TMEM158 expression is negatively regulated by AR signaling and associated with favorite survival outcomes in prostate cancers
BackgroundMembrane protein TMEM158 was initially reported as a Ras-induced gene during senescence and has been implicated as either an oncogenic factor or tumor suppressor, depending on tumor types. It is unknown if TMEM158 expression is altered in prostate cancers.MethodsMultiple public gene expres...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-11-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.1023455/full |
| _version_ | 1828730964941996032 |
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| author | Jian Huang Wang Liu Da Zhang Biyun Lin Benyi Li Benyi Li |
| author_facet | Jian Huang Wang Liu Da Zhang Biyun Lin Benyi Li Benyi Li |
| author_sort | Jian Huang |
| collection | DOAJ |
| description | BackgroundMembrane protein TMEM158 was initially reported as a Ras-induced gene during senescence and has been implicated as either an oncogenic factor or tumor suppressor, depending on tumor types. It is unknown if TMEM158 expression is altered in prostate cancers.MethodsMultiple public gene expression datasets from RNA-seq and cDNA microarray assays were utilized to analyze candidate gene expression profiles. TMEM158 protein expression was assessed using an immunohistochemistry approach on a tissue section array from benign and malignant prostate tissues. Comparisons of gene expression profiles were conducted using the bioinformatics software R package.ResultsCOX regression-based screening identified the membrane protein TMEM158 gene as negatively associated with disease-specific and progression-free survival in prostate cancer patients. Gene expression at the mRNA and protein levels revealed that TMEM158 expression was significantly reduced in malignant tissues compared to benign compartments. Meanwhile, TMEM158 downregulation was strongly correlated with advanced clinicopathological features, including late-stage diseases, lymph node invasion, higher PSA levels, residual tumors after surgery, and adverse Gleason scores. In castration-resistant prostate cancers, TMEM158 expression was negatively correlated with AR signaling activity but positively correlated with neuroendocrinal progression index. Consistently, in cell culture models, androgen treatment reduced TMEM158 expression, while androgen deprivation led to upregulation of TMEM158 expression. Correlation analysis showed a tight correlation of TMEM158 expression with the level of R-Ras gene expression, which was also significantly downregulated in prostate cancers. Tumor immune infiltration profiling analysis discovered a strong association of TMEM158 expression with NK cell and Mast cell enrichment.ConclusionThe membrane protein TMEM158 is significantly downregulated in prostate cancer and is tightly associated with disease progression, anti-tumor immune infiltration, and patient survival outcome. |
| first_indexed | 2024-04-12T17:37:47Z |
| format | Article |
| id | doaj.art-a4506ca1207f48b39bb3234afac7837b |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-12T17:37:47Z |
| publishDate | 2022-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-a4506ca1207f48b39bb3234afac7837b2022-12-22T03:22:54ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-11-011210.3389/fonc.2022.10234551023455TMEM158 expression is negatively regulated by AR signaling and associated with favorite survival outcomes in prostate cancersJian Huang0Wang Liu1Da Zhang2Biyun Lin3Benyi Li4Benyi Li5Center for Pathological Diagnosis and Research, The Affiliated Hospital of Guangdong Medical University, Zhanjiang, ChinaDepartment of Urology, The University of Kansas Medical Center, Kansas City, KS, United StatesDepartment of Pathology and Laboratory Medicine, The University of Kansas Medical Center, Kansas City, KS, United StatesCenter for Pathological Diagnosis and Research, The Affiliated Hospital of Guangdong Medical University, Zhanjiang, ChinaDepartment of Urology, The University of Kansas Medical Center, Kansas City, KS, United StatesDepartment of Pathology and Laboratory Medicine, The University of Kansas Medical Center, Kansas City, KS, United StatesBackgroundMembrane protein TMEM158 was initially reported as a Ras-induced gene during senescence and has been implicated as either an oncogenic factor or tumor suppressor, depending on tumor types. It is unknown if TMEM158 expression is altered in prostate cancers.MethodsMultiple public gene expression datasets from RNA-seq and cDNA microarray assays were utilized to analyze candidate gene expression profiles. TMEM158 protein expression was assessed using an immunohistochemistry approach on a tissue section array from benign and malignant prostate tissues. Comparisons of gene expression profiles were conducted using the bioinformatics software R package.ResultsCOX regression-based screening identified the membrane protein TMEM158 gene as negatively associated with disease-specific and progression-free survival in prostate cancer patients. Gene expression at the mRNA and protein levels revealed that TMEM158 expression was significantly reduced in malignant tissues compared to benign compartments. Meanwhile, TMEM158 downregulation was strongly correlated with advanced clinicopathological features, including late-stage diseases, lymph node invasion, higher PSA levels, residual tumors after surgery, and adverse Gleason scores. In castration-resistant prostate cancers, TMEM158 expression was negatively correlated with AR signaling activity but positively correlated with neuroendocrinal progression index. Consistently, in cell culture models, androgen treatment reduced TMEM158 expression, while androgen deprivation led to upregulation of TMEM158 expression. Correlation analysis showed a tight correlation of TMEM158 expression with the level of R-Ras gene expression, which was also significantly downregulated in prostate cancers. Tumor immune infiltration profiling analysis discovered a strong association of TMEM158 expression with NK cell and Mast cell enrichment.ConclusionThe membrane protein TMEM158 is significantly downregulated in prostate cancer and is tightly associated with disease progression, anti-tumor immune infiltration, and patient survival outcome.https://www.frontiersin.org/articles/10.3389/fonc.2022.1023455/fullTMEM158prostate cancerpatient survivaldisease progressionAR signalingimmune filtration |
| spellingShingle | Jian Huang Wang Liu Da Zhang Biyun Lin Benyi Li Benyi Li TMEM158 expression is negatively regulated by AR signaling and associated with favorite survival outcomes in prostate cancers Frontiers in Oncology TMEM158 prostate cancer patient survival disease progression AR signaling immune filtration |
| title | TMEM158 expression is negatively regulated by AR signaling and associated with favorite survival outcomes in prostate cancers |
| title_full | TMEM158 expression is negatively regulated by AR signaling and associated with favorite survival outcomes in prostate cancers |
| title_fullStr | TMEM158 expression is negatively regulated by AR signaling and associated with favorite survival outcomes in prostate cancers |
| title_full_unstemmed | TMEM158 expression is negatively regulated by AR signaling and associated with favorite survival outcomes in prostate cancers |
| title_short | TMEM158 expression is negatively regulated by AR signaling and associated with favorite survival outcomes in prostate cancers |
| title_sort | tmem158 expression is negatively regulated by ar signaling and associated with favorite survival outcomes in prostate cancers |
| topic | TMEM158 prostate cancer patient survival disease progression AR signaling immune filtration |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.1023455/full |
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