In our previous study, we developed a novel computational method and applied it to predict that EL could potentially serve as a highly promising diagnostic urinary marker for gastric cancer. Here, we have further confirmed this prediction on larger sample set, and in addition we discovered that the EL protein is highly specific to gastric cancer.
EL is a new member of the triglyceride lipase gene family, and has high sequence homology with lipoprotein lipase (LPL) (45%), hepatic lipase (HL) (41%) and pancreatic lipase (PL) (21%) [19, 20]. EL has primarily a phospholipase and has some triglyceride lipase activity, which has an important role in plasma high-density lipoproteins metabolism and atherosclerosis development [21–25]. Several studies have shown that LPL plays an important role in carcinogenesis, including colorectal and pancreatic cancers, and lung cancer [26, 27]. However, EL has not been reported to be associated with any cancer except for testicular germ cell tumors, while the mechanism there is unclear .
The discovery that the expression levels of EL is significantly reduced in urine of gastric cancer patients, while showing no difference between the corresponding serum samples as well as tissue samples is very intriguing. One potential reason could be due to the properties of the glomerular filtration system. It is known that plasma proteins were filtered though the glomeruli on the basis of their sizes, charges and structure shape . Small and positively charged molecules were more easily filtered into urine than large and negatively charged proteins. The sequence of EL has a number of positively charged clusters , which may be a reason that it can be filtered out in healthy people’s urine. However, the microenvironment of the cancer cells tend to be more acidic , which may potentially change positively charged clusters of ELs to negative ones, hence preventing the molecules from being filtered into the urine. Certainly, the precise reason is yet to be understood, and warrants further studies.
Urine is an ideal non-invasive source for cancer detection. However, it should be noted that urine has a high degree of variability in protein concentrations throughout a day, which can be influenced by various factors (age, diet, and collection time). For this reason, it is a key to normalize the protein concentration in urine when measuring the expression levels of protein. Therefore, we used the relative EL expression levels with respect to that of the urinary creatinine in each sample to normalize EL expression levels across different urine samples. The results of this study suggest that the loss of urinary EL expression can provide a preliminary indication of gastric cancer during large-scale screening and more direct examinations such as gastroscopy and pathology test on the biopsy sample will be needed for the final diagnosis. Many studies report that diagnostic biomarker may be a useful prognostic and survival indicator for gastric cancers [32–34]. It was not only to predict the prognosis information of cancer patients, but also to provide the treatment strategy for the physician. So we examined the correlation between EL expression levels and the clinicopathological characteristics in gastric cancer. Although EL makes a promising diagnostic marker for gastric cancer, we did not find any strong relationships between the EL expression level and the tumor’s prognostic clinicopathological characteristics such as tumor type, invasion and TNM staging. In addition, because of the short term of study and lack of regular follow up of patients, we can not assess survival rate in this study. The limited existing data showed that EL expression can not be used as a useful prognostic and survival indicators for gastric cancer. The next study, we aimed to investigate the EL protein expression in larger numbers of patients with different tumors and its follow up studies, and to explore the exactly mechanism of EL’s role in the carcinogenesis of gastric cancer.