BackgroundThe secreted protein acidic and rich in cysteine (SPARC) plays a pivotal role in regulating cell-matrix interactions and tumor angiogenesis, proliferation, and migration. Detection of SPARC gene methylation may be useful as a tumorigenesis marker for early detection of pancreatic cancer.MethodsMethylation of the SPARC gene transcriptional regulation region (TRR) was detected using bisulfite-specific (BSP) PCR-based sequencing analysis in 40 cases of pancreatic cancer and the adjacent normal tissues, 6 chronic pancreatitis tissues, and 6 normal pancreatic tissues. BSP cloning-based sequencing analysis was also performed in selected cases. Clinicopathological data from the cancer patients were collected and analyzed.ResultsAnalysis of SPARC gene TRR methylation showed two hypermethylation wave peak regions: CpG Region 1 (CpG site 1-7) and CpG Region 2 (CpG site 8-12). Pancreatic tissues have shown methylation in both regions with gradual increases from normal, chronic pancreatitis, and adjacent normal tissues to cancerous tissues. However, Methylation of CpG Region 2 was more sensitive than CpG Region 1 in pancreatic tumorigenesis. Furthermore, the methylation level of CpG Region 2 was associated with increased tumor size and exposure to the risk factors (tobacco smoke and alcohol consumption) for developing pancreatic cancer.ConclusionMethylation of the SPARC gene, specifically CpG Region 2, may be an early event during pancreatic tumorigenesis and should be further evaluated as a tumorigenesis marker for early detection of pancreatic cancer.
Our method for the detection of KRAS gene mutations may be useful to supplement histo/cytopathologic evaluations for pancreatic cancer, and is superior to serum CA19-9 in EUS-FNAB histo/cytopathology-indeterminate patients. Results warrant further verification in other patient populations.
Analyses of pancreatic juice by proteomics have identified many proteins that are overabundant in pancreatic cancer (PC) juice. The mechanism by which secretion of these proteins occur remains unclear. Pancreatic juice was collected from patients with three pancreatic diseases: PC, chronic pancreatitis (CP), and simple choledocholithiasis (CDS), and analyzed by 2-DE, MALDI-TOF/MS, and Western blot. Five PC cell lines, 30 PC tissues and their corresponding adjacent pancreatic tissues were used to validate the expression of genes which code for overabundant proteins in PC juice. The mRNA and protein levels were measured by RT-PCR and immunohistochemistry, respectively. Using proteomics, it was demonstrated that the protein transthyretin (TTR) was upregulated more than 2-fold in PC juice compared with CP and CDS, while apolipoprotein A-I, lithostathine, and regenerating islet-derived 1 beta precursor were downregulated more than 2-fold. Western blots confirmed that TTR was overabundant in the PC juice. However, TTR mRNA was not detected in any of the five PC cell lines, and was only detected in islet cells. By microscopy, it was shown that islet architecture was almost completely destroyed, and the islet's maximum diameter appeared larger in PC tissues than in normal. Some overabundant proteins in PC juice, such as TTR expressed only in islets, leak into the pancreatic ductal system due to hyperplasia and architectural damage in PC tissues. The destruction of organ and tissue architecture by tumor growth may result in novel tumor markers even if the markers are not secreted directly by tumor cells.
