Low SMARCD3 expression is associated with poor prognosis in patients with prostate cancer.
SMARCD1
SMARCD3
SWI/SNF complex
prognostic marker
prostate cancer
Journal
The Prostate
ISSN: 1097-0045
Titre abrégé: Prostate
Pays: United States
ID NLM: 8101368
Informations de publication
Date de publication:
23 Oct 2024
23 Oct 2024
Historique:
revised:
04
09
2024
received:
31
10
2023
accepted:
09
10
2024
medline:
24
10
2024
pubmed:
24
10
2024
entrez:
23
10
2024
Statut:
aheadofprint
Résumé
SWI/SNF complexes represent a family of multi-subunit chromatin remodelers that are affected by alterations in >20% of human tumors. While mutations of SWI/SNF genes are relatively uncommon in prostate cancer (PCa), the literature suggests that deregulation of various subunits plays a role in prostate tumorigenesis. To assess SWI/SNF functions in a clinical context, we studied the mutually exclusive, paralogue accessory subunits SMARCD1, SMARCD2, and SMARCD3 that are included in every known complex and are sought to confer specificity. Performing immunohistochemistry (IHC), the protein levels of the SMARCD family members were measured using a tissue microarray (TMA) comprising malignant samples and matching healthy tissue of non-metastatic PCa patients (n = 168). Moreover, IHC was performed in castration-resistant tumors (n = 9) and lymph node metastases (n = 22). To assess their potential role as molecular biomarkers, SMARCD1 and SMARCD3 protein levels were correlated with clinical parameters such as T stage, Gleason score, biochemical recurrence, and progression-free survival. SMARCD1 protein levels in non-metastatic primary tumors, lymph node metastases, and castration-resistant samples were significantly higher than in benign tissues. Likewise, SMARCD3 protein expression was elevated in tumor tissue and especially lymph node metastases compared to benign samples. While SMARCD1 levels in primary tumors did not exhibit significant associations with any of the tested clinical parameters, SMARCD3 exhibited an inverse correlation with pre-operative PSA levels. Moreover, low SMARCD3 expression was associated with progression to metastasis. In congruence with previous literature, our results implicate that both SMARCD1 and SMARCD3 may exhibit relevant functions in the context of prostate tumorigenesis. Moreover, our approach suggests a potential role of SMARCD3 as a novel prognostic marker in clinically non-metastatic PCa.
Sections du résumé
BACKGROUNDS
BACKGROUND
SWI/SNF complexes represent a family of multi-subunit chromatin remodelers that are affected by alterations in >20% of human tumors. While mutations of SWI/SNF genes are relatively uncommon in prostate cancer (PCa), the literature suggests that deregulation of various subunits plays a role in prostate tumorigenesis. To assess SWI/SNF functions in a clinical context, we studied the mutually exclusive, paralogue accessory subunits SMARCD1, SMARCD2, and SMARCD3 that are included in every known complex and are sought to confer specificity.
METHODS
METHODS
Performing immunohistochemistry (IHC), the protein levels of the SMARCD family members were measured using a tissue microarray (TMA) comprising malignant samples and matching healthy tissue of non-metastatic PCa patients (n = 168). Moreover, IHC was performed in castration-resistant tumors (n = 9) and lymph node metastases (n = 22). To assess their potential role as molecular biomarkers, SMARCD1 and SMARCD3 protein levels were correlated with clinical parameters such as T stage, Gleason score, biochemical recurrence, and progression-free survival.
RESULTS
RESULTS
SMARCD1 protein levels in non-metastatic primary tumors, lymph node metastases, and castration-resistant samples were significantly higher than in benign tissues. Likewise, SMARCD3 protein expression was elevated in tumor tissue and especially lymph node metastases compared to benign samples. While SMARCD1 levels in primary tumors did not exhibit significant associations with any of the tested clinical parameters, SMARCD3 exhibited an inverse correlation with pre-operative PSA levels. Moreover, low SMARCD3 expression was associated with progression to metastasis.
