Serum Mac-2 binding protein is a novel biomarker for chronic pancreatitis

AIM: To determine the efficacy of Mac-2 binding protein(Mac-2bp) for diagnosis of chronic pancreatitis.METHODS: Fifty-nine healthy volunteers(HV), 162 patients with chronic pancreatitis(CP), and 94 patients with pancreatic ductal adenocarcinoma(PDAC) were enrolled in this study. We measured serum Mac-2bp using our developed enzyme-linked immunosorbent assay kit. Additional biochemical variables were measured using an automated analyzer(including aminotransferase, alanine aminotransferase, γ-glutamyltransferase, alkaline phosphatase, triglyceride, C-reactive protein, and amylase levels) or chemiluminescent enzyme immunoassay(carbohydrate antigen 19-9 and carcinoembryonic antigen). The ability of Mac-2bp to predict CP diagnosis accurately was assessed using receiver operating characteristic(ROC) analyses.RESULTS: Serum Mac-2bp levels were significantly increased in CP patients compared to HV(P 0.0001) and PDAC patients(P 0.0001). Area under the ROC curve values of Mac-2bp for the discrimination of CP from HV and PDAC were 0.727 and 0.784, respectively. Multivariate analyses demonstrated that serum Mac-2bp levels were independent determinants for CP diagnosis from HV and PDAC patients. Immunohistological staining showed that Mac-2bp was expressed faintly in the pancreas tissues of both CP and PDAC patients. Serum aspartate aminotransferase, alanine aminotransferase, γ-glutamyltransferase, alkaline phosphatase, and triglyceride levels were significantly higher in patients with CP or PDAC. Serum Mac-2bp levels were highly correlated with protein levels of alanine aminotransferase, γ-glutamyltransferase, and C-reactive protein, but not amylase, suggesting that the damaged liver produces Mac-2bp. CONCLUSION: Measurement of serum Mac-2bp may be a novel and useful biomarker for CP diagnosis as well as liver fibrosis in the general population.     

Serum Wisteria floribunda agglutinin‐positive Mac‐2‐binding protein for patients with chronic hepatitis B and C: a comparative study

We compared Wisteria floribunda agglutinin‐positive Mac‐2‐binding protein (WFA⁺‐M2BP) levels between patients with chronic hepatitis B (n=249) and chronic hepatitis C (n=386) based on the degree of liver fibrosis. We examined WFA⁺‐M2BP levels in patients with F4 (cirrhosis), F3 or more (advanced fibrosis) and F2 or more (significant fibrosis) in the two groups. We further examined the relationship between five fibrosis markers and the degree of fibrosis. The WFA⁺‐M2BP values ranged from 0.25 cut‐off index (COI) to 12.9 COI in patients with hepatitis B and 0.34–20.0 COI in patients with hepatitis C (P<.0001). The median WFA⁺‐M2BP values in F4 in the two groups were 2.83 COI in patients with hepatitis B and 5.03 COI in patients with hepatitis C (P=.0046). The median WFA⁺‐M2BP values in F3 or more in the two groups were 1.79 COI in patients with hepatitis B and 3.79 COI in patients with hepatitis C (P<.0001). The median WFA⁺‐M2BP values in F2 or more in the two groups were 1.49 COI in the hepatitis B cohort and 3.19 COI in the hepatitis C group (P<.0001). Among five liver fibrosis markers, WFA⁺‐M2BP had the highest correlation coefficient (r_s=.629) in terms of correlation with the degree of fibrosis in the patients with hepatitis C and had the second highest r_s value (.415) in the hepatitis B group. Although WFA⁺‐M2BP could be a useful indicator of liver fibrosis, WFA⁺‐M2BP levels in the two groups significantly differed even in the same degree of fibrosis. Individual cut‐off values in each aetiology for the degree of fibrosis should be determined.     

