Pancreatic cancer (PC) is a devastating disease that has a poor prognosis and a total 5-year survival rate of around 5%. The poor prognosis of PC is due in part to a lack of suitable biomarkers that can allow early diagnosis. The lysophospholipase autotaxin (ATX) and its product lysophosphatidic acid (LPA) play an essential role in disease progression in PC patients and are associated with increased morbidity in several types of cancer. In this study, we evaluated both the potential role of serum LPA and ATX as diagnostic markers in PC and their prognostic value for PC either alone or in combination with CA19-9.
Serum samples were gathered from 328 individuals, who were divided into three groups: Group A had 114 PC patients, Groups B and Group C served as cohort control groups and comprised 120 healthy volunteers (HVs) and 94 patients with benign pancreatic diseases (BPDs), respectively. All the patients were consecutively admitted to the General Hospital of Northern Theater Command, Shenyang, China between January 2013 and May 2019. The research protocol was adopted through the Ethics Committee of the General Hospital of Northern Theater Command, and the number was K(2012)49. Informed written consents were obtained for all participants.
"High sugar diet" was defined according to the standard of the American Heart Association (AHA) [19]. For men, Eating more than 37.5 g or 9 teaspoons of sugar a day is considered a high sugar diet. For women, the standard was changed to 25 g or 6 teaspoons of sugar per day. The "Alcohol consumption" was defined according to the standard of the National Institute on Alcohol Abuse and Alcoholism (NIAAA) [20]. The excessive drinking is 14 × 8 g pure alcohol / day or 14 × 20 g pure alcohol / week for men, and 14 × 4 g pure alcohol / day or 14 × 8 g pure alcohol / week for women. In this study, High sugar diet and alcohol consumption were ascertained at all visits by means of an interviewer-administered dietary questionnaire. In calculating the amount of sugar or alcohol consumed (in grams per day or per week), people were judged whether they currently with the high sugar diet or excessive drinking.
A total of 10 mL of venous blood was collected from each participant into sterile vacutainers. The samples were centrifuged at 3,500 g for 10 min and serum aliquots were stored at -80 ˚C. The samples were thawed prior to measurement of ATX, LPA and CA19-9 blood levels. Blood biochemical parameters including total bilirubin, albumin, alanine alkaline phosphatase, aspartate aminotransferase, γ-glutamyl transferase, transaminase, glucose, creatinine, prothrombin time, D-dimer and activated partial prothrombin time were measured using a Siemens ADVIA1800 chemistry analyzer.
Serum levels of LPA, ATX and CA19-9 were assayed by ELISA (Cloud-Clone Corp., TX, USA) and estimated by interpolation from a standard curve produced using known amounts of each protein. The samples were serially diluted with PBS and assessed again to ensure that the concentrations were within measurable ranges. The investigators were blinded to sample origin and all tests were executed in triplicate following the manufacturer’s instructions.
Serum levels of ATX, LPA and CA19-9 in PC patients were substantially higher than that for BPD patients or HVs (p < 0.001). The sensitivity of LPA in early phase PC was 91.74% and the specificity of ATX was 80%. The levels of ATX, LPA and CA19-9 were all substantially higher for early stage PC patients compared to levels in serum from BPD patients and HVs. The diagnostic efficacy of CA19-9 for PC was significantly enhanced by the addition of ATX and LPA (p = 0.0012).
Measurement of LPA and ATX levels together with CA19-9 levels can be used for early detection of PC and diagnosis of PC in general. Recently scientists from General Hospital of Northern Theater Command has published their study in BMC Gastroenterology.
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