Diagnostic Marker For Pancreatic Cancer Research Articles

Genomic insights and prognostic significance of novel biomarkers in pancreatic ductal adenocarcinoma: A comprehensive analysis

Pancreatic ductal adenocarcinoma (PDAC) is a highly prevalent digestive system malignancy, with a significant impact on public health, especially in the elderly population. The advent of the Human Genome Project has opened new avenues for precision medicine, allowing researchers to explore genetic markers and molecular targets for cancer diagnosis and treatment. Despite significant advances in genomic research, early diagnosis of pancreatic cancer remains elusive due to the lack of highly sensitive and specific markers. Therefore, there is a need for in-depth research to identify more precise and reliable diagnostic markers for pancreatic cancer. In this study, we utilized a combination of public databases from different sources to meticulously screen genes associated with prognosis in pancreatic cancer. We used gene differential analysis, univariate cox regression analysis, least absolute selection and shrinkage operator (LASSO) regression, and multivariate cox regression analysis to identify genes associated with prognosis. Subsequently, we constructed a scoring system, validated its validity using survival analysis and ROC analysis, and further confirmed its reliability by nomogram and decision curve analysis (DCA). We evaluated the diagnostic value of this scoring system for pancreatic cancer prognosis and validated the function of the genes using single cell data analysis. Our analysis identifies six genes, including GABRA3, IL20RB, CDK1, GPR87, TTYH3, and KCNA2, that were strongly associated with PDAC prognosis. Clinical prognostic models based on these genes showed strong predictive power not only in the training set but also in external datasets. Functional enrichment analysis revealed significant differences between high- and low-risk groups mainly in immune-related functions. Additionally, we explored the potential of the risk score as a marker for immunotherapy response and identified key factors within the tumor microenvironment. The single-cell RNA sequencing analysis further enriched our understanding of cell clusters and six hub genes expressions. This comprehensive investigation provides valuable insights into pancreatic PDAC and its intricate immune landscape. The identified genes and their functional significance underscore the importance of continued research into improving diagnosis and treatment strategies for PDAC.

Eukaryotic translation initiation factor 2α kinase 2 in pancreatic cancer: An approach towards managing clinical prognosis and molecular immunological characterization.

Most patients with pancreatic cancer are already in the late stages of the disease when they are diagnosed, and pancreatic cancer is a deadly disease with a poor prognosis. With the advancement of research, immunotherapy has become a new focus in the treatment of tumors. To the best of our knowledge, there is currently no reliable diagnostic or prognostic marker for pancreatic cancer; therefore, the present study investigated the potential of eukaryotic translation initiation factor 2α kinase 2 (EIF2AK2) as a predictive and diagnostic marker for pancreatic cancer. Immunohistochemical staining of clinical samples independently verified that EIF2AK2 expression was significantly higher in clinically operated pancreatic cancer tissues than in adjacent pancreatic tissues., and EIF2AK2 expression and differentially expressed genes (DEGs) were identified using downloadable RNA sequencing data from The Cancer Genome Atlas and Genomic Tumor Expression Atlas. In addition, Gene Ontology/Kyoto Encyclopedia of Genes and Genomes analyses and immune cell infiltration were used for functional enrichment analysis of EIF2AK2-associated DEGs. The clinical importance of EIF2AK2 was also determined using Kaplan-Meier survival, Cox regression and time-dependent survival receiver operating characteristic curve analyses, and a predictive nomogram model was generated. Finally, the functional role of EIF2AK2 was assessed in PANC-1 cells using a short hairpin RNA-EIF2AK2 knockdown approach, including CCK-8, wound healing assay, cell cycle and apoptosis assays. The findings suggested that EIF2AK2 may have potential as a diagnostic and prognostic biomarker for patients with pancreatic cancer. Furthermore, EIF2AK2 may provide a new therapeutic target for patients with pancreatic cancer.

Serum exosomal miR-451a acts as a candidate marker for pancreatic cancer.