Serum Wisteria floribunda agglutinin-positive Mac-2-binding protein expression predicts disease severity in chronic hepatitis C patients

Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA⁺-M2BP) has recently been developed as a promising liver fibrosis glyco biomarker. We assessed its efficacy in evaluating liver disease severity in chronic hepatitis C (CHC) in Taiwan. The association between WFA⁺-M2BP and histological features was evaluated among those CHC patients underwent liver biopsy. We also aimed to clarify the factors determining the performance of WFA⁺-M2BP in CHC. A total of 229 CHC patients were consecutively recruited. The mean value of WFA⁺-M2BP in patients from F0 to F4 was 1.68, 2.23, 3.45, 3.48, 3.77 respectively (linear trend P = 0.008). Linear regression analysis revealed that alanine aminotransferase (odds ratio [OR]: 0.03, 95% confidence intervals [CI]: 0.02–0.05, P < 0.001), AST (OR: ?0.1, 95% CI: ?0.02 to ?0.01, P < 0.001), and liver fibrosis (OR: 0.30, 95% CI: 0.01–0.59, P = 0.043) were the independent factors correlated to serum WFA⁺-M2BP level. The optimal cutoff values of WFA⁺-M2BP for fibrosis stages F1, F2, F3, and F4 were 1.42, 1.61, 1.42, and 2.67, respectively. Multivariate analysis revealed that the platelet count (OR/CI: ?0.009/0.986–0.996, P = <0.001), r-glutamyl transferase (OR/CI: 0.007/1.000–1.013, P = 0.036), and WFA⁺-M2BP (OR/CI: 0.187/1.057–1.374, P = 0.005). We concluded that WFA⁺-M2BP is a competent noninvasive marker for liver fibrosis assessment in CHC patients.     

Lumican蛋白在胰腺导管腺癌间质中的表达及其与Ki-67、VEGF及突变型P53表达的相关性

目的:观察细胞外基质蛋白Lumican在胰腺导管腺癌(pancreatic ductal adenocarcinoma,PDA)中表达特征,分析Lumican与Ki-67、VEGF、突变型P53等肿瘤恶性表型相关分子的关联.方法:采用免疫组织化学染色(IHC)和逆转录-聚合酶链式反应(RT-PCR)检测PDA原发灶及对应癌旁胰腺组织中Lumican表达.IHC检测PDA原发灶Ki-67、VEGF及突变型P53表达.用SPSS软件行统计学分析.结果:PDA原发灶中,Lumican表达在mRNA及蛋白质水平均明显高于癌旁胰腺组织.就该蛋白在癌灶中的分布特性而言,Lumican蛋白主要定位于癌间质,阳性表达率为83.0%(83/100).低分化PDA中,癌间质过表达Lumican与TNM分期相关(x2=6.446,P<0.05),与年龄、性别、淋巴结转移、远处转移等无明显相关.高中分化PDA中,癌间质过表达Lumican与临床病理特征无关,而与Ki-67(r=-0.28,P=0.017)、VEGF(r=-0.264,P=0.025)及突变型P53(r=-0.253,P=0.032)表达呈明显负相关.结论:Lumican在PDA原发灶中表达高于癌旁胰腺组织,主要分布于癌间质.Lumican在癌间质过表达与低分化PDA的TNM分期相关,与高、中分化PDA的Ki-67、VEGF及突变型P53表达呈负相关.     

Expression of fibroblast activation protein in human pancreatic adenocarcinoma and its clinicopathological significance

AIM: To examine fibroblast activation protein (FAP) expression in pancreatic ductal adenocarcinoma (PDAC) and to analyze its relationship with the clinicopathology of PDAC.METHODS: FAP expression was examined in 134 PDAC specimens by immunohistochemistry, and in four pancreatic cancer cell lines (SW1990, Miapaca-2, AsPC-1 and BxPC-3) by Western blotting assay. We also analyzed the association between FAP expression in PDAC cells and the clinicopathology of PDAC patients.RESULTS: The results showed that the FAP was ex-pressed in both stromal fibroblast cells (98/134, 73.1%) and carcinoma cells (102/134, 76.1%). All 4 pancreatic cancer cell lines expressed FAP protein at different levels. Protein bands corresponding to the proteolytically active 170-kDa seprase dimer and its 88-kDa seprase subunit were identified. Higher FAP expression in carcinoma cells was associated with tumor size (P < 0.001), fibrotic focus (P = 0.003), perineural invasion (P = 0.009) and worse clinical outcome (P = 0.0085).CONCLUSION: FAP is highly expressed in carcinoma cells and fibroblasts in PDAC tissues, and its expression is associated with desmoplasia and worse prognosis.