJian-Di Li0Abdirahman Ahmed Farah1Zhi-Guang Huang2Gao-Qiang Zhai3Rui-Gong Wang4Jia-Lin Liu5Qin-Jie Wang6Guan-Lan Zhang7Zi-Long Lei8Yi-Wu Dang9Sheng-Hua Li10Department of Pathology, The First Affiliated Hospital of Guangxi Medical UniversityDepartment of Pathology, The First Affiliated Hospital of Guangxi Medical UniversityDepartment of Pathology, The First Affiliated Hospital of Guangxi Medical UniversityDepartment of Urology, The First Affiliated Hospital of Guangxi Medical UniversityDepartment of Urology, The First Affiliated Hospital of Guangxi Medical UniversityDepartment of Urology, The First Affiliated Hospital of Guangxi Medical UniversityDepartment of Pathology, The First Affiliated Hospital of Guangxi Medical UniversityDepartment of Pathology, The First Affiliated Hospital of Guangxi Medical UniversityDepartment of Pathology, The First Affiliated Hospital of Guangxi Medical UniversityDepartment of Pathology, The First Affiliated Hospital of Guangxi Medical UniversityDepartment of Urology, The First Affiliated Hospital of Guangxi Medical UniversityAbstract 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.https://doi.org/10.1186/s12885-022-09810-yBLCAPTTG1Tumor microenvironmentTranscriptional regulation |
| spellingShingle | Jian-Di Li Abdirahman Ahmed Farah Zhi-Guang Huang Gao-Qiang Zhai Rui-Gong Wang Jia-Lin Liu Qin-Jie Wang Guan-Lan Zhang Zi-Long Lei Yi-Wu Dang Sheng-Hua Li Clinical significance and potential regulatory mechanism of overexpression of pituitary tumor-transforming gene transcription factor in bladder cancer BMC Cancer BLCA PTTG1 Tumor microenvironment Transcriptional regulation |
| title | Clinical significance and potential regulatory mechanism of overexpression of pituitary tumor-transforming gene transcription factor in bladder cancer |
| title_full | Clinical significance and potential regulatory mechanism of overexpression of pituitary tumor-transforming gene transcription factor in bladder cancer |
| title_fullStr | Clinical significance and potential regulatory mechanism of overexpression of pituitary tumor-transforming gene transcription factor in bladder cancer |
| title_full_unstemmed | Clinical significance and potential regulatory mechanism of overexpression of pituitary tumor-transforming gene transcription factor in bladder cancer |
| title_short | Clinical significance and potential regulatory mechanism of overexpression of pituitary tumor-transforming gene transcription factor in bladder cancer |
| title_sort | clinical significance and potential regulatory mechanism of overexpression of pituitary tumor transforming gene transcription factor in bladder cancer |
| topic | BLCA PTTG1 Tumor microenvironment Transcriptional regulation |
| url | https://doi.org/10.1186/s12885-022-09810-y |
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