FOXO4 and FOXD3 are predictive of prognosis in gastric carcinoma patients.

Abstract

Forkhead box (FOX) transcription factor family plays an important role in cancer growth and metastasis. This study aimed to determine the predictive ability of FOX genes in gastric carcinoma. A total of 360 patients with gastric from The Cancer Genome Atlas (TCGA) cohorts were collected in this study. The expression profile of FOX family were obtained from the TCGA RNAseq database. Clinicopathological characteristics, including age, gender, tumor node metastasis (TNM), tumor grade, and overall survival were collected. Univariate and multivariate Cox proportional hazards model were used to assess the risk factors for survival, and the results were further validated in in-house cohort. In the TCGA cohort, FOXO4 (HR = 0.613, 95%CI 0.452–0.832) and FOXD3 (HR = 1.704, 95%CI 1.212–2.397) were shown independently predictive of overall survival in gastric cancer after Cox proportional hazards analysis. The finding was validated in our in-house cohort, which demonstrated that both FOXO4 and FOXD3 were independent predictors for overall survival (FOXO4 high, HR: 0.445, 95%CI 0.277–0.715, P = 0.001, FOXD3 high, HR: 1.927, 95%CI 1.212–3.063, P = 0.006) and disease free survival (FOXO4 high, HR: 0.628, 95%CI 0.420–0.935, P = 0.022, FOXD3 high, HR: 1.698, 95%CI 1.136–2.540, P = 0.010). Collectively, FOX family paly critical roles in gastric cancer, and FOXO4 and FOXD3 were identified as independent prognostic factors for survival outcomes of gastric cancer. Further functional study is needed to understand more about FOX family in gastric cancer.