Molecular correlates and prognostic significance of SATB1 expression in colorectal cancer
Nodin, Björn LU ; Johannesson, Henrik ; Wangefjord, Sakarias LU ; O'Connor, Darran P. ; Ericson Lindquist, Kajsa LU ; Uhlen, Mathias ; Jirström, Karin LU
and Eberhard, Jakob
LU
(2012)
In Diagnostic Pathology
7(115).
- Abstract
- Background: Special AT-rich sequence-binding protein 1 (SATB1) is a global gene regulator that has been reported to confer malignant behavior and associate with poor prognosis in several cancer forms. SATB1 expression has been demonstrated to correlate with unfavourable tumour characteristics in rectal cancer, but its association with clinical outcome in colorectal cancer (CRC) remains unclear. In this study, we examined the prognostic impact of SATB1 expression in CRC, and its association with important molecular characteristics; i.e. beta-catenin overexpression, microsatellite instability (MSI) screening status, and SATB2 expression. Methods: Immunohistochemical expression of SATB1 and beta-catenin was assessed in tissue microarrays with... (More)
- Background: Special AT-rich sequence-binding protein 1 (SATB1) is a global gene regulator that has been reported to confer malignant behavior and associate with poor prognosis in several cancer forms. SATB1 expression has been demonstrated to correlate with unfavourable tumour characteristics in rectal cancer, but its association with clinical outcome in colorectal cancer (CRC) remains unclear. In this study, we examined the prognostic impact of SATB1 expression in CRC, and its association with important molecular characteristics; i.e. beta-catenin overexpression, microsatellite instability (MSI) screening status, and SATB2 expression. Methods: Immunohistochemical expression of SATB1 and beta-catenin was assessed in tissue microarrays with tumours from 529 incident CRC cases in the prospective population-based Malmo Diet and Cancer Study, previously analysed for SATB2 expression and MSI screening status. Spearman's Rho and Chi-Square tests were used to explore correlations between SATB1 expression, clinicopathological and investigative parameters. Kaplan Meier analysis and Cox proportional hazards modelling were used to explore the impact of SATB1 expression on cancer specific survival (CSS) and overall survival (OS). Results: SATB1 was expressed in 222 (42%) CRC cases and negative, or sparsely expressed, in adjacent colorectal mucosa (n = 16). SATB1 expression was significantly associated with microsatellite stable tumours (p < 0.001), beta-catenin overexpression (p < 0.001) and SATB2 expression (p < 0.001). While not prognostic in the full cohort, SATB1 expression was significantly associated with poor prognosis in SATB2 negative tumours (HR = 2.63; 95% CI 1.46-4.71; p(interaction) = 0.011 for CSS and HR = 2.31; 95% CI 1.32-4.04; p(interaction) = 0.015 for OS), remaining significant in multivariable analysis. Conclusions: The results of this study demonstrate that SATB1 expression in CRC is significantly associated with beta-catenin overexpression, microsatellite stability and SATB2 expression. Furthermore, SATB1 expression is a factor of poor prognosis in SATB2 negative tumours. Altogether, these data indicate an important role for SATB1 in colorectal carcinogenesis and suggest prognostically antagonistic effects of SATB1 and SATB2. The mechanistic basis for these observations warrants further study. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/3366378
- author
- Nodin, Björn
LU
; Johannesson, Henrik
; Wangefjord, Sakarias
LU
; O'Connor, Darran P.
; Ericson Lindquist, Kajsa
LU
; Uhlen, Mathias
; Jirström, Karin
LU
and Eberhard, Jakob
LU
- organization
- publishing date
- 2012
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Diagnostic Pathology
- volume
- 7
- issue
- 115
- publisher
- BioMed Central (BMC)
- external identifiers
-
- wos:000312601200001
- scopus:84865514469
- pmid:22935204
- ISSN
- 1746-1596
- DOI
- 10.1186/1746-1596-7-115
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Pathology, (Lund) (013030000), Oncology, MV (013035000)
- id
- b2a69ea0-837b-48b6-8d95-83ae8b58a9b1 (old id 3366378)
- date added to LUP
- 2016-04-01 14:04:10
- date last changed
- 2024-01-29 02:55:04
@article{b2a69ea0-837b-48b6-8d95-83ae8b58a9b1,
abstract = {{Background: Special AT-rich sequence-binding protein 1 (SATB1) is a global gene regulator that has been reported to confer malignant behavior and associate with poor prognosis in several cancer forms. SATB1 expression has been demonstrated to correlate with unfavourable tumour characteristics in rectal cancer, but its association with clinical outcome in colorectal cancer (CRC) remains unclear. In this study, we examined the prognostic impact of SATB1 expression in CRC, and its association with important molecular characteristics; i.e. beta-catenin overexpression, microsatellite instability (MSI) screening status, and SATB2 expression. Methods: Immunohistochemical expression of SATB1 and beta-catenin was assessed in tissue microarrays with tumours from 529 incident CRC cases in the prospective population-based Malmo Diet and Cancer Study, previously analysed for SATB2 expression and MSI screening status. Spearman's Rho and Chi-Square tests were used to explore correlations between SATB1 expression, clinicopathological and investigative parameters. Kaplan Meier analysis and Cox proportional hazards modelling were used to explore the impact of SATB1 expression on cancer specific survival (CSS) and overall survival (OS). Results: SATB1 was expressed in 222 (42%) CRC cases and negative, or sparsely expressed, in adjacent colorectal mucosa (n = 16). SATB1 expression was significantly associated with microsatellite stable tumours (p < 0.001), beta-catenin overexpression (p < 0.001) and SATB2 expression (p < 0.001). While not prognostic in the full cohort, SATB1 expression was significantly associated with poor prognosis in SATB2 negative tumours (HR = 2.63; 95% CI 1.46-4.71; p(interaction) = 0.011 for CSS and HR = 2.31; 95% CI 1.32-4.04; p(interaction) = 0.015 for OS), remaining significant in multivariable analysis. Conclusions: The results of this study demonstrate that SATB1 expression in CRC is significantly associated with beta-catenin overexpression, microsatellite stability and SATB2 expression. Furthermore, SATB1 expression is a factor of poor prognosis in SATB2 negative tumours. Altogether, these data indicate an important role for SATB1 in colorectal carcinogenesis and suggest prognostically antagonistic effects of SATB1 and SATB2. The mechanistic basis for these observations warrants further study.}},
author = {{Nodin, Björn and Johannesson, Henrik and Wangefjord, Sakarias and O'Connor, Darran P. and Ericson Lindquist, Kajsa and Uhlen, Mathias and Jirström, Karin and Eberhard, Jakob}},
issn = {{1746-1596}},
language = {{eng}},
number = {{115}},
publisher = {{BioMed Central (BMC)}},
series = {{Diagnostic Pathology}},
title = {{Molecular correlates and prognostic significance of SATB1 expression in colorectal cancer}},
url = {{https://lup.lub.lu.se/search/files/3761620/3894331.pdf}},
doi = {{10.1186/1746-1596-7-115}},
volume = {{7}},
year = {{2012}},
}