The aim of this study was to explore the diagnostic efficiency of serum exosomal miR-451a as a novel biomarker for pancreatic cancer. Serum samples were collected prior to treatment. First, we analyzed microRNA (miRNA) profiles in serum exosomes from eight pancreatic cancer patients and eight healthy volunteers. We then validated the usefulness of the selected exosomal miRNAs as biomarkers in another 191 pancreatic cancer patients, 95 pancreatic benign disease (PB) patients, and 90 healthy controls. The expression of miR-451a in serum-derived exosomes from pancreatic cancer patients was significantly upregulated compared with those from PB patients and healthy individuals. Serum exosomal miR-451a showed excellent diagnostic power in identifying pancreatic cancer patients. In addition, exosomal miR-451a showed a significant association with clinical stage and distant metastasis in pancreatic cancer, and the expression level of serum exosomal miR-451a was sensitive to therapy and relapse. Serum exosomal miR-451a might serve as a novel diagnostic marker for pancreatic cancer.

Plasma-Derived Exosome MiR-19b Acts as a Diagnostic Marker for Pancreatic Cancer.

BackgroundDiagnosis of pancreatic cancer (Pca) is challenging. This study investigated the value of plasma-derived exosome miR-19b (Exo-miR-19b) in diagnosing patients with Pca.MethodsPlasma was collected from 62 patients with Pca, 30 patients with other pancreatic tumor (OPT), 23 patients with chronic pancreatitis (CP), and 53 healthy volunteers. MiR-19b levels in plasma-derived exosomes were detected.ResultsPlasma-derived Exo-miR-19b levels normalized using miR-1228 were significantly lower in Pca patients than in patients with OPT, CP patients, and healthy volunteers. The diagnostic values of Exo-miR-19b normalized using miR-1228 were superior to those of serum cancer antigen 19-9 (CA19-9) in differentiating Pca patients from healthy volunteers (area under the curve (AUC): 0.942 vs. 0.813, p = 0.0054), potentially better than those of CA19-9 in differentiating Pca patients from CP patients (AUC: 0.898 vs. 0.792, p = 0.0720), and equivalent to those of CA19-9 in differentiating Pca patients from patients with OPT (AUC: 0.810 vs. 0.793, p = 0.8206). When normalized using Caenorhabditis elegans miR-39 (cel-miR-39), Exo-miR-19b levels in Pca patients were significantly higher than those in patients with OPT, CP patients, and healthy volunteers. The diagnostic values of Exo-miR-19b normalized using cel-miR-39 were equivalent to those of CA19-9 in differentiating Pca patients from healthy volunteers (AUC: 0.781 vs. 0.813, p = 0.6118) and CP patients (AUC: 0.672 vs. 0.792, p = 0.1235), while they were inferior to those of CA19-9 in differentiating Pca patients from patients with OPT (AUC: 0.631 vs. 0.793, p = 0.0353).ConclusionPlasma-derived Exo-miR-19b is a promising diagnostic marker for Pca. The diagnostic value of plasma-derived Exo-miR-19b normalized using miR-1228 is superior to that of serum CA19-9 in differentiating patients with Pca from healthy volunteers.

A Circulating Exosome RNA Signature Is a Potential Diagnostic Marker for Pancreatic Cancer, a Systematic Study.

