Diagnostic and Prognostic Value of DACH1 Methylation in the Sensitivity of Esophageal Cancer to Radiotherapy

Abstract

To detect the methylation status of the cell fate determinant (DACH1) gene in esophageal cancer tissues and to explore the predictive value of methylation of DACH1 on the sensitivity to radiotherapy for esophageal cancer. Cancer tissues, corresponding paracancerous tissues, and 30 specimens of normal esophageal mucosal tissues from 70 patients admitted to the hospital after radical esophageal cancer radiotherapy from January 2016 to April 2017 were collected. The methylation status of DACH1 was detected by a methylation-specific polymerase chain reaction (MSP). The 70 esophageal cancer patients were divided into radiotherapy-sensitive and radiotherapy-insensitive groups according to the efficacy of radiotherapy, and the methylation status of DACH1 was compared between the two groups. The χ2 test was used to analyze the relationship between the methylation status of DACH1 and the clinicopathological characteristics of esophageal cancer patients. The Kaplan–Meier survival curve was used to analyze the relationship between the methylation status of DACH1 and radiotherapy sensitivity and survival of esophageal cancer patients, and the Cox proportional risk model was used to analyze the independent influencing factors affecting the radiotherapy sensitivity of esophageal cancer patients. The methylation rate of DACH1 in esophageal cancer tissues was higher than that in paracancerous tissues and normal tissues, and the differences were statistically significant ( $P<0.05$ ). 70 patients with esophageal cancer completed radiotherapy, including 46 patients with radiotherapy sensitivity and 24 patients with radiotherapy insensitivity. The DACH1 methylation rate of esophageal cancer patients in the radiotherapy-sensitive group was lower than that in the radiotherapy-insensitive group, and the difference was statistically significant ( $P<0.05$ ). The DACH1 methylation rate of esophageal cancer patients with TNM stage (III-IV), tumor differentiation degree (hypofractionation), and lymph node metastasis was higher, and the difference was statistically significant ( $P<0.05$ ). The Kaplan–Meier curve showed that the median survival time of patients with DACH1 methylation before radiotherapy was 23 months, which was shorter than that of patients with DACH1 unmethylation before radiotherapy (36 months), and the difference between the survival curves of the two groups was statistically significant (χ2 = 7.425, $P<0.05$ ); the median survival time of patients in the radiotherapy-sensitive group was 39 months, which was longer than that of patients in the radiotherapy-insensitive group (25 months), and the difference between the two groups was statistically significant ( $P<0.05$ ). The median survival time of patients in the radiotherapy-sensitive group was 39 months, which was longer than that of patients in the radiotherapy-insensitive group (25 months), and the difference in survival curves between the two groups was statistically significant (χ2 = 7.011, $P<0.05$ ). The results of the multifactorial Cox regression model showed that TNM stage (stage III-IV) (HR = 1.961, 95% CI: 1.125–2.768), tumor hypofractionation (HR = 1.453, 95% CI: 1.034–2.857), presence of lymph node metastasis (HR = 1.499, 95% CI: 1.025–2.851), and DACH1 methylation (HR = 1.718, 95% CI: 1.067–2.596) may increase the risk of insensitivity to radiotherapy in patients with esophageal cancer ( $P<0.05$ ). The rate of DACH1 methylation in esophageal cancer tissues was increased, and the methylation status of DACH1 was related to radiotherapy sensitivity and survival of esophageal cancer patients, which is expected to be a new target for diagnosis and treatment of esophageal cancer patients.