Dataset Information

The Prognostic and Predictive Utility of CDX2 in Colorectal Cancer.

ABSTRACT: Caudal type homeobox transcription factor 2 (CDX2) is a gastrointestinal cancer biomarker that regulates epithelial development and differentiation. Absence or low levels of CDX2 have been associated with poor prognosis and proposed as a chemotherapy response predictor. Tumour tissue samples from 668 patients with stage I-IV colorectal cancer were stained for CDX2 and stratified into two subgroups according to expression levels. Statistical tests were used to evaluate CDX2's relationship with survival and chemotherapy response. Of 646 samples successfully stained, 51 (7.9%) had low CDX2 levels, and 595 (92.1%) had high levels. Low CDX2 staining was associated with poor differentiation and the presence of lymphovascular or perineural invasion and was more common in colon and right-sided tumours. Overall survival (p < 0.001) and disease-free survival (p = 0.009) were reduced in patients with low CDX2 expression. Multivariable analysis validated CDX2 as an independent poor prognostic factor after excluding confounding variables. There was no statistically significant improvement in survival with adjuvant chemotherapy in stage II colon cancer (p = 0.11). In the rectal cohort, there was no relationship between CDX2 levels and therapy response. While confirming the prognostic utility of CDX2 in colorectal cancer, our study highlights that larger studies are required to confirm its utility as a predictive chemotherapy biomarker, especially in left-sided and rectal cancers.

SUBMITTER: Chan WY

PROVIDER: S-EPMC11354371 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature

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The Prognostic and Predictive Utility of CDX2 in Colorectal Cancer.

Chan Wei Yen WY Chua Wei W Wilkinson Kate K Epitakaduwa Chandika C Mandaliya Hiren H Descallar Joseph J Roberts Tara Laurine TL Becker Therese Maria TM Ng Weng W Lee Cheok Soon CS Lim Stephanie Hui-Su SH

International journal of molecular sciences 20240808 16

Caudal type homeobox transcription factor 2 (CDX2) is a gastrointestinal cancer biomarker that regulates epithelial development and differentiation. Absence or low levels of CDX2 have been associated with poor prognosis and proposed as a chemotherapy response predictor. Tumour tissue samples from 668 patients with stage I-IV colorectal cancer were stained for CDX2 and stratified into two subgroups according to expression levels. Statistical tests were used to evaluate CDX2's relationship with su ...[more]

PMID: 39201360

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Project description:BackgroundStudies have confirmed that Caudal Type Homeobox 2 (CDX2) plays a tumor suppressor role in colorectal cancer (CRC) and as a prognostic and predictive marker for colorectal cancer. The epithelial to mesenchymal transition (EMT) is a transdifferentiation process, providing migratory and invasive properties to cancer cells during tumor progression. However, the role of CDX2 during the activation of EMT in CRC maintains controversial.AimTo investigate whether CDX2 is associated with EMT in CRC.MethodsForty-six CRC patients were included in the study. Expressions of CDX2, E-cadherin, and N-cadherin in all CRC patients were detected by IHC. ROC assays were applied to detect cut-off points for IHC scores to distinguish high and low expressions of CDX2 in 46 CRC samples. The prognostic value of CDX2 was statistically analyzed. MTT, Western blot, invasion, and migration assays in vitro were employed to explore the function of CDX2.ResultsWe observed that high expressions of CDX2 and E-cadherin as well as low expressions of N-cadherin were significantly correlated with favorable prognosis. The levels of CDX2 protein exhibited a positive associated with E-cadherin while negative correlation with N-cadherin. Then, the low expression of CDX2 and high expression of CA199 in combination are positively related with poor prognosis. Overexpression of CDX2 reduced expression of MMP-2 and diminished cell proliferation, invasion, and migration, while knockdown CDX2 enhanced MMP-2 expression and increased cell proliferation, invasion, and migration in HCT-116 cells. CDX2 was correlated with expression of EMT markers. Overexpression of CDX2 suppressed the EMT markers indicating that CDX2 suppresses CRC cell viability, invasion, and metastasis through inhibiting EMT. Finally, we found that the expression of CDX2 was negatively associated with Th1 cells, macrophages, Th2 cells, cytotoxic cells, T cells, and T helper cells.ConclusionsThese results indicated CDX2 as prognostic biomarkers involved in immunotherapy response for CRC. CDX2 loss promotes metastasis in CRC through a CDX2-dependent mechanism.

Dataset Information

The Prognostic and Predictive Utility of CDX2 in Colorectal Cancer.

Publications

The Prognostic and Predictive Utility of CDX2 in Colorectal Cancer.

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