The Correlations Between the Intensity of Histopathological Ubiquitin-Specific Protease 11 Staining and Progression of Prostate Cancer

Overview

Journal Pharmaceuticals (Basel)

Publisher MDPI

Specialty Chemistry

Date 2023 Dec 23

PMID 38139829

Authors

Jae Heon Kim

Hee Jo Yang

Kwang Woo Lee

Jae Joon Park

Chang-Ho Lee

Youn Soo Jeon

Jae Ho Kim

Suyeon Park

Su Jung Song

Ji-Hye Lee

Ahrim Moon

Yon Hee Kim

Yun Seob Song

Affiliations

Soon will be listed here.

Abstract

Background: Ubiquitin-specific protease 11 (USP11), one of the principal phosphatase and tensin homolog (PTEN) deubiquitinases, can reserve PTEN polyubiquitination to maintain PTEN protein integrity and inhibit PI3K/AKT pathway activation. The aim of the current study was to investigate the associations between immunohistochemical USP11 staining intensities and prognostic indicators in individuals with prostate cancer.

Methods: Tissue microarrays (TMAs) were performed for human prostate cancer and normal tissue (control) samples. Data on patient's age, Gleason score, plasma prostate-specific antigen (PSA) titer, disease stage, and presence of seminal vesicles, lymph nodes, and surgical margin involvement were collected. A pathologist who was blinded to the clinical outcome data scored the TMA for USP11 staining intensity as either positive or negative.

Results: Cancerous tissues exhibited lower USP11 staining intensity, whereas the neighboring benign peri-tumoral tissues showed higher USP11 staining intensity. The degree of USP11 staining intensity was lower in patients with a higher PSA titer, higher Gleason score, or more advanced disease stage. Patients who showed positive USP11 staining were more likely to have more optimal clinical and biochemical recurrence-free survival statistics.

Conclusions: USP11 staining intensity in patients with prostate cancer is negatively associated with several prognostic factors such as an elevated PSA titer and a high Gleason score. It also reflects both biochemical and clinical recurrence-free survival in such patients. Thus, USP11 staining is a valuable prognostic factor in patients with prostate cancer.

Citing Articles

USP54 is a potential therapeutic target in castration-resistant prostate cancer.

Zhou C, Zhang X, Ma H, Zhou Y, Meng Y, Chen C BMC Urol. 2024; 24(1):32.

PMID: 38321455 PMC: 10845770. DOI: 10.1186/s12894-024-01418-7.

References

Swanson D, Freund C, Ploder L, McInnes R, Valle D . A ubiquitin C-terminal hydrolase gene on the proximal short arm of the X chromosome: implications for X-linked retinal disorders. Hum Mol Genet. 1996; 5(4):533-8. DOI: 10.1093/hmg/5.4.533. View

Maddika S, Kavela S, Rani N, Palicharla V, Pokorny J, Sarkaria J . WWP2 is an E3 ubiquitin ligase for PTEN. Nat Cell Biol. 2011; 13(6):728-33. PMC: 3926303. DOI: 10.1038/ncb2240. View

Taylor B, Schultz N, Hieronymus H, Gopalan A, Xiao Y, Carver B . Integrative genomic profiling of human prostate cancer. Cancer Cell. 2010; 18(1):11-22. PMC: 3198787. DOI: 10.1016/j.ccr.2010.05.026. View

Liu R, Graham K, Glubrecht D, Germain D, Mackey J, Godbout R . Association of FABP5 expression with poor survival in triple-negative breast cancer: implication for retinoic acid therapy. Am J Pathol. 2011; 178(3):997-1008. PMC: 3070589. DOI: 10.1016/j.ajpath.2010.11.075. View

Yang-Feng T, Li S, Han H, Schwartz P . Frequent loss of heterozygosity on chromosomes Xp and 13q in human ovarian cancer. Int J Cancer. 1992; 52(4):575-80. DOI: 10.1002/ijc.2910520414. View

