Clinical significance of HLA-G in patients with gastric cancer
Objective 
To investigate the clinical significance of CD14+ HLA-G+ monocytes in peripheral blood and the soluble form of HLA-G (sHLA-G) in plasma among patients with gastric cancer (GC). 
 
 
Methods 
Blood samples were collected from 135 patients with gastric cancer (GC group), 150 patients with chronic gastritis (CG group) and 80 healthy controls (HC group). Flow cytometry analysis and ELISA were used to detect the percentages of CD14+ HLA-G+ monocytes in peripheral blood samples, the concentrations of sHLA-G in plasma samples and the levels of alpha fetoprotein (AFP), cacino-embryonic antigen (CEA), CA19-9 and CA125 in serum samples. Mann-Whitney U test was performed to analyze the differences between different groups. The feasibility of using CD14+ HLA-G+ monocytes, sHLA-G, AFP, CEA, CA19-9 and CA125 as potential biomarkers to differentiate patients with GC from those with CG or healthy subjects was assessed by using receiver operating characteristic (ROC) curve analysis. 
 
 
Results 
The median percentages of CD14+ HLA-G+ monocytes in subjects from GC, CG and HC groups were 18.6% (12.1%-26.7%), 7.3% (4.2%-11.0%) and 4.6% (3.6%-6.3%), respectively. The percentages of CD14+ HLA-G+ monocytes in the peripheral blood of patients with GC were significantly higher than those in patients with CG and healthy subjects (P<0.001). The concentrations of sHLA-G in plasma samples collected from patients with GC [(100.6±61.3) U/ml) were significantly higher than those in patients with CG [(59.5±19.9) U/ml) and healthy subjects [(45.8±23.3) U/ml] (P<0.001). ROC curve analysis showed that in terms of GC diagnosis, the area under ROC curve (AUC), cutoff value, sensitivity and specificity for CD14+ HLA-G+ monocytes and sHLA-G in plasma were 0.893 and 0.720, 12% and 85 U/mL, 75.8% and 50.5%, 86.7% and 95.9% (P<0.001), respectively, which indicated that CD14+ HLA-G+ monocytes and sHLA-G were better than AFP, CEA, CA19-9 and CA125 in differentiating GC from CG and HC. Moreover, the multivariate logistic regression analysis revealed that the CD14+ HLA-G+ monocytes, sHLA-G in plasma as well as CA19-9 and CA125 in serum were positively correlated with the risk of GC after excluding the differences caused by age and gender factors. 
 
 
Conclusion 
The levels of CD14+ HLA-G+ monocytes in peripheral blood and sHLA-G in plasma increased dramatically in patients with gastric cancer, which suggested that CD14+ HLA-G+ monocytes and sHLA-G might be risk factors for GC and could be used as potential biomarkers for the diagnosis of GC. 
 
 
Key words: 
Gastric cancer; CD14+ HLA-G+ monocytes; sHLA-G