STAG2 Protein Expression in Non-muscle-invasive Bladder Cancer: Associations with Sex, Genomic and Transcriptomic Changes, and Clinical Outcomes

Naheema S Gordon; Nada Humayun-Zakaria; Anshita Goel; Ben Abbotts; Maurice P Zeegers; K K Cheng; Nicholas D James; Roland Arnold; Richard T Bryan; Douglas G Ward

doi:10.1016/j.euros.2022.02.004

STAG2 Protein Expression in Non-muscle-invasive Bladder Cancer: Associations with Sex, Genomic and Transcriptomic Changes, and Clinical Outcomes

Naheema S Gordon, Nada Humayun-Zakaria, Anshita Goel, Ben Abbotts, Maurice P Zeegers, K K Cheng, Nicholas D James, Roland Arnold, Richard T Bryan, Douglas G Ward^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Background: Mutations in STAG2 cause complete loss of STAG2 protein in approximately one-third of non-muscle-invasive bladder cancers (NMIBCs). STAG2 protein expression is easily determined via immunohistochemistry (IHC) and published data suggest that loss of STAG2 expression is a good prognostic indicator in NMIBC.

Objective: To confirm the relationship between STAG2 protein expression and clinical outcomes and tumour characteristics in NMIBC.

Design setting and participants: IHC was used to determine STAG2 expression in 748 incident urothelial bladder cancers (UBCs) and recurrence-free, progression-free, and disease-specific survival were compared for patients with and without STAG2 loss. Exome and RNA sequencing were used to explore links between STAG2 loss and tumour molecular characteristics.

Results and limitations: STAG2 loss was observed in 19% of UBC patients and was 1.6-fold more common among female patients. Loss was frequent among grade 1 pTa tumours (40%), decreasing with stage and grade to only 5% among grade 3 pT2+ tumours. Loss was associated with fewer copy-number changes and less aggressive expression subtypes. In UBC, STAG2 loss was a highly significant prognostic indicator of better disease-free survival but was not independent of stage and grade. STAG2 loss was not a statistically significant predictor of NMIBC recurrence. STAG2 loss was significantly associated with better progression-free survival in NMIBC and appeared to be more prognostic for males than for females.

Conclusions: A simple IHC-based STAG2 test shows promise for identifying NMIBC patients at lower risk of progression to MIBC for whom more conservative treatments may be suitable.

Patient summary: A protein called STAG2 is frequently lost in early bladder cancers, most often in less aggressive tumours. STAG2 loss is easily measured and could be used as a biomarker to help guide treatment decisions.

Original language	English
Pages (from-to)	88-95
Number of pages	8
Journal	European urology open science
Volume	38
DOIs	https://doi.org/10.1016/j.euros.2022.02.004
Publication status	Published - Apr 2022

Keywords

Biomarker
Bladder cancer
PROGRESSION
Prognosis
STAG2
SUBTYPES
TUMOR-SUPPRESSOR STAG2

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Gordon, N. S., Humayun-Zakaria, N., Goel, A., Abbotts, B., Zeegers, M. P., Cheng, K. K., James, N. D., Arnold, R., Bryan, R. T., & Ward, D. G. (2022). STAG2 Protein Expression in Non-muscle-invasive Bladder Cancer: Associations with Sex, Genomic and Transcriptomic Changes, and Clinical Outcomes. European urology open science, 38, 88-95. https://doi.org/10.1016/j.euros.2022.02.004

@article{22b69ee0f7724b9cb85608c7010816ba,

title = "STAG2 Protein Expression in Non-muscle-invasive Bladder Cancer: Associations with Sex, Genomic and Transcriptomic Changes, and Clinical Outcomes",

abstract = "Background: Mutations in STAG2 cause complete loss of STAG2 protein in approximately one-third of non-muscle-invasive bladder cancers (NMIBCs). STAG2 protein expression is easily determined via immunohistochemistry (IHC) and published data suggest that loss of STAG2 expression is a good prognostic indicator in NMIBC.Objective: To confirm the relationship between STAG2 protein expression and clinical outcomes and tumour characteristics in NMIBC.Design setting and participants: IHC was used to determine STAG2 expression in 748 incident urothelial bladder cancers (UBCs) and recurrence-free, progression-free, and disease-specific survival were compared for patients with and without STAG2 loss. Exome and RNA sequencing were used to explore links between STAG2 loss and tumour molecular characteristics.Results and limitations: STAG2 loss was observed in 19% of UBC patients and was 1.6-fold more common among female patients. Loss was frequent among grade 1 pTa tumours (40%), decreasing with stage and grade to only 5% among grade 3 pT2+ tumours. Loss was associated with fewer copy-number changes and less aggressive expression subtypes. In UBC, STAG2 loss was a highly significant prognostic indicator of better disease-free survival but was not independent of stage and grade. STAG2 loss was not a statistically significant predictor of NMIBC recurrence. STAG2 loss was significantly associated with better progression-free survival in NMIBC and appeared to be more prognostic for males than for females.Conclusions: A simple IHC-based STAG2 test shows promise for identifying NMIBC patients at lower risk of progression to MIBC for whom more conservative treatments may be suitable.Patient summary: A protein called STAG2 is frequently lost in early bladder cancers, most often in less aggressive tumours. STAG2 loss is easily measured and could be used as a biomarker to help guide treatment decisions.",