Wang X, Trotman L, Koppie T, Alimonti A, Chen Z, Gao Z . NEDD4-1 is a proto-oncogenic ubiquitin ligase for PTEN. Cell. 2007; 128(1):129-39. PMC: 1828909. DOI: 10.1016/j.cell.2006.11.039. View

Cerami E, Gao J, Dogrusoz U, Gross B, Sumer S, Aksoy B . The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discov. 2012; 2(5):401-4. PMC: 3956037. DOI: 10.1158/2159-8290.CD-12-0095. View

Hatano K, Nonomura N . Genomic Profiling of Prostate Cancer: An Updated Review. World J Mens Health. 2021; 40(3):368-379. PMC: 9253799. DOI: 10.5534/wjmh.210072. View

Chung J, Morgan T, Hong S . Clinical implications of genomic evaluations for prostate cancer risk stratification, screening, and treatment: a narrative review. Prostate Int. 2020; 8(3):99-106. PMC: 7557186. DOI: 10.1016/j.prnil.2020.09.001. View

10.

Sacco J, Yau T, Darling S, Patel V, Liu H, Urbe S . The deubiquitylase Ataxin-3 restricts PTEN transcription in lung cancer cells. Oncogene. 2013; 33(33):4265-72. PMC: 4351423. DOI: 10.1038/onc.2013.512. View

11.

Song M, Salmena L, Carracedo A, Egia A, Lo-Coco F, Teruya-Feldstein J . The deubiquitinylation and localization of PTEN are regulated by a HAUSP-PML network. Nature. 2008; 455(7214):813-7. PMC: 3398484. DOI: 10.1038/nature07290. View

12.

Sun W, Tan X, Shi Y, Xu G, Mao R, Gu X . USP11 negatively regulates TNFalpha-induced NF-kappaB activation by targeting on IkappaBalpha. Cell Signal. 2009; 22(3):386-94. PMC: 2794974. DOI: 10.1016/j.cellsig.2009.10.008. View

13.

Gao J, Aksoy B, Dogrusoz U, Dresdner G, Gross B, Sumer S . Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci Signal. 2013; 6(269):pl1. PMC: 4160307. DOI: 10.1126/scisignal.2004088. View

14.

Stambolic V, Suzuki A, de la Pompa J, Brothers G, Mirtsos C, Sasaki T . Negative regulation of PKB/Akt-dependent cell survival by the tumor suppressor PTEN. Cell. 1998; 95(1):29-39. DOI: 10.1016/s0092-8674(00)81780-8. View

15.

Maehama T, Dixon J . The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3,4,5-trisphosphate. J Biol Chem. 1998; 273(22):13375-8. DOI: 10.1074/jbc.273.22.13375. View

16.

Wu H, Lin Y, Liu C, Chung H, Wang Y, Lin Y . USP11 regulates PML stability to control Notch-induced malignancy in brain tumours. Nat Commun. 2014; 5:3214. PMC: 5645609. DOI: 10.1038/ncomms4214. View

17.

Gyorffy B . Discovery and ranking of the most robust prognostic biomarkers in serous ovarian cancer. Geroscience. 2023; 45(3):1889-1898. PMC: 10400493. DOI: 10.1007/s11357-023-00742-4. View

18.

Stephenson A, Smith A, Kattan M, Satagopan J, Reuter V, Scardino P . Integration of gene expression profiling and clinical variables to predict prostate carcinoma recurrence after radical prostatectomy. Cancer. 2005; 104(2):290-8. PMC: 1852494. DOI: 10.1002/cncr.21157. View

19.

Spatz A, Borg C, Feunteun J . X-chromosome genetics and human cancer. Nat Rev Cancer. 2004; 4(8):617-29. DOI: 10.1038/nrc1413. View

20.

Zhang J, Zhang P, Wei Y, Piao H, Wang W, Maddika S . Deubiquitylation and stabilization of PTEN by USP13. Nat Cell Biol. 2013; 15(12):1486-1494. PMC: 3951854. DOI: 10.1038/ncb2874. View