Overexpression of the novel senescence marker β-galactosidase (GLB1) in prostate cancer predicts reduced PSA recurrence

Jennifer Wagner, Nathan Damaschke, Bing Yang, Matthew Truong, Chad Guenther, Johnathon McCormick, Wei Huang, David Jarrard

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Purpose: Senescence is a terminal growth arrest that functions as a tumor suppressor in aging and precancerous cells and is a response to selected anticancer compounds. Lysosomal-β-galactosidase (GLB1) hydrolyzes β-galactose from glycoconjugates and is the origin of senescence-associated β-gal activity (SA-β-gal). Using a new GLB1 antibody, senescence biology was investigated in prostate cancer (PCa) tissues. Experimental Design: In vitro characterization of GLB1 was determined in primary prostate epithelial cell cultures passaged to replicative senescence and in therapy-induced senescence in PCa lines using chemotherapeutic agents. FFPE tissue microarrays were subjected to immunofluorescent staining for GLB1, Ki67 and HP1γ and automated quantitative imaging initially using AQUA in exploratory samples and Vectra in a validation series. Results: GLB1 expression accumulates in replicative and induced senescence and correlates with senescent morphology and P16 (CDKN2) expression. In tissue arrays, quantitative imaging detects increased GLB1 expression in high-grade prostatic intraepithelial neoplasia (HGPIN), known to contain senescent cells, and cancer compared to benign prostate tissues (p<0.01) and senescent cells contain low Ki67 and elevated HP1γ. Within primary tumors, elevated GLB1 associates with lower T stage (p=0.01), localized versus metastatic disease (p=0.0003) and improved PSA-free survival (p=0.03). Increased GLB1 stratifies better PSA-free survival in intermediate grade PCa (0.01). Tissues that elaborate higher GLB1 display increased uniformity of expression. Conclusion: Increased GLB1 is a valuable marker in formalin-fixed paraffin-embedded (FFPE) tissues for the senescence-like phenotype and associates with improved cancer outcomes. This protein addresses a lack of senescence markers and should be applicable to study the biologic role of senescence in other cancers.

Original languageEnglish (US)
Article numbere0124366
JournalPloS one
Volume10
Issue number4
DOIs
StatePublished - Apr 15 2015
Externally publishedYes

Fingerprint

Galactosidases
galactosidases
prostatic neoplasms
Prostatic Neoplasms
Tissue
Recurrence
neoplasms
Cell Aging
formalin
Paraffin
alkanes
Formaldehyde
Neoplasms
Tumors
Prostate
image analysis
Imaging techniques
glycoconjugates
Glycoconjugates
Prostatic Intraepithelial Neoplasia

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Overexpression of the novel senescence marker β-galactosidase (GLB1) in prostate cancer predicts reduced PSA recurrence. / Wagner, Jennifer; Damaschke, Nathan; Yang, Bing; Truong, Matthew; Guenther, Chad; McCormick, Johnathon; Huang, Wei; Jarrard, David.

In: PloS one, Vol. 10, No. 4, e0124366, 15.04.2015.

Research output: Contribution to journalArticle

Wagner, Jennifer ; Damaschke, Nathan ; Yang, Bing ; Truong, Matthew ; Guenther, Chad ; McCormick, Johnathon ; Huang, Wei ; Jarrard, David. / Overexpression of the novel senescence marker β-galactosidase (GLB1) in prostate cancer predicts reduced PSA recurrence. In: PloS one. 2015 ; Vol. 10, No. 4.
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abstract = "Purpose: Senescence is a terminal growth arrest that functions as a tumor suppressor in aging and precancerous cells and is a response to selected anticancer compounds. Lysosomal-β-galactosidase (GLB1) hydrolyzes β-galactose from glycoconjugates and is the origin of senescence-associated β-gal activity (SA-β-gal). Using a new GLB1 antibody, senescence biology was investigated in prostate cancer (PCa) tissues. Experimental Design: In vitro characterization of GLB1 was determined in primary prostate epithelial cell cultures passaged to replicative senescence and in therapy-induced senescence in PCa lines using chemotherapeutic agents. FFPE tissue microarrays were subjected to immunofluorescent staining for GLB1, Ki67 and HP1γ and automated quantitative imaging initially using AQUA in exploratory samples and Vectra in a validation series. Results: GLB1 expression accumulates in replicative and induced senescence and correlates with senescent morphology and P16 (CDKN2) expression. In tissue arrays, quantitative imaging detects increased GLB1 expression in high-grade prostatic intraepithelial neoplasia (HGPIN), known to contain senescent cells, and cancer compared to benign prostate tissues (p<0.01) and senescent cells contain low Ki67 and elevated HP1γ. Within primary tumors, elevated GLB1 associates with lower T stage (p=0.01), localized versus metastatic disease (p=0.0003) and improved PSA-free survival (p=0.03). Increased GLB1 stratifies better PSA-free survival in intermediate grade PCa (0.01). Tissues that elaborate higher GLB1 display increased uniformity of expression. Conclusion: Increased GLB1 is a valuable marker in formalin-fixed paraffin-embedded (FFPE) tissues for the senescence-like phenotype and associates with improved cancer outcomes. This protein addresses a lack of senescence markers and should be applicable to study the biologic role of senescence in other cancers.",
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AU - Wagner, Jennifer

AU - Damaschke, Nathan

AU - Yang, Bing

AU - Truong, Matthew

AU - Guenther, Chad

AU - McCormick, Johnathon

AU - Huang, Wei

AU - Jarrard, David

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