Association of CDX2 Expression With Survival in Early Colorectal Cancer: A Systematic Review and Meta-analysis

Tomasello, Gianluca; Barni, Sandro; Turati, Luca; Ghidini, Michele; Pezzica, E; Passalacqua, Rodolfo; Petrelli, Fausto

doi:10.1016/j.clcc.2018.02.001

Cited by 33 publications

(33 citation statements)

References 30 publications

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“…Such varied biomarkers were found because of the limited number of tumor specimens and the range of genomic backgrounds of patients. One of these biomarkers, CDX2, is a homeobox gene encoding transcriptional factors for intestinal organogenesis and has been confirmed to be a strong prognostic factor in stage II and III CRC . Additionally, peroxisome proliferator–activated receptor gamma coactivator 1 alpha (PGC‐1α) can be used as a biomarker of physical activity–protective effect on colorectal cancer .…”

Section: Discussionmentioning

confidence: 99%

Candidate genes involved in metastasis of colon cancer identified by integrated analysis

et al. 2019

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Colon cancer is one of the most malignant cancers worldwide. Nearly 20% of all colon cancer patients are diagnosed at stage IV (metastasis). However, further study of colon cancer is difficult due to a lack of understanding of its pathogenesis. In this study, we acquired high–throughput sequence data from TCGA datasets and performed integrated bioinformatic analysis including differential gene expression analysis, gene ontology and KEGG pathways analysis, protein–protein analysis, survival analysis, and multivariate Cox proportional hazards regression analysis in order to identify a panel of key candidate genes involved in the metastasis of colon cancer. We then constructed a prognostic signature based on the expression of REG1B, TGM6, NTF4, PNMA5, and HOXC13 which could provide significant prognostic value for colon cancer.

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Section: Discussionmentioning

confidence: 99%

Candidate genes involved in metastasis of colon cancer identified by integrated analysis

et al. 2019

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“…Caudle type homeobox 2 ( CDX2 ) expression analysis by immunohistochemistry (IHC) has been shown to be a prognostic factor in stage II and III CRC according to Tomasello et al [55]. Low CDX2 expression was been shown to be a negative prognostic factor distinguishing between high and low mortality/disease progression with a hazard ratio (HR) of 0.5 [95% confidence interval (CI) = 0.38–0.66, P < 0.001] in a large 14-study meta-analysis and has appeal based on its accessibility and low cost.…”

Section: Tools Available For Predicting Chemotherapy Benefitsmentioning

confidence: 99%

Challenges and solutions in patient treatment strategies for stage II colon cancer

Fotheringham¹,

Mozolowski²,

Murray

et al. 2019

Gastroenterology Report

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Colorectal cancer remains one of the most common cancers worldwide and, despite improvements in treatment options for late-stage metastatic cancer, there are still questions surrounding how best to treat early-stage disease patients. Some recent advances have been made in the staging of cancer and improving the risk assessment of strategies for patient treatment. A number of high-risk features have been proposed that may help to stratify stage II cancer patients into groups that will truly benefit from adjuvant chemotherapy. Diagnostic tests are becoming available to measure these biomarkers, utilizing both currently available and novel technologies. This review will describe the challenges in treatment decisions for early-stage colon cancer and how personalized medicine can assist clinicians in making the best treatment choices for patients with stage II colon cancer in particular.

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“…Immunohistochemistry (IHC) analysis for CDX2 is implemented in the clinical diagnostics as a biomarker for intestinal differentiation in tumors of unknown origin. It is deregulated in a subset of patients with CRC, and downregulation has been associated with poor prognosis (6)(7)(8)(9)(10)(11)(12)(13). Loss of CDX2 expression has also been associated with other poor prognostic features such as advanced stages, poor differentiation, BRAF mutation (BRAFmut), and microsatellite instability (MSI) (12,14,15).…”

Section: Introductionmentioning

confidence: 99%

CDX2: A Prognostic Marker in Metastatic Colorectal Cancer Defining a Better BRAF Mutated and a Worse KRAS Mutated Subgroup

et al. 2020

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Background: Survival of metastatic colorectal cancer (mCRC) patients has improved, but mainly for trial patients. New predictive and prognostic biomarkers validated in the general mCRC population are needed. Caudal-type homeobox 2 (CDX2) is an intestine-specific transcription factor with potential prognostic and predictive effect, but the importance in mCRC has not been fully investigated. Methods: Immunohistochemistry analysis of CDX2 was performed in a Scandinavian population-based cohort of mCRC (n = 796). Frequency, clinical and tumor characteristics, response rate, progression-free survival, and overall survival (OS) were estimated. Results: Loss of CDX2 expression was found in 87 (19%) of 452 stained cases, in 53% if BRAF mutated (BRAFmut) and in 9% if KRAS mutated (KRASmut). CDX2 loss was associated with microsatellite instability, BRAFmut, and poor differentiation and inversely associated with KRASmut. Patients with CDX2 loss received less first-line (53 vs. 64%, p = 0.050) and second-line (23 vs. 39%, p = 0.006) chemotherapy and secondary surgery (1 vs. 9%, p = 0.019). Median progression-free survival and OS for patients given first-line combination chemotherapy was 4 and 10 months if CDX2 loss vs. 9 and 24 months if CDX2 expressed (p = 0.001, p < 0.001). Immediate progression on first-line combination chemotherapy was seen in 35% of patients with CDX2 loss vs. 10% if CDX2 expressed (p = 0.003). Median OS in patients with BRAFmut or KRASmut and CDX2 expressed in tumor (both 21 months) was comparable to wild-type patients (27 months). However, if CDX2 loss, median OS was only 8 and 11 months in BRAFmut and KRASmut cases, respectively, and 10 months in double wild-type patients. In multivariate analysis, CDX2 loss (hazard ratio: 1.50, p = 0.027) and BRAFmut (hazard ratio: 1.62, p = 0.012) were independent poor prognostic markers for OS. Aasebø et al. CDX2 in Metastatic Colorectal Cancer Conclusion: In a population-based cohort of mCRC patients, CDX2 loss is an independent poor prognostic marker. Expression of CDX2 defines a new subgroup of BRAFmut cases with a much better prognosis. Loss of CDX2 defines a small group of KRASmut cases with a worse prognosis. Patients with CDX2 loss receive less palliative chemotherapy with less benefit and rarely reach secondary surgery.

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Association of CDX2 Expression With Survival in Early Colorectal Cancer: A Systematic Review and Meta-analysis

Cited by 33 publications

References 30 publications

Candidate genes involved in metastasis of colon cancer identified by integrated analysis

Candidate genes involved in metastasis of colon cancer identified by integrated analysis

Challenges and solutions in patient treatment strategies for stage II colon cancer

CDX2: A Prognostic Marker in Metastatic Colorectal Cancer Defining a Better BRAF Mutated and a Worse KRAS Mutated Subgroup

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