Simple SummaryMost patients with pancreatic cancer are diagnosed at an advanced stage due to the lack of tools with high sensitivity and specificity for early detection. Aberrant gene expression occurs in pancreatic cancer, which can be packaged into nanoparticles (also known as exosomes or nano-sized extracellular vesicles) and then released into blood. In this study, we aimed to evaluate the diagnostic value of a circulating exosome RNA signature in pancreatic cancer. Our findings indicate that the circulating exosome RNA signature is a potential marker for the early detection or diagnosis of pancreatic cancer.Several exosome proteins, miRNAs and KRAS mutations have been investigated in the hope of carrying out the early detection of pancreatic cancer with high sensitivity and specificity, but they have proven to be insufficient. Exosome RNAs, however, have not been extensively evaluated in the diagnosis of pancreatic cancer. The purpose of this study was to investigate the potential of circulating exosome RNAs in pancreatic cancer detection. By retrieving RNA-seq data from publicly accessed databases, differential expression and random-effects meta-analyses were performed. The results showed that pancreatic cancer had a distinct circulating exosome RNA signature in healthy individuals, and that the top 10 candidate exosome RNAs could distinguish patients from healthy individuals with an area under the curve (AUC) of 1.0. Three (HIST2H2AA3, LUZP6 and HLA-DRA) of the 10 genes in exosomes had similar differential patterns to those in tumor tissues based on RNA-seq data. In the validation dataset, the levels of these three genes in exosomes displayed good performance in distinguishing cancer from both chronic pancreatitis (AUC = 0.815) and healthy controls (AUC = 0.8558), whereas a slight difference existed between chronic pancreatitis and healthy controls (AUC = 0.586). Of the three genes, the level of HIST2H2AA3 was positively associated with KRAS status. However, there was no significant difference in the levels of the three genes across the disease stages (stages I–IV). These findings indicate that circulating exosome RNAs have a potential early detection value in pancreatic cancer, and that a distinct exosome RNA signature exists in distinguishing pancreatic cancer from healthy individuals.

Meta-analysis of the Diagnostic Performance of Circulating MicroRNAs for Pancreatic Cancer

Background: Numerous studies have suggested that differentially expressed miRNAs may be promising diagnostic markers for pancreatic cancer (PC), but the results are inconsistent. We aimed to summarize the diagnostic accuracy of circulating miRNAs, carbohydrate antigen 19-9 (CA19-9), and the combination of miRNAs and CA19-9.Material and Methods: A literature search of online databases including PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI) and WanFang was conducted. Relative data were extracted from eligible included studies, and a meta-analysis was performed.Results: A total of 46 studies involving 4,326 PC patients and 4,277 non-PC controls were included. The pooled sensitivity (SEN), specificity (SPE) and AUC of the circulating miRNAs for differentiating PC patients from non-PC controls were 0.79 (0.77-0.81), 0.77 (0.75-0.79), and 0.85 (0.81-0.87), respectively. The combination of miRNAs and CA19-9 greatly improved the SEN, SPE and AUC to 0.84 (0.80-0.87), 0.91 (0.89-0.93) and 0.94 (0.92-0.96), respectively. Moreover, circulating miRNAs also yielded an acceptable diagnostic accuracy for early-stage PC with a SEN of 0.79 (0.76-0.82), a SPE of 0.74 (0.68-0.79) and an AUC of 0.81 (0.77-0.84).Conclusion: Circulating miRNAs exhibited satisfactory diagnostic performance for PC and even early-stage PC. The combination of circulating miRNAs and CA19-9 can further improve the diagnostic accuracy, providing a novel strategy for PC diagnosis.

Mir-320b Inhibits Pancreatic Cancer Cell Proliferation by Targeting FOXM1.

Pancreatic Ductal Adenocarcinoma (PDAC) is the most common and deadly cancer. Surgical resection is the only possible cure for pancreatic cancer but often has a poor prognosis, and the role of adjuvant therapy is urgently explored. MicroRNAs (miRNAs) play a very important role in tumorigenesis by regulating the target genes. In this study, we identified miR-320b lower-expressed in human pancreatic cancer tissues but relatively higher-expressed in the adjacent non-tumor tissues. Consistently, the expression of miR-320b in different pancreatic cancer cell lines was significantly lower than the normal pancreatic cells. In order to identify the effects of miR-320b on cell growth, we overexpressed miR-320b in PANC-1 and FG pancreatic cancer cell lines, CCK8 and BrdU incorporation assay results showed that miR-320b inhibited cell proliferation. We next predicted miR-320b targeted FOXM1 (Forkhead box protein M1) and identified the negative relationship between miR-320b and FOXM1. We also demonstrated that elevated miR- 320b expression inhibited tumor growth in vivo. All of these results showed that miR-320b suppressed pancreatic cancer cell proliferation by targeting FOXM1, which might provide a new diagnostic marker for pancreatic cancer.

