CDX2 and SATB2 loss are associated with myeloid cell infiltration and poor survival in colorectal cancer
Sirniö, Päivi; Elomaa, Hanna; Tuomisto, Anne; Äijälä, Ville K; Karjalainen, Henna; Kastinen, Meeri; Tapiainen, Vilja V; Sirkiä, Onni; Ahtiainen, Maarit; Helminen, Olli; Wirta, Erkki-Ville; Rintala, Jukka; Meriläinen, Sanna; Saarnio, Juha; Rautio, Tero; Seppälä, Toni T; Böhm, Jan; Mecklin, Jukka-Pekka; Mäkinen, Markus J; Väyrynen, Juha P (2025-02-25)
Springer
25.02.2025
Sirniö, P., Elomaa, H., Tuomisto, A. et al. CDX2 and SATB2 loss are associated with myeloid cell infiltration and poor survival in colorectal cancer. Cancer Immunol Immunother 74, 111 (2025). https://doi.org/10.1007/s00262-025-03964-x
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© The Author(s) 2025. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
https://creativecommons.org/licenses/by/4.0/
© The Author(s) 2025. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
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Julkaisun pysyvä osoite on
https://urn.fi/URN:NBN:fi:oulu-202502261839
https://urn.fi/URN:NBN:fi:oulu-202502261839
Tiivistelmä
Abstract
Background:
Caudal-type homeobox 2 (CDX2) and special AT-rich sequence-binding protein 2 (SATB2) are transcription factors playing important roles in intestinal homeostasis and participating in the regulation of intestinal inflammation. In colorectal cancer (CRC), reduced expression levels of CDX2 and SATB2 have been associated with poor differentiation and worse survival. However, their prognostic significance still needs further clarification, and the associations between CDX2 and SATB2 and immune cell infiltration into the CRC microenvironment are largely unknown.
Methods:
We analyzed CDX2 and SATB2 expression in two large cohorts of stages I–IV CRC patients (N = 2302) and analyzed their associations with clinicopathologic parameters, the density of local immune cells (determined with three multiplex immunohistochemistry panels and conventional immunohistochemistry), and survival.
Results:
In mismatch repair-proficient tumors, reduced CDX2 and SATB2 expression were associated with higher densities of immature monocytic cells, macrophages, and M2-like macrophages. Low expression of CDX2 was associated with shorter cancer-specific survival independent of conventional prognostic parameters in both cohorts. In the larger cohort, adjusted hazard ratio (HR) for negative (vs. high) CDX2 expression was 3.62 (95% CI 2.08–6.31, ptrend < 0.0001), and adjusted HR for negative (vs. high) SATB2 level was 1.61 (95% CI 0.97–2.67, ptrend = 0.002).
Conclusion:
This study indicates that reduced CDX2 and SATB2 expression levels are associated with myeloid cell infiltration in the CRC microenvironment and represent markers for poor outcome. These findings highlight the potential of CDX2 and SATB2 as biomarkers for classifying CRC patients and support their role in regulating the tumor microenvironment.
Background:
Caudal-type homeobox 2 (CDX2) and special AT-rich sequence-binding protein 2 (SATB2) are transcription factors playing important roles in intestinal homeostasis and participating in the regulation of intestinal inflammation. In colorectal cancer (CRC), reduced expression levels of CDX2 and SATB2 have been associated with poor differentiation and worse survival. However, their prognostic significance still needs further clarification, and the associations between CDX2 and SATB2 and immune cell infiltration into the CRC microenvironment are largely unknown.
Methods:
We analyzed CDX2 and SATB2 expression in two large cohorts of stages I–IV CRC patients (N = 2302) and analyzed their associations with clinicopathologic parameters, the density of local immune cells (determined with three multiplex immunohistochemistry panels and conventional immunohistochemistry), and survival.
Results:
In mismatch repair-proficient tumors, reduced CDX2 and SATB2 expression were associated with higher densities of immature monocytic cells, macrophages, and M2-like macrophages. Low expression of CDX2 was associated with shorter cancer-specific survival independent of conventional prognostic parameters in both cohorts. In the larger cohort, adjusted hazard ratio (HR) for negative (vs. high) CDX2 expression was 3.62 (95% CI 2.08–6.31, ptrend < 0.0001), and adjusted HR for negative (vs. high) SATB2 level was 1.61 (95% CI 0.97–2.67, ptrend = 0.002).
Conclusion:
This study indicates that reduced CDX2 and SATB2 expression levels are associated with myeloid cell infiltration in the CRC microenvironment and represent markers for poor outcome. These findings highlight the potential of CDX2 and SATB2 as biomarkers for classifying CRC patients and support their role in regulating the tumor microenvironment.
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