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Calcitonin gene-related peptide (CGRP) plays a diverse and intricate role in chronic low-grade inflammation and is closely related to specific cancers. It includes two subtypes, CALCA ( α CGRP) and CALCB ( β CGRP), of which α CGRP expression accounts for more than 90%. Here, we show that methylation of CALCA and CALCB in pancreatic ductal adenocarcinoma was significantly higher than that in paracancer. Western blot and immunohistochemistry showed that CGRP, p-AKT, and p-CREB in the tumor tissues were lower than those in the paracarcinoma tissues. In vivo , the expressions of p-AKT and p-CREB in the pancreatic tissues of CALCA-KO rats were also lower than those of wild type. Methylation of CALCA and CALCB is increased in pancreatic adenocarcinoma, and under that condition, p-AKT and p-CREB levels were decreased., Competing Interests: The authors have no competing interests to declare., (Copyright © 2021 Feng Gao et al.)

Background: Previous studies revealed somatic mutations of the cationic trypsinogen gene (PRSS1) in patients with chronic pancreatitis and pancreatic cancer. However, whether PRSS1 mutations trigger pancreatic cancer and/or promote malignant proliferation and metastasis in pancreatic cancer remains largely unclear, as well as the potential underlying mechanisms., Methods: In the present study, whole-exome sequencing was applied for screening, and the R116C mutation was validated by Sanger sequencing. Phosphorylation antibody array, RNA-Seq, and RT-qPCR were adopted to screen and validate that R116C mutation promoted pancreatic cancer progression via the JAK1-STAT5 pathway., Results: It showed that migration and invasion were significantly increased in R116C-bearing PANC-1 cells compared with wild type counterparts. In a transgenic mouse model of iZEG-PRSS1_R116C, primary pancreatic intraepithelial neoplasia (PanINs) was observed in the pancreatic duct., Conclusions: These findings suggested a novel pathway mediating pancreatic cancer development, with PRSS1 mutation and overexpression playing an "inside job" role in pancreatic carcinogenesis and tumor development.

Pancreatic cancer is a malignant tumor with difficulty in diagnosis and treatment and was the sixth leading cause of cancer death among both men and women in China. The 5-year relative survivals of pancreatic cancer were only 7.2% in China and the lowest level in all cancers. The proportion of estimated new cases of pancreatic cancer in China was comparatively high in East China, Northeast, North China, and Northwest and relatively low in Central China, Southwest, and South China, showing obvious regional characteristics. It implies that the incidence and mortality in the eastern region are significantly higher than those in the western region, which is consistent with the result that the incidence and mortality increased from low to middle to high urbanization areas in China, and the prevalence of diabetes increased from underdeveloped to intermediately developed to developed region.

Pancreatic cancers with poor prognosis are highly malignant, readily metastatic and of immune tolerance, mainly due to delayed detection. The metastatic progression and immune tolerance of pancreatic cancer is greatly attributed to the intercellular communication. However, exosomes are deemed to be the most important tool of intercellular communicators. Thus, we present a review of pancreatic cancer and exosomes in this article. We intensively summarize the progress of early pancreatic cancer and the relationship of the proliferation, progression and metastasis of pancreatic cancer and pancreatic cancer-derived exosomes, and propose new ideas of the study of pancreatic cancer.

This study aimed to investigate the mutations in the serine protease 1 gene (PRSS1) and the imbalance between trypsin and α1-antitrypsin in patients with pancreatic cancer. Polymerase chain reaction (PCR) was performed to amplify the sequences of PRSS1 from 65 patients with pancreatic cancer and 260 healthy controls, direct sequencing was performed, and the clinical features were analyzed. In addition, enzyme-linked immunosorbent assay (ELISA) was employed to detect serum trypsin and α1-antitrypsin in pancreatic cancer patients and healthy controls in the same period. Mutations were found at the promoter and exon 3 of the PRSS1 in patients with pancreatic cancer. That is, five patients had c.410 C > T mutation causing p.Thr 137 Met, and three patients had c. -338 T > G mutation at the promoter of the PRSS1. In patients with PRSS1 mutations, serum trypsin was 34.5 ± 18.3 ng/mL, which was significantly higher than that in normal controls (10.65 ± 6.03 ng/mL) and other pancreatic cancer (28.61 ± 8.96 ng/mL). What is more, in pancreatic cancer patients, serum α1-antitrypsin was 1.69 ± 0.86 g/L, which was comparable to that in normal controls (1.55 ± 0.53 g/L), while the ratio of serum trypsin to α1-antitrypsin was 1.46-fold to normal controls. The results presented here have provided a greater insight into the PRSS1 mutations and proteinase-inhibitor interactions occurring in pancreatic cancer.