keywords = "Biomarker, Bladder cancer, PROGRESSION, Prognosis, STAG2, SUBTYPES, TUMOR-SUPPRESSOR STAG2",

author = "Gordon, {Naheema S} and Nada Humayun-Zakaria and Anshita Goel and Ben Abbotts and Zeegers, {Maurice P} and Cheng, {K K} and James, {Nicholas D} and Roland Arnold and Bryan, {Richard T} and Ward, {Douglas G}",

note = "{\textcopyright} 2022 The Authors.",

year = "2022",

month = apr,

doi = "10.1016/j.euros.2022.02.004",

language = "English",

volume = "38",

pages = "88--95",

journal = "European urology open science",

issn = "2666-1683",

publisher = "Elsevier B.V.",

}

TY - JOUR

T1 - STAG2 Protein Expression in Non-muscle-invasive Bladder Cancer

T2 - Associations with Sex, Genomic and Transcriptomic Changes, and Clinical Outcomes

AU - Gordon, Naheema S

AU - Humayun-Zakaria, Nada

AU - Goel, Anshita

AU - Abbotts, Ben

AU - Zeegers, Maurice P

AU - Cheng, K K

AU - James, Nicholas D

AU - Arnold, Roland

AU - Bryan, Richard T

AU - Ward, Douglas G

PY - 2022/4

Y1 - 2022/4

N2 - Background: Mutations in STAG2 cause complete loss of STAG2 protein in approximately one-third of non-muscle-invasive bladder cancers (NMIBCs). STAG2 protein expression is easily determined via immunohistochemistry (IHC) and published data suggest that loss of STAG2 expression is a good prognostic indicator in NMIBC.Objective: To confirm the relationship between STAG2 protein expression and clinical outcomes and tumour characteristics in NMIBC.Design setting and participants: IHC was used to determine STAG2 expression in 748 incident urothelial bladder cancers (UBCs) and recurrence-free, progression-free, and disease-specific survival were compared for patients with and without STAG2 loss. Exome and RNA sequencing were used to explore links between STAG2 loss and tumour molecular characteristics.Results and limitations: STAG2 loss was observed in 19% of UBC patients and was 1.6-fold more common among female patients. Loss was frequent among grade 1 pTa tumours (40%), decreasing with stage and grade to only 5% among grade 3 pT2+ tumours. Loss was associated with fewer copy-number changes and less aggressive expression subtypes. In UBC, STAG2 loss was a highly significant prognostic indicator of better disease-free survival but was not independent of stage and grade. STAG2 loss was not a statistically significant predictor of NMIBC recurrence. STAG2 loss was significantly associated with better progression-free survival in NMIBC and appeared to be more prognostic for males than for females.Conclusions: A simple IHC-based STAG2 test shows promise for identifying NMIBC patients at lower risk of progression to MIBC for whom more conservative treatments may be suitable.Patient summary: A protein called STAG2 is frequently lost in early bladder cancers, most often in less aggressive tumours. STAG2 loss is easily measured and could be used as a biomarker to help guide treatment decisions.

AB - Background: Mutations in STAG2 cause complete loss of STAG2 protein in approximately one-third of non-muscle-invasive bladder cancers (NMIBCs). STAG2 protein expression is easily determined via immunohistochemistry (IHC) and published data suggest that loss of STAG2 expression is a good prognostic indicator in NMIBC.Objective: To confirm the relationship between STAG2 protein expression and clinical outcomes and tumour characteristics in NMIBC.Design setting and participants: IHC was used to determine STAG2 expression in 748 incident urothelial bladder cancers (UBCs) and recurrence-free, progression-free, and disease-specific survival were compared for patients with and without STAG2 loss. Exome and RNA sequencing were used to explore links between STAG2 loss and tumour molecular characteristics.Results and limitations: STAG2 loss was observed in 19% of UBC patients and was 1.6-fold more common among female patients. Loss was frequent among grade 1 pTa tumours (40%), decreasing with stage and grade to only 5% among grade 3 pT2+ tumours. Loss was associated with fewer copy-number changes and less aggressive expression subtypes. In UBC, STAG2 loss was a highly significant prognostic indicator of better disease-free survival but was not independent of stage and grade. STAG2 loss was not a statistically significant predictor of NMIBC recurrence. STAG2 loss was significantly associated with better progression-free survival in NMIBC and appeared to be more prognostic for males than for females.Conclusions: A simple IHC-based STAG2 test shows promise for identifying NMIBC patients at lower risk of progression to MIBC for whom more conservative treatments may be suitable.Patient summary: A protein called STAG2 is frequently lost in early bladder cancers, most often in less aggressive tumours. STAG2 loss is easily measured and could be used as a biomarker to help guide treatment decisions.

KW - Biomarker

KW - Bladder cancer

KW - PROGRESSION

KW - Prognosis

KW - STAG2

KW - SUBTYPES

KW - TUMOR-SUPPRESSOR STAG2

U2 - 10.1016/j.euros.2022.02.004

DO - 10.1016/j.euros.2022.02.004

M3 - Article

C2 - 35495284

SN - 2666-1683

VL - 38

SP - 88

EP - 95

JO - European urology open science

JF - European urology open science

ER -

STAG2 Protein Expression in Non-muscle-invasive Bladder Cancer: Associations with Sex, Genomic and Transcriptomic Changes, and Clinical Outcomes

Abstract

Keywords

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