CONCLUSIONS
CONCLUSIONS
In congruence with previous literature, our results implicate that both SMARCD1 and SMARCD3 may exhibit relevant functions in the context of prostate tumorigenesis. Moreover, our approach suggests a potential role of SMARCD3 as a novel prognostic marker in clinically non-metastatic PCa.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : "Margaretha-Hehberger-Stiftung", embedded in the "Medizinisch-Wissenschaftlicher Fonds des Bürgermeisters der Bundeshauptstadt Wien", Vienna, Austria
ID : 17083
Informations de copyright
© 2024 The Author(s). The Prostate published by Wiley Periodicals LLC.
Références
Hargreaves DC, Crabtree GR. ATP‐dependent chromatin remodeling: genetics, genomics and mechanisms. Cell Res. 2011;21(3):396‐420.
Euskirchen GM, Auerbach RK, Davidov E, et al. Diverse roles and interactions of the SWI/SNF chromatin remodeling complex revealed using global approaches. PLoS Genet. 2011;7(3):e1002008.
Euskirchen G, Auerbach RK, Snyder M. SWI/SNF chromatin‐remodeling factors: multiscale analyses and diverse functions. J Biol Chem. 2012;287(37):30897‐30905.
Kadoch C, Hargreaves DC, Hodges C, et al. Proteomic and bioinformatic analysis of mammalian SWI/SNF complexes identifies extensive roles in human malignancy. Nat Genet. 2013;45(6):592‐601.
Shain AH, Pollack JR. The spectrum of SWI/SNF mutations, ubiquitous in human cancers. PLoS ONE. 2013;8(1):e55119.
Lee RS, Roberts CWM. Linking the SWI/SNF complex to prostate cancer. Nat Genet. 2013;45(11):1268‐1269.
Sun A, Tawfik O, Gayed B, et al. Aberrant expression of SWI/SNF catalytic subunits BRG1/BRM is associated with tumor development and increased invasiveness in prostate cancers. Prostate. 2007;67(2):203‐213.
Heebøll S, Borre M, Ottosen PD, et al. SMARCC1 expression is upregulated in prostate cancer and positively correlated with tumour recurrence and dedifferentiation. Histol Histopathol. 2008;23(9):1069‐1076.
Balasubramaniam S, Comstock CES, Ertel A, et al. Aberrant BAF57 signaling facilitates prometastatic phenotypes. Clin Cancer Res. 2013;19(10):2657‐2667.
Hansen RL, Heeboll S, Ottosen PD, Dyrskjøt L, Borre M. Smarcc1 expression: a significant predictor of disease‐specific survival in patients with clinically localized prostate cancer treated with no intention to cure. Scand J Urol Nephrol. 2011;45(2):91‐96.
Ertl IE, Brettner R, Kronabitter H, et al. The SMARCD family of SWI/SNF accessory proteins is involved in the transcriptional regulation of androgen receptor‐driven genes and plays a role in various essential processes of prostate cancer. Cells. 2022;12(1):124.
Weissman B, Knudsen KE. Hijacking the chromatin remodeling machinery: impact of SWI/SNF perturbations in cancer. Cancer Res. 2009;69(21):8223‐8230.
Michel BC, D'Avino AR, Cassel SH, et al. A non‐canonical SWI/SNF complex is a synthetic lethal target in cancers driven by BAF complex perturbation. Nat Cell Biol. 2018;20(12):1410‐1420.
Cerami E, Gao J, Dogrusoz U, et al. The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discov. 2012;2(5):401‐404.
Gao J, Aksoy BA, Dogrusoz U, et al. u. a. Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci Signaling. 2013;6(269):pl1.
Humphrey PA. Gleason grading and prognostic factors in carcinoma of the prostate. Mod Pathol. 2004;17(3):292‐306.