Associations of volumetric whole-body 18F-FDG PET/CT parameters with the CA 19-9 level and haemogram parameters in pancreatic adenocarcinoma.

The present study compared metabolic and volumetric fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) parameters [metabolic tumour volume (MTV), total lesion glycolysis (TLG), and maximum standardized uptake value (SUVmax)] with carbohydrate antigen (CA) 19-9 tumour marker levels and haemogram parameters [(neutrophil-lymphocyte ratio, mean platelet volume (MPV), and platelet-lymphocyte ratio] as prognostic and diagnostic markers of pancreatic cancer. A total of 66 patients who underwent 18F-FDG PET/CT in our nuclear medicine clinic between February 2017 and March 2019, and had a diagnosis of pancreatic adenocarcinoma, were included in this retrospective study. The enrolled patients had not been administered steroids or operated on. Among these patients, whose haemogram parameters and tumour markers could not be assessed by PET/CT within the same week were excluded. The MTV, TLG, and SUVmax values were calculated from primary tumours and metastases in all patients. Spearman's rho correlation, used to examine the relationship between the CA 19-9 level and PET parameters, revealed a statistically significant positive correlation of CA 19-9 with the whole-body MTV (MTVWB) (P<0.001) and whole-body TLG (TLGWB) (P<0.001). Although no significant relationship was found between the neutrophil count and TLGWB according to Spearman's rho correlation, in an artificial neural network using the hidden layer activation function, the neutrophil count showed the strongest association with MTVWB among all included variables. The primary pancreatic tumour MTV and TLG values showed statistically significant positive correlations with the metastases MTV, metastases TLG, MTVWB, and TLGWB values. The CA 19-9 level is considered an important marker of tumour load; it shows a statistically significant positive correlation with parameters such as MTVWB and TLGWB, which provide a measure of the whole-body tumour load. It appears that the MTV and TLG values of the primary pancreatic tumour could also be used as markers of the whole-body tumour load, given their associations with MTVWB and TLGWB.

Expressions of serum miRNA-126 and miRNA-30c in patients with pancreatic cancer and their clinical significances

Objective To investigate the expressions of serum miRNA-126 (miR-126) and miRNA-30c (miR-30c) in patients with pancreatic cancer, and to analyze the relationship with the occurrence of pancreatic cancer as well as the diagnostic value. Methods A total of 110 patients with pancreatic cancer diagnosed at the 928th Hospital of the Joint Service Support Force of PLA from January 2014 to December 2018 were selected, and 110 healthy people were also selected as the control group. The expression levels of serum miR-126 and miR-30c of 110 patients and the healthy controls were detected by using real-time quantitative polymerase chain reaction (qRT-PCR), and their relationship with clinicopathological features of pancreatic cancer was analyzed. Results The levels of serum miR-126 and miR-30c in pancreatic cancer group were lower than those in the healthy control group (0.43±0.12 vs. 1.02±0.27, t = 19.394, P 0.05), but related with tumor size, differentiation degree, TNM stage and lymph node metastasis (all P < 0.05). High expression levels of serum miR-126 and miR-30c were protective factors for pancreatic cancer (all P < 0.05), while smoking, drinking and gallstones were risk factors for pancreatic cancer (all P < 0.05). The area under the curve of combined detection of serum miR-126 and miR-30c for diagnosis of pancreatic cancer was 0.906, the sensitivity was 90.80%, and the specificity was 82.20%. Conclusions The expression levels of serum miR-126 and miR-30c in patients with pancreatic cancer are low. Both of them may be involved in the occurrence and development of pancreatic cancer, and may be used as early diagnostic markers of pancreatic cancer. Key words: Pancreatic neoplasms; miRNA-126; miRNA-30c; Diagnosis

Expression and Localization of Huntingtin-Associated Protein 1 (HAP1) in the Human Digestive System.

