Ben Y Zhang1, Jeremy C Jones1, Andrew M Briggler2, Joleen M Hubbard1, Benjamin R Kipp3, Daniel J Sargent4, Jesse G Dixon4, Axel Grothey5. 1. Department of Oncology, Mayo Clinic, Rochester, MN. 2. Department of Medicine, Mayo Clinic, Rochester, MN. 3. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN. 4. Department of Health Sciences Research, Mayo Clinic, Rochester, MN. 5. Department of Oncology, Mayo Clinic, Rochester, MN. Electronic address: Grothey.axel@mayo.edu.
Abstract
BACKGROUND: Although the lack of CDX2 expression has recently been proposed as a potential biomarker for a high risk of relapse in patients with stage II and III colon cancer after complete surgical resection, its prognostic role in metastatic colorectal cancer (CRC) remains unclear and warrants investigation. MATERIALS AND METHODS: We identified 145 patients treated at our institution from 2006 to 2016, including 66 patients with CDX2-negative metastatic CRC and a comparison cohort of 79 patients with CDX2-positive metastatic CRC. Overall survival (OS) and progression-free survival (PFS) for first-line systemic therapy were estimated using the Kaplan-Meier method. The associations of CDX2 expression with survival were evaluated using Cox proportional hazards regression models. RESULTS: The prevalence of absent CDX2 expression in our cohort was 5.6%. Patients with CDX2-negative metastatic CRC were significantly more likely to be female, and to have right-sided primary tumors, poorly differentiated histologic features, and distant lymph node metastasis. The median OS for patients with CDX2-negative and -positive metastatic CRC was 8 and 39 months, respectively (hazard ratio [HR], 4.04; 95% confidence interval [CI], 2.49-6.54; P < .0001). After adjusting for covariates in a multivariate model, the association of a lack of CDX2 expression and OS remained statistically significant (HR, 4.52; 95% CI, 2.50-8.17; P < .0001). In addition, the median PFS (3 vs. 10 months; HR, 2.23; 95% CI, 1.52-3.27; P < .0001) for first-line chemotherapy was significantly decreased in patients with CDX2-negative metastatic CRC. CONCLUSION: The results of the present study show that a lack of CDX2 expression in metastatic CRC is an adverse prognostic feature and a potential negative predictor of the response to chemotherapy.
BACKGROUND: Although the lack of CDX2 expression has recently been proposed as a potential biomarker for a high risk of relapse in patients with stage II and III colon cancer after complete surgical resection, its prognostic role in metastatic colorectal cancer (CRC) remains unclear and warrants investigation. MATERIALS AND METHODS: We identified 145 patients treated at our institution from 2006 to 2016, including 66 patients with CDX2-negative metastatic CRC and a comparison cohort of 79 patients with CDX2-positive metastatic CRC. Overall survival (OS) and progression-free survival (PFS) for first-line systemic therapy were estimated using the Kaplan-Meier method. The associations of CDX2 expression with survival were evaluated using Cox proportional hazards regression models. RESULTS: The prevalence of absent CDX2 expression in our cohort was 5.6%. Patients with CDX2-negative metastatic CRC were significantly more likely to be female, and to have right-sided primary tumors, poorly differentiated histologic features, and distant lymph node metastasis. The median OS for patients with CDX2-negative and -positive metastatic CRC was 8 and 39 months, respectively (hazard ratio [HR], 4.04; 95% confidence interval [CI], 2.49-6.54; P < .0001). After adjusting for covariates in a multivariate model, the association of a lack of CDX2 expression and OS remained statistically significant (HR, 4.52; 95% CI, 2.50-8.17; P < .0001). In addition, the median PFS (3 vs. 10 months; HR, 2.23; 95% CI, 1.52-3.27; P < .0001) for first-line chemotherapy was significantly decreased in patients with CDX2-negative metastatic CRC. CONCLUSION: The results of the present study show that a lack of CDX2 expression in metastatic CRC is an adverse prognostic feature and a potential negative predictor of the response to chemotherapy.
Authors: Luai R Zarour; Sudarshan Anand; Kevin G Billingsley; William H Bisson; Andrea Cercek; Michael F Clarke; Lisa M Coussens; Charles E Gast; Cristina B Geltzeiler; Lissi Hansen; Katherine A Kelley; Charles D Lopez; Shushan R Rana; Rebecca Ruhl; V Liana Tsikitis; Gina M Vaccaro; Melissa H Wong; Skye C Mayo Journal: Cell Mol Gastroenterol Hepatol Date: 2017-01-20
Authors: Janina Graule; Kristin Uth; Elia Fischer; Irene Centeno; José A Galván; Micha Eichmann; Tilman T Rau; Rupert Langer; Heather Dawson; Ulrich Nitsche; Peter Traeger; Martin D Berger; Beat Schnüriger; Marion Hädrich; Peter Studer; Daniel Inderbitzin; Alessandro Lugli; Mario P Tschan; Inti Zlobec Journal: Clin Epigenetics Date: 2018-09-26 Impact factor: 6.551