Zi-Jun Xu1, Chun-Yan Tang2, Jing-Dong Zhou3, Ji-Chun Ma1, Xiang-Mei Wen1, Zhao-Qun Deng4, Jia-Yan Leng3, Zhi-Yuan Qiu5, Jun Qian6, Jiang Lin7. 1. Laboratory Center, Affiliated People's Hospital of Jiangsu University, Zhenjiang 212002, Jiangsu, PR China; Zhenjiang Clinical Research Center of Hematology, Zhenjiang 212002, Jiangsu, P.R. China; The Key Lab of Precision Diagnosis and Treatment in Hematologic Malignancies of Zhenjiang City, Zhenjiang 212002, Jiangsu, P.R. China. 2. Department of Nephropathy and Hematology, The First People's Hospital of Aksu Prefecture of Xinjiang, Aksu 843000, Xinjiang, P.R. China. 3. Zhenjiang Clinical Research Center of Hematology, Zhenjiang 212002, Jiangsu, P.R. China; Department of Hematology, Affiliated People's Hospital of Jiangsu University, Zhenjiang 212002, Jiangsu, P.R. China. 4. Laboratory Center, Affiliated People's Hospital of Jiangsu University, Zhenjiang 212002, Jiangsu, PR China; Zhenjiang Clinical Research Center of Hematology, Zhenjiang 212002, Jiangsu, P.R. China; The Key Lab of Precision Diagnosis and Treatment in Hematologic Malignancies of Zhenjiang City, Zhenjiang 212002, Jiangsu, P.R. China. Electronic address: zqdeng2002@163.com. 5. Department of Oncology, Affiliated People's Hospital of Jiangsu University, Zhenjiang 212002, Jiangsu, P.R. China. 6. Zhenjiang Clinical Research Center of Hematology, Zhenjiang 212002, Jiangsu, P.R. China; Department of Hematology, Affiliated People's Hospital of Jiangsu University, Zhenjiang 212002, Jiangsu, P.R. China. Electronic address: qianjun0007@hotmail.com. 7. Laboratory Center, Affiliated People's Hospital of Jiangsu University, Zhenjiang 212002, Jiangsu, PR China; Zhenjiang Clinical Research Center of Hematology, Zhenjiang 212002, Jiangsu, P.R. China; The Key Lab of Precision Diagnosis and Treatment in Hematologic Malignancies of Zhenjiang City, Zhenjiang 212002, Jiangsu, P.R. China. Electronic address: linjiangmail@sina.com.
Abstract
OBJECTIVE: SOX7 downregulation caused by its promoter methylation was associated with poor survival in several types of human solid tumors. However, the pattern of SOX7 methylation and its clinical significance are less studied in hematological malignancies. Herein, we evaluated the methylation pattern of SOX7 in myelodysplastic syndrome (MDS) and determined its clinical implication in patients with MDS. METHODS: SOX7 methylation was determined by real-time quantitative methylation-specific PCR (RQ-MSP) in 99 MDS patients. Bisulfite sequencing PCR was applied to confirm the results of RQ-MSP. RESULTS: SOX7 methylation was detected in 55.6% of 99 patients but not in healthy donors. No correlation was found between SOX7 methylation and clinical parameters including patient age, gender, white blood cell count, hemoglobin, and platelet count. However, patients with SOX7 methylation harbored more U2AF1 mutation than patients without SOX7 methylation (P = 0.015). Kaplan-Meier curves indicated that the patients with SOX7 methylation presented reduced overall survival (OS) (P = 0.034). Furthermore, subgroup analysis indicated that SOX7 methylation was associated with poor OS in male patients (P = 0.034) and in patients older than 60 years (P = 0.019). According to the multivariate analysis, SOX7 methylation remained as an independent prognosis factor in MDS patients both as dichotomous (HR = 2.14, P = 0.041) and as continuous (HR = 1.55, P = 0.042) variable. Importantly, SOX7 methylation was significantly increased during progression from MDS to secondary acute myeloid leukemia (sAML). CONCLUSIONS: Our findings demonstrated that SOX7 methylation conferred adverse prognosis in MDS patients and was associated with leukemia progression.
OBJECTIVE:SOX7 downregulation caused by its promoter methylation was associated with poor survival in several types of humansolid tumors. However, the pattern of SOX7 methylation and its clinical significance are less studied in hematological malignancies. Herein, we evaluated the methylation pattern of SOX7 in myelodysplastic syndrome (MDS) and determined its clinical implication in patients with MDS. METHODS:SOX7 methylation was determined by real-time quantitative methylation-specific PCR (RQ-MSP) in 99 MDSpatients. Bisulfite sequencing PCR was applied to confirm the results of RQ-MSP. RESULTS:SOX7 methylation was detected in 55.6% of 99 patients but not in healthy donors. No correlation was found between SOX7 methylation and clinical parameters including patient age, gender, white blood cell count, hemoglobin, and platelet count. However, patients with SOX7 methylation harbored more U2AF1 mutation than patients without SOX7 methylation (P = 0.015). Kaplan-Meier curves indicated that the patients with SOX7 methylation presented reduced overall survival (OS) (P = 0.034). Furthermore, subgroup analysis indicated that SOX7 methylation was associated with poor OS in male patients (P = 0.034) and in patients older than 60 years (P = 0.019). According to the multivariate analysis, SOX7 methylation remained as an independent prognosis factor in MDSpatients both as dichotomous (HR = 2.14, P = 0.041) and as continuous (HR = 1.55, P = 0.042) variable. Importantly, SOX7 methylation was significantly increased during progression from MDS to secondary acute myeloid leukemia (sAML). CONCLUSIONS: Our findings demonstrated that SOX7 methylation conferred adverse prognosis in MDSpatients and was associated with leukemia progression.