Background and Objectives: The positive energy balance between caloric intake and caloric output increasing storage of triglycerides (TG) in adipocytes has made nonalcoholic fatty liver disease (NAFLD) one of the major public health problems in China. Excessive lipid deposition in the pancreas is referred to as nonalcoholic fatty pancreas disease (NAFPD). Early assessment of pancreatic fat infiltration will have an increasing role in the clinical management of the metabolic dysregulation and prevention pancreatic complications. Subjects and Methods: We retrospectively collected data of inpatients with NAFPD from EUS database between September 2012 and August 2020 at our endoscopic center. The prevalence of NAFPD and factors associated with its development were statistically analyzed. The echogenicity of the pancreas was compared to that of the left renal cortex during the EUS examination by using an existing criterion. Results: Four thousand, seven hundred and four consecutive individuals underwent EUS were enrolled. The prevalence of NAFPD was 1.2% (57/4704). Factors independently associated with NAFPD on multivariate analysis were increasing TG (odds ratios [OR] 4.65, P = 0.014), NAFLD (OR 16.76, P = 0.005) and decreasing apolipoprotein A-1 (OR 0.002, P = 0.0127). We found no association between NAFPD and age, sex, total cholesterol or hypertension. Conclusions: We found a meaningful relationship between NAFLD, dyslipidemia, and NAFPD in Chinese. We hypothesized that NAFPD was strongly correlated with ectopic fat deposition and its related abnormalities of lipid metabolism. Early diagnosis of NAFLD provides opportunities to control the progression of NAFPD.
Abstract. Pancreatic juice is a potential source of proteins associated with pancreatic cancer (PC) due to the proximity of ducts to tumor tissue. Therefore, screening of proteins in pancreatic juice from PC patients may identify new PC biomarkers. We analyzed pancreatic juice from patients with pancreatic diseases including PC, chronic pancreatitis (CP) and simple choledocholithiasis (CDS) by 2-DE. Protein spots from PC patients that changed >2-fold compared with both CP and CDS were selected and identified by mass spectrometry (MS). mRNA levels were measured by QRT-PCR in PC cell lines, PC tissues and adjacent pancreatic normal (PN) tissues. Relationships between mRNA levels in PC tissues and their clinical characteristics and promoter methylation were analyzed in PC cell lines and tissues. We found that four proteins were significantly changed in PC compared to CP and simple CDS. Two proteins were up-regulated, serine proteinase-2 (PRSS2) preproprotein and pancreatic lipaserelated protein-1 (PLRP1), and two proteins were downregulated, chymotrypsinogen B (CTRB) precursor and elastase 3B (ELA3B) preproprotein. In all PC cell lines, PRSS 2 mRNA levels were elevated, while PLRP 1 mRNA was detected in 4/5 cell lines. ELA3B mRNA was undetectable in all cell lines, but CTRB mRNA was detected in 2/5 cell lines. In PC tissues compared to PN, levels of PRSS2 mRNA were significantly higher, ELA3B significantly lower, and PLRP1 and CTRB not significantly different. Elevated PRSS2 mRNA levels correlated with high T stage. The ELA3B gene promoter had higher methylation in PC cell lines and tissues compared with PN tissues, and correlated with low ELA3B gene expression. In conclusion, comparative proteomic analysis of pancreatic juice from PC patients is a powerful method to find new PC biomarkers. Hyperexpression of the PRSS2 gene and hypermethylation of ELA3B gene promoter were associated with PC, raising the possibility of their application as new biomarkers in PC diagnosis and screening.
The vortex rope in the draft tube is considered as the major contributor to pressure pulsation at partial load (PL) conditions, which causes the hydro unit to operate unstably. Based on the prototype Francis turbine HLA551-LJ-43 in the laboratory, J-grooves are designed on its conical section in this paper. We used numerical simulation to study the effect of the J-grooves on vortex suppression and energy dissipation in the draft tube. Four typical operating conditions were chosen to analyze the vortex suppression; the corresponding flow ratios Q* are 100%, 82%, 69%, and 53%, respectively. Entropy production theory is used to calculate the energy losses and assess the effect of the J-groove on energy dissipation under part-load conditions. By comparing entropy production, circumferential and axial velocity components, swirl intensity, pressure pulsation, and vortex distribution in a draft tube with and without J-grooves at different operating conditions, it can be concluded that the entropy production on the wall containing a conical section with J-grooves is obviously smaller than that without J-grooves, the effects of J-grooves on reducing circumferential velocity component Vu, pressure pulsation, and weakening vortex intensity and vortex rope in the conical section are obvious, especially at part load and deep part-load operating conditions. Using J-grooves shows better performance on vortex control and energy dissipation in the draft tube of a Francis turbine at partial load conditions.
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