Background: Pancreatic cancer is an aggressive disease and the fourth most common cause of cancer death across the globe. It is often not diagnosed until it is advanced. It is necessary to establish a new technology to detect DNA instabilities during the progression of pancreatic cancer and to screen for new molecular markers coupled to putative unknown oncogenes., Methods: A total of 25 pancreatic cancer tissue specimens were analyzed by sequence-characterized amplified regions (SCARs), including two pathological types (pancreatic ductal adenocarcinoma and neuroendocrine carcinoma). There were 41 random primers and eight long fragment primers used for PCR amplification, and the difference of dNTPs consumptions were detected by nano-electrochemical sensors. Once both dATP and dGTP are significantly different in oxidation current (reduce or increase simultaneously), separate the different genes by electrophoresis, then clone and sequence the genes, and carry out homology analysis., Results: Both dGTP and dATP showed good oxidation behavior on the carbon nanotube modified glassy carbon electrode. There were 32 different fragments in malignant tissues compared with normal control, among them a SNP located in 5'UTR of the leucine zipper protein 4 gene which is significantly correlated with pancreatic cancer (OR = 9.50) and it was confirmed by direct sequencing., Conclusions: SCARs combined with the nanoelectrochemical sensor can be used for screening genetic instabilities in pancreatic cancer, and leucine zipper protein 4 was a novel pancreatic cancer-related gene.

An amplified chronocoulometric Locked nucleic acid (LNA) sensor (CLS) for selective electrochemical detection of K-ras mutation was developed based on site-specific DNA cleavage of restriction endonuclease EcoRI. Thiolated-hairpin LNA probe with palindrome structure of stem was immobilized on the gold nanoparticles modified gold electrode (NG/AuE). It can be cleaved by EcoRI in the absence of K-ras mutation-type DNA (complementary with the loop part of hairpin probe), but cannot be cleaved in the presence of mutation-type DNA. The difference before and after enzymatic cleavage was then monitored by chronocoulometric biosensor. Electrochemical signals are generated by chronocoulometric interrogation of Hexaammineruthenium (III) chloride (RuHex) that quantitatively binds to surface-confined hairpin LNA probe via electrostatic interactions. The results suggested this CLS had a good specificity to distinguish the K-ras mutation-type, wild-type and non-complementary sequence. There was a good linear relationship between the charge and the logarithmic function of K-ras mutation-type DNA concentration. The detection limit had been estimated as 0.5 fM. It is possible to qualitatively and quantitatively detect K-ras point mutation in pancreatic cancer., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background and Aims: The high mortality rate of pancreatic cancer is a bottleneck for further treatment with long-term efficacy. Thus, it is urgent to identify new methods to accurately predict the early onset of pancreatic cancer. We hypothesized that the different genotypes of cationic trypsinogen (PRSS1) gene could confer susceptibility and/or resistance to pancreatic cancer in the Han Chinese population., Methods: The genotypes of PRSS1 were determined in 154 patients with pancreatic cancer and in a control group of 520 healthy individuals of Han Chinese descent. Clinical information was obtained, single-nucleotide polymorphisms (SNPs) of the PRSS1 gene were analyzed by direct sequencing, and the distribution of the genotypes were tested for Hardy-Weinberg equilibrium. Odds ratios and 95% confidence intervals were calculated by logistic regression analysis to estimate the associations between the different genotypes or haplotypes and the risk of pancreatic cancer., Results: Three SNPs (-409 C/T, -204 A/C, and c.486 C/T) were identified. A case-control analysis revealed a 0.118-fold (95% CI: 0.037-0.653), 0.842-fold (95% CI: 0.177-4.010), and 0.750-fold (95% CI: 0.519-1.085) change in risk of developing pancreatic cancer for individuals harboring these SNPs, respectively. The individuals with the -409 C/T genotype tended to have a reduced risk compared to those who carried the -409 T/T genotype. A protective effect was observed for the C(-409)-A(-204)-C(486) haplotype compared to the T(-409)-A(-204)-T(486) haplotype (OR = 0.115, 95% CI: 0.016-0.849) or compared to the T(-409)-A(-204)-C(486) haplotype (OR = 0.090, 95% CI: 0.012-0.667). Serum levels of trypsin in patients with the -409 C/T genotype were only one-fourth that of those with the -409 T/T genotype and only one-third that of the healthy controls., Conclusions: The -409 C/T genotype of PRSS1 was revealed to be a protective factor against pancreatic cancer in the Han Chinese population.

Objective: To review the feasibility of coupling the techniques of random amplified polymorphic DNA (RAPD) with carbon nanotube-based modified electrode for guanine/deoxyguanine triphosphate (dGTP) electrochemical sensing for mapping of the pancreatic cancer genetic fingerprint and screening of genetic alterations., Methods: We developed a new method to study the electrochemical behavior of dGTP utilizing carbon multiwalled nanotube (MWNT)-modified glassy carbon electrodes (GCEs). RAPD was applied for amplification of DNA samples from healthy controls and patients with pancreatic cancer under the same conditions to determine the different surplus quantity of dGTP in the polymerase chain reaction (PCR), thereby determining the difference/quantity of PCR products or template strands. Using this method we generated a genetic fingerprint map of pancreatic cancer through the combination of electrochemical sensors and gel electrophoresis to screen for genetic alterations. Cloning and sequencing were then performed to verify these gene alterations., Results: dGTP showed favorable electrochemical behavior on the MWNTs/GCE. The results indicated that the electrical signal and dGTP had a satisfactory linear relationship with the dGTP concentration within the conventional PCR concentration range. The MWNTs/GCE could distinguish between different products of RAPD. This experiment successfully identified a new pancreatic cancer-associated mutant gene fragment, consisting of a cyclin-dependent kinase 4 gene 3' terminal mutation., Conclusion: The coupling of RAPD and nanoelectrochemical sensors was successfully applied to the screening of genetic alterations in pancreatic cancer and for mapping of DNA fingerprints.