Relationship between DLEC1 and PBX3 promoter methylation and the risk and prognosis of gastric cancer in peripheral blood leukocytes.

PURPOSE: Aberrant DNA methylation could regulate the expression of tumor suppressor gene DLEC1 and oncogene PBX3 and was related to the occurrence and prognosis of gastric cancer (GC). In this study, the associations between DLEC1 and PBX3 promoter methylation in peripheral blood leukocytes (PBLs) and the risk and prognosis of GC were investigated. METHODS: The methylation status of DLEC1 and PBX3 promoter in PBLs of 368 GC cases and 382 controls was detected by the methylation-sensitive high-resolution melting (MS-HRM) method. Logistic and Cox regression were adopted to analyze the associations of DLEC1 and PBX3 methylation with GC risk and prognosis, respectively. Confounding biases were controlled by propensity score (PS). RESULTS: Compared with negative methylation (Nm), DLEC1-positive methylation (Pm) was associated with increased GC risk in PS (OR 2.083, 95% CI 1.220-3.558, P = 0.007), but PBX3 Pm was not associated with GC risk. In the elderly group (≥ 60 years), DLEC1 Pm was associated with increased GC risk (OR 2.951, 95% CI 1.426-6.104, P = 0.004). The combined effects between DLEC1 methylation and consumption of dairy products, fried food intake and Helicobacter pylori (H. pylori) infection on GC risk were discovered (ORc 3.461, 95% CI 1.847-6.486, P < 0.001, ORc 3.246, 95% CI 1.708-6.170, P < 0.001 and ORc 2.964, 95% CI 1.690-5.197, P < 0.001, respectively). Furthermore, DLEC1 and PBX3 methylation were not associated with GC prognosis. CONCLUSION: DLEC1 methylation in PBLs and the combined effects of gene-environment can influence GC risk.

Association between the methylation of the STAT1 and SOCS3 in peripheral blood and gastric cancer.

BACKGROUND AND AIM: DNA methylation is an important epigenetic modification that can promote the development of various cancers. The STAT1 and SOCS3 have been observed to be hypermethylated in tumor tissues and peripheral blood. This study aimed to explore the relationship between the methylation status of the STAT1 and SOCS3 in peripheral blood and gastric cancer (GC). METHODS: This hospital-based case-control study involved 372 patients with GC and 379 controls. The methylation status of the STAT1 and SOCS3 was semiquantitatively determined using the methylation-sensitive high-resolution melting method. Logistic regression analysis was used to analyze the relationship between the STAT1 and SOCS3 methylation status and GC susceptibility. Moreover, propensity scores were used to control confounding factors. RESULTS: Compared with negative methylation, the positive methylation of SOCS3 significantly increased the risk of GC (ORa  = 1.820, 95% CI: 1.247-2.658, P = 0.002). This trend was also found via stratified analysis, and methylation positivity of the SOCS3 significantly increased the risk of GC in the < 60 years group, in the ≥ 60 years group, and in the positive Helicobacter pylori infection group (ORa  = 1.654, 95% CI: 1.029-2.660, P = 0.038; ORa  = 1.957, 95% CI: 1.136-3.376, P = 0.016; ORa  = 2.084, 95% CI: 1.270-3.422, P = 0.004, respectively). Additionally, no significant association was found between STAT1 methylation and GC risk (ORa  = 0.646, 95% CI: 0.363-1.147, P = 0.135). This study found that the interaction between the methylation status of STAT1 and SOCS3 and environmental factors did not have an impact on GC risk. CONCLUSION: SOCS3 methylation may serve as a new potential biomarker for GC susceptibility.

[Effect of Serum Free Light Chain on Renal Function and Prognosis in Patients with Newly Diagnosed Multiple Myeloma].

OBJECTIVE: To analyze the effect of serum free light chain (sFLC) on renal function and prognosis in patients with newly diagnosed multiple myeloma (MM). METHODS: The clinical data of 70 newly diagnosed MM patients who received sFLC examination in Fujian Medical University Union Hospital were retrospectively analyzed from April 2012 to November 2016. Univariate analysis was used to analyze the risk factors that associated with renal impairment (RI) and prognosis. Logistic regression and Kaplan-Meier analyze were used to analyze the roles of sFLC in RI and the prognosis. RESULTS: Out of the 70 patients, 20 patients had RI at the initial diagnosis. Compared to normal renal function group, RI group had lower level of hemoglobin, elevated levels of serum uric acid, corrected calcium, serum creatinine, serum ß2 microglobulin, and involved sFLC, higher proportion of patients with ISS stage III, involved sFLC≥500 mg/L, hemodialysis (all P＜0.05). Multivariate logistic regression analysis showed that serum uric acid≥430 µmol/L, ISS stage III and a involved sFLC≥500 mg/L were all the independent risk factors for RI in patients with newly diagnosed MM patients (all P＜0.05). Receiver operating characteristic (ROC) curves analysis showed that the involved sFLC was 705.0 mg/L, which was a best cut-off value area under curve (AUC) for prediting RI in patients with MM was 0.727 (P=0.003), sensitivity was 65.0% and specificity was 82.0%). After a median follow-up period of 31 (1-84) months, the median overall survival (OS) of patients with involved sFLC≥500mg/L and involved sFLC＜500 mg/L were 52.0 and 27.0 months, respectively, there was no statistically significant difference (P=0.137). There was also no statistically significant difference in median OS between the high sFLC ratio group (κ/λ＞32 or ＜0.03) and the low sFLC ratio group (0.03≤κ/λ≤32) (27 months vs 40 months, P=0.436). CONCLUSION: The involved sFLC in the RI group is significantly higher than that in the normal renal function group in newly diagnosed MM patients. Serum uric acid≥430 µmol/L, ISS stage III and involved sFLC≥500 mg/L are the independent risk factors for RI. Monitoring sFLC in newly diagnosed MM patients is helpful to the prediction of RI, and the involved sFLC level or sFLC ratio may not affect the prognosis of newly diagnosed MM patients.