Caudal-Type Homeobox Transcription Factor 2 is a Favorable Prognostic Indicator in Stage II and III Gastric Cancer Following Curative Surgery

Yang Xu,1,* Yue Wu,1,* Jianhong Liu,2 Lili Xiao,1 Ying Zhang1 1Department of Gastroenterology, Daqing Oilfield General Hospital, Daqing, Heilongjiang, 163000, People’s Republic of China; 2Department of Breast and Thyroid Surgery, Daqing Oilfield General Hospital, Daqing, Heilongjiang, 163000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ying Zhang, Email [email protected]: The study explored the prognostic value of caudal-type homeobox transcription factor 2 (CDX2) in stage II and III gastric cancer.Methods: This study evaluated the expression level of CDX2 in gastric cancer in a hospital cohort (n=197) using immunohistochemistry. According to a semiquantitative score used to determine CDX2 expression, the cases were divided into a low CDX2 group (116 cases) and a high CDX2 group (81 cases). The RNA-seq expression data from 291 patients with stage II and III gastric cancer from The Cancer Genome Atlas (TCGA) cohort were used to verify the immunohistochemistry results. Based on the median CDX2 expression value, the TCGA patients were divided into a low CDX2 group (145 cases) and a high CDX2 group (146 cases). The relationships among CDX2 expression and clinicopathological features were determined using the Chi-square test. Cox proportional hazards regression models were applied to estimate the independent prognostic factors. The probability of survival was determined using the Kaplan-Meier method and Log rank tests.Results: Based on the Cox multivariate analysis, CDX2 was the independent prognostic factor in the hospital and TCGA cohorts. In the hospital cohort, CDX2 expression was associated with an improved DFS (hazard ratio [HR] = 0.4076, 95% CI, 0.2675– 0.6210, P = 0.0001) and OS (HR = 0.4183, 95% CI, 0.2744– 0.6375, P = 0.0002). In the TCGA cohort, CDX2 expression also was associated with an improved DFS (HR = 0.5948, 95% CI, 0.4153– 0.8521, P = 0.0054) and OS (HR = 0.5976, 95% CI, 0.4172– 0.8561, P = 0.0058). Furthermore, the CDX2 expression level was correlated with an improved DFS (P = 0.0025) and OS (P = 0.0015) using the Kaplan-Meier Plotter database for gastric cancer.Conclusion: CDX2 is a potential prognostic biomarker for stage II and III gastric cancer. In addition, CDX2 positive cancer patients are more likely to have resectable tumors and exhibit better survival rates.Keywords: gastric cancer, CDX2, immunoreactivity, chemotherapy, prognostic marker