ABSTRACT
OBJECTIVE: The myeloid differentiation factor-88 (MyD88) plays a key role in mediating the innate immune signal transduction of toll-like receptor (TLR) and interleukin-1 (IL-1) family members, and it also participates in the regulation of tumorigenesis in various cancer models Our study sought to determine whether there is any correlation with MyD88 and the development of gastric cancer and, if such a correlation exists, to find out whether it can be used to improve the prognosis of gastric cancer patients. PATIENTS AND METHODS: The expression of MyD88 in 108 cases of gastric cancer specimens, 15 cases of adenoma, and 15 cases of normal mucosa was detected by immunohistochemistry, and the correlations of the MyD88 expression with clinicopathologic changes (including disease-free survival [DFS] and overall survival [OS] were analyzed. The level of MyD88 was detected in well-differentiated MGC-803 and poorly-differentiated BGC-823 cell lines by qPCR and western blot. The expression of MyD88 was then measured by western blot after the treatment of an MyD88 overexpression vector or MyD88 inhibitor. Cell proliferation was determined by overexpression or suppression of MyD88. RESULTS: In clinical cases, MyD88 was highly expressed in 23% of patients with gastric cancer as compared to those in normal mucosa and adenoma. There was a significant correlation of MyD88 overexpression with gastric metastasis (P<0.01). The overexpression of MyD88 significantly promoted the proliferation of MGC-803 and BGC-823 cell lines in gastric cancer. According to the single factor analysis, a high expression of MyD88 was strongly associated with poor DFS and OS (P<0.01), and MyD88 was an independent prognostic factor of OS. CONCLUSION: This study demonstrates that a high expression of MyD88 is associated with the gastric cancer patients with liver metastasis, and facilitates the proliferation of gastric cancer cells. MyD88 is an independent predictive factor for the poor prognosis of gastric cancer patients, which provides a potential tool for future clinical diagnosis.
ABSTRACT
BACKGROUND AND PURPOSE: High sensitivity C-reaction protein (hsCRP) has been used as a significant predictive factor of cardiovascular events in patients with non-insulin dependent diabetes mellitus (NIDDM). However, existing reports in regards to the significance of hsCRP in predicting the progression of hepatic complications in NIDDM patients are too sparse to deliver clear results. This study is aimed at investigating the prognostic value of hsCRP in NIDDM patients with non-alcoholic fatty liver disease (NAFLD). METHODS: 1128 NIDDM patients with a definite diagnosis of NAFLD were enrolled and followed for one year. The baseline body mass index (BMI), waist-hip circumference ratio (WHR), serum aspartate aminotransferase (AST), presence of hypertension, alanine aminotransferase (ALT), serum hsCRP, total cholesterol (Tch), fasting blood glucose (FBG), triglycerine (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and hepatitis B surface antigen (HBsAg) were recorded to analyze the significance of hsCRP in predicting the short-term progression from NAFLD to non-alcoholic steatohepatitis (NASH). RESULTS: One year after baseline, 32% of the NAFLD patients suffered progression to NASH and the percentages of NASH were respectively 8.2%, 12.5%, 33.8% and 72.6% in 4 groups with quartered baseline serum level of hsCRP; there was significant difference among the 4 groups in percentage of NASH (P<0.001). With sex, age, WHR, BMI, hypertension, TG, TCH, HDL-C, LDL-C, FBG and HBsAg included, the calibrated regression model gave the OR values of 1.000, 1.669, 6.635 and 32.131 in in 4 quartered baseline serum levels of hsCRP. CONCLUSION: High serum level of hsCRP is an independent risk factor of short-term progression to NASH in patients with NIDDM and NAFLD. Those NIDDM patients with NAFLD that present with high serum level of hsCRP should be subjected to regular monitoring, lifestyle intervention and medication.
