Expression of transglutaminase-2 (TGM2) in the prognosis of female invasive breast cancer

Fiona M. Blows; H. Raza Ali; Wei Cope; Paul D. P. Pharoah; Claire V. S. Pike; Elena Provenzano; Peter Coussons

doi:10.1038/s44276-023-00030-w

Expression of transglutaminase-2 (TGM2) in the prognosis of female invasive breast cancer

Fiona M. Blows
, H. Raza Ali
, Wei Cope
, Paul D. P. Pharoah
, Claire V. S. Pike
, Elena Provenzano
, Peter Coussons

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Abstract

Background: Transglutaminase 2 (TGM2) is a protein expressed in several isoforms in both intra- and extra-cellular tissue compartments. It has multiple functions that are important in cancer biology and several small studies have suggested expression of TGM2 in breast cancers is associated with a poorer prognosis. The aim of this study was to evaluate the role of intra-cellular and extra-cellular TGM2 expression in breast cancer and to determine whether there were any differences by hormone receptor status.

Methods: We carried out TGM2 immunostaining of tissue micro-arrays comprising 2169 tumour cores and scored these for both intra- and extra-cellular and expression.

Results: Intra-cellular (tumour cell) TGM2 positivity was associated with a better prognosis (HR = 0.74, 95% CI 0.59–0.92) with a larger effect stronger in hormone-receptor-negative cases (HR = 0.56, 95% CI 0.37–0.85). Extra-cellular (stromal) TGM2 expression was associated with a poorer prognosis (HR = 1.47, 95% CI 1.06–2.03) with a stronger association in hormone-receptor-positive cases (HR = 1.60, 95% CI 1.09–2.34).

Conclusion: Tissue compartment and hormone receptor status differences in the effect of TGM2 expression on clinical outcomes of breast cancer may reflect the different functions of TGM2.

Original language	English
Article number	5
Journal	BJC Reports
Volume	2
DOIs	https://doi.org/10.1038/s44276-023-00030-w
Publication status	Published - 24 Jan 2024

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This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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Cite this

@article{418910ff84bf4c0fbdeaf57363be2975,

title = "Expression of transglutaminase-2 (TGM2) in the prognosis of female invasive breast cancer",

abstract = "Background: Transglutaminase 2 (TGM2) is a protein expressed in several isoforms in both intra- and extra-cellular tissue compartments. It has multiple functions that are important in cancer biology and several small studies have suggested expression of TGM2 in breast cancers is associated with a poorer prognosis. The aim of this study was to evaluate the role of intra-cellular and extra-cellular TGM2 expression in breast cancer and to determine whether there were any differences by hormone receptor status. Methods: We carried out TGM2 immunostaining of tissue micro-arrays comprising 2169 tumour cores and scored these for both intra- and extra-cellular and expression. Results: Intra-cellular (tumour cell) TGM2 positivity was associated with a better prognosis (HR = 0.74, 95\% CI 0.59{\textendash}0.92) with a larger effect stronger in hormone-receptor-negative cases (HR = 0.56, 95\% CI 0.37{\textendash}0.85). Extra-cellular (stromal) TGM2 expression was associated with a poorer prognosis (HR = 1.47, 95\% CI 1.06{\textendash}2.03) with a stronger association in hormone-receptor-positive cases (HR = 1.60, 95\% CI 1.09{\textendash}2.34). Conclusion: Tissue compartment and hormone receptor status differences in the effect of TGM2 expression on clinical outcomes of breast cancer may reflect the different functions of TGM2.",

author = "Blows, \{Fiona M.\} and Ali, \{H. Raza\} and Wei Cope and Pharoah, \{Paul D. P.\} and Pike, \{Claire V. S.\} and Elena Provenzano and Peter Coussons",

note = "Data availability: The data and analysis code (R script) to reproduce the results reported in this manuscript are available from the corresponding author on request. Funding information: SEARCH was funded by Cancer Research UK (C490/A10119 C490/A10124 C490/A16561). This work was supported by the National Institute for Health Research Biomedical Research Centre at the University of Cambridge.",

year = "2024",

month = jan,

day = "24",

doi = "10.1038/s44276-023-00030-w",

language = "English",

volume = "2",

journal = "BJC Reports",

issn = "2731-9377",

publisher = "Springer Nature",

}

TY - JOUR

T1 - Expression of transglutaminase-2 (TGM2) in the prognosis of female invasive breast cancer

AU - Blows, Fiona M.