Kim M, Yoo D, Pyo J, Cho W. Clinicopathological significances of positive surgical resection margin after radical prostatectomy for prostatic cancers: a meta‐analysis. Medicina. 2022;58(9):1251.
Shahabi A, Satkunasivam R, Gill IS, et al. Predictors of time to biochemical recurrence in a radical prostatectomy cohort within the PSA‐era. Can Urol Assoc J. 2016;10(1‐2):17.
Ro YK, Lee S, Jeong CW, Hong SK, Byun SS, Lee SE. Biochemical recurrence in Gleason score 7 prostate cancer in Korean men: significance of the primary Gleason grade. Korean J Urol. 2012;53(12):826‐829.
Prensner JR, Iyer MK, Sahu A, et al. The long noncoding RNA SChLAP1 promotes aggressive prostate cancer and antagonizes the SWI/SNF complex. Nat Genet. 2013;45(11):1392‐1398.
Mota STS, Vecchi L, Zóia MAP, et al. New insights into the role of polybromo‐1 in prostate cancer. Int J Mol Sci. 2019;20(12):2852.
Cyrta J, Augspach A, De Filippo MR, et al. Role of specialized composition of SWI/SNF complexes in prostate cancer lineage plasticity. Nat Commun. 2020;11(1):5549.
Xiao L, Parolia A, Qiao Y, et al. Targeting SWI/SNF ATPases in enhancer‐addicted prostate cancer. Nature. 2022;601(7893):434‐439.
Shen H, Powers N, Saini N, et al. The SWI/SNF ATPase brm is a gatekeeper of proliferative control in prostate cancer. Cancer Res. 2008;68(24):10154‐10162.
Dai Y, Ngo D, Jacob J, Forman LW, Faller DV. Prohibitin and the SWI/SNF ATPase subunit BRG1 are required for effective androgen antagonist‐mediated transcriptional repression of androgen receptor‐regulated genes. Carcinogenesis. 2008;29(9):1725‐1733.
Sun D, Lee YS, Malhotra A, et al. miR‐99 family of microRNAs suppresses the expression of prostate specific antigen and prostate cancer cell proliferation. Cancer Res. 2011;71(4):1313‐1324.
Luke MC, Coffey DS. Human androgen receptor binding to the androgen response element of prostate specific antigen. J Androl. 1994;15(1):41‐51.
Li R, Wheeler T, Dai H, Frolov A, Thompson T, Ayala G. High level of androgen receptor is associated with aggressive clinicopathologic features and decreased biochemical recurrence‐free survival in prostate: cancer patients treated with radical prostatectomy. Am J Surg Pathol. 2004;28(7):928‐934.
Henshall SM, Quinn DI, Lee CS, et al. Altered expression of androgen receptor in the malignant epithelium and adjacent stroma is associated with early relapse in prostate cancer. Cancer Res. 2001;61(2):423‐427.
Hashmi AA, Mudassir G, Irfan M, et al. Prognostic significance of high androgen receptor expression in prostatic acinar adenocarcinoma. Asian Pac J Cancer Prev. 2019;20(3):893‐896.
Arora K, Barbieri CE. Molecular subtypes of prostate cancer. Curr Oncol Rep. 2018;20(8):58.
Bahmad HF, Jalloul M, Azar J, et al. Tumor microenvironment in prostate cancer: toward identification of novel molecular biomarkers for diagnosis, prognosis, and therapy development. Front Genet. 2021;12. doi:10.3389/fgene.2021.652747
Zong S, Gao J. Identifying the tumor immune microenvironment‐associated prognostic genes for prostate cancer. Discov Oncol. 2024;15(1):42.
Sun X, Wang L, Li H, et al. Identification of microenvironment related potential biomarkers of biochemical recurrence at 3 years after prostatectomy in prostate adenocarcinoma. Aging. 2021;13(12):16024‐16042.