The Expression Of SPINK1 In The Plasma Of Hepatocellular Carcinoma

Background and ObjectiveLiver cancer is the fifth most common cancer worldwide and the third most common cause of cancer mortality. Hepatocellular carcinoma(HCC), which accounts for 70%~85%, is the predominantly form of liver cancer. The 5-year survival is 0%~10% for the patients who were diagnosed after the onset of symptoms. However, the 5-year survival rate can reach to 70 % if the patient was diagnosed early. So it is very important of the early diagnose of HCC. AFP is most common used biomarker in the clinical for HCC. But it was reported that the AFP-negative patients account for 30%. So the value of AFP is limited for the HCC diagnose and new biomarker are needed.Serpins are a superfamily of proteins. As a member of serpins, SPINK1 draw more attention nowadays. SPINK1 encodes for a 56 amino acid peptide whose function is to inhibit serine proteases. Studies reported that, the SPINK1 gene expression of hepatocellular carcinoma increase significantly compared with normal liver tissue, which may be due to the acute phase response caused by the tumor infiltration. Interleukin 6 and interleukin 1 play important role in the high expression of SPINK1.The aim of the study was to explore the expression of SPINK1 and AFP among the patients of HCC, cirrhosis of the liver, stomach cancer, colon cancer and healthy controls. MaterialThere were 190 participants who were treated in the People's Hospital of Henan Province during October from October 2014 to February 2015 in our study. Blood samples and clinical records including age, gender, and the stage of cancer were collected. There were 70 patients diagnosed with HCC, 30 patients diagnosed with cirrhosis of the liver, 30 patients diagnosed with stomach cancer, and 30 patients diagnosed with colon cancer. Moreover, there were 30 healthy controls who take medical examination in the same hospital. MethodsSample collection 3ml fasting blood were collected from each subjects within EDTA-anticoagulated tube and immediately centrifuged at 3000 r/min for 15 minutes at room temperature. The supernatant was dispensed in the 1.5ml centrifuge tube and then placed in refrigerator of-100 ?.Detection Serum SPINK1, AFP were detected by ELISAStatistical analysis All the analysis were performed with the SPSS software. Continuous variables were compared with t test or ANOVA analysis. Statistical significance was defined as P < 0.05.The sensitivity and specificity of SPINK1 were analyzed based on the ROC curve. ResultsSPINK1 was higher expressed in the HCC compared with cirrhosis of the liver and control group(P<0.01).SPINK1 was higher expressed in the HCC patients with III-IV stage compared with the HCC patients with I-II stage(P<0.05).The sensitivity of SPINK1 and AFP were 77.1% and 51.4%,respectively. And the specificity of SPINK1 and AFP were 67.5% and 96.7%, respectively.Among the 35 AFP-negative patients, there were 28 patients with SPINK1-positive expression.When combined with SPINK1 and AFP for the parallel trial, the sensitivity and specificity were 65.8% and 90%, respectively. While using series joint detection method,the sensitivity and specificity were 98.3% and 37.1%, respectively. Conclusion1. SPINK1 is a potential biomarker for HCC.2. The expression of SPINK1 is associated with the stage of HCC.4. SPINK1 can be used for the diagnosis of AFP-negative patients.5. The accuracy of the diagnosis increases when combined with SPINK1 and AFP.