AU - Ali, H. Raza

AU - Cope, Wei

AU - Pharoah, Paul D. P.

AU - Pike, Claire V. S.

AU - Provenzano, Elena

AU - Coussons, Peter

N1 - Data availability: The data and analysis code (R script) to reproduce the results reported in this manuscript are available from the corresponding author on request. Funding information: SEARCH was funded by Cancer Research UK (C490/A10119 C490/A10124 C490/A16561). This work was supported by the National Institute for Health Research Biomedical Research Centre at the University of Cambridge.

PY - 2024/1/24

Y1 - 2024/1/24

N2 - Background: Transglutaminase 2 (TGM2) is a protein expressed in several isoforms in both intra- and extra-cellular tissue compartments. It has multiple functions that are important in cancer biology and several small studies have suggested expression of TGM2 in breast cancers is associated with a poorer prognosis. The aim of this study was to evaluate the role of intra-cellular and extra-cellular TGM2 expression in breast cancer and to determine whether there were any differences by hormone receptor status. Methods: We carried out TGM2 immunostaining of tissue micro-arrays comprising 2169 tumour cores and scored these for both intra- and extra-cellular and expression. Results: Intra-cellular (tumour cell) TGM2 positivity was associated with a better prognosis (HR = 0.74, 95% CI 0.59–0.92) with a larger effect stronger in hormone-receptor-negative cases (HR = 0.56, 95% CI 0.37–0.85). Extra-cellular (stromal) TGM2 expression was associated with a poorer prognosis (HR = 1.47, 95% CI 1.06–2.03) with a stronger association in hormone-receptor-positive cases (HR = 1.60, 95% CI 1.09–2.34). Conclusion: Tissue compartment and hormone receptor status differences in the effect of TGM2 expression on clinical outcomes of breast cancer may reflect the different functions of TGM2.

AB - Background: Transglutaminase 2 (TGM2) is a protein expressed in several isoforms in both intra- and extra-cellular tissue compartments. It has multiple functions that are important in cancer biology and several small studies have suggested expression of TGM2 in breast cancers is associated with a poorer prognosis. The aim of this study was to evaluate the role of intra-cellular and extra-cellular TGM2 expression in breast cancer and to determine whether there were any differences by hormone receptor status. Methods: We carried out TGM2 immunostaining of tissue micro-arrays comprising 2169 tumour cores and scored these for both intra- and extra-cellular and expression. Results: Intra-cellular (tumour cell) TGM2 positivity was associated with a better prognosis (HR = 0.74, 95% CI 0.59–0.92) with a larger effect stronger in hormone-receptor-negative cases (HR = 0.56, 95% CI 0.37–0.85). Extra-cellular (stromal) TGM2 expression was associated with a poorer prognosis (HR = 1.47, 95% CI 1.06–2.03) with a stronger association in hormone-receptor-positive cases (HR = 1.60, 95% CI 1.09–2.34). Conclusion: Tissue compartment and hormone receptor status differences in the effect of TGM2 expression on clinical outcomes of breast cancer may reflect the different functions of TGM2.

U2 - 10.1038/s44276-023-00030-w

DO - 10.1038/s44276-023-00030-w

M3 - Article

SN - 2731-9377

VL - 2

JO - BJC Reports

JF - BJC Reports

M1 - 5

ER -