Huntingtin-associated protein 1 (HAP1) is a neuronal protein that is predominantly expressed in neurons in the brain. HAP1 is critical for maintenance of neuronal survival as well as regulation of food intake and body weight in animals. In addition to the critical role of HAP1 in the central nervous system, HAP1 is also found in endocrine cells, raising an interesting issue of whether HAP1 is expressed in the digestive system. To examine the expression and localization of HAP1 in the human gastrointestinal tract and to compare the differences of the HAP1 expression between benign and malignant tissues in the digestive system. We used Western blot and immunohistochemistry to examine the expression and distribution of HAP1 in the human gastrointestinal tract tissues. We observed that the presence of HAP1-positive cells in the gastrointestinal tract was not uniform with immunohistochemistry staining. Western blot revealed that only one isoform (75KD) HAP1 was present in the human gastrointestinal system. Interestingly, the expression of HAP1 was higher in the stomach than other regions of the gastrointestinal tract and was at the lowest level in the intestine. We also found that HAP1 was unlikely altered in benign gastric polyps, but was downregulated in pancreatic cancer. This is the first study showing the differential expression and location of HAP1 in the human digestive system. These findings suggested that HAP1 may have cell-type-dependent function in the gastrointestinal tract and may serve as a diagnostic marker for pancreatic cancer.

Fractalkine/CX3CR1 induces apoptosis resistance and proliferation through the activation of the AKT/NF-κB cascade in pancreatic cancer cells.

Fractalkine (FKN, CX3CL1) is highly expressed in a majority of malignant solid tumours. Fractalkine is the only known ligand for CX3CR1. In this study, we performed an analysis to determine the effects of fractalkine/CX3CR1 on modulating apoptosis and explored the related mechanisms. The expression of fractalkine/CX3CR1 was detected by immunohistochemistry and western blotting. The levels of AKT/p-AKT, BCL-xl, and BCL-2 were detected by western blotting. Then, the effects of exogenous and endogenous fractalkine on the regulation of tumour apoptosis and proliferation were investigated. The mechanism of fractalkine/CX3CR1 on modulating apoptosis in cancer cells through the activation of AKT/NF-κB/p65 signals was evaluated. The effect of fractalkine on regulating cell cycle distribution was also tested. Fractalkine, AKT/p-AKT, and apoptotic regulatory proteins BCL-xl and BCL-2 were highly expressed in human pancreatic cancer tissues. In vitro, fractalkine/CX3CR1 promoted proliferation and mediated resistance to apoptosis in pancreatic cancer cells. The antiapoptotic effect of fractalkine was induced by the activation of AKT/NF-κB/p65 signalling in pancreatic cancer cells. The NF-κB/p65 contributes to promote the expressions of BCL-xl and BCL-2 and reduce caspase activity, thereby inhibiting apoptotic processes. Treatment with fractalkine resulted in the enrichment of pancreatic cancer cells in S phase with a concomitant decrease in the number of cells in G1 phase. The present study demonstrated the function of fractalkine in the activation of the AKT/NF-κB/p65 signalling cascade and mediation of apoptosis resistance in pancreatic cancer cells. Fractalkine/CX3CR1 could serve as a diagnostic marker and as a potential target for chemotherapy in early stage pancreatic cancer. Pancreatic cancer is characterized by local recurrence, neural invasion, or distant metastasis. The present study demonstrated the overexpression of fractalkine/CX3CR1 in pancreatic cancer tissues, indicating its important role in the tumourigenesis of pancreatic cancer, and suggested that the overexpression of fractalkine/CX3CR1 could serve as a diagnostic marker for pancreatic cancer. Moreover, we reveal the mechanism that fractalkine functions on the activation of the AKT/NF-κB/p65 signalling cascade and regulation of the antiapoptosis process in pancreatic cancer cells. Fractalkine/CX3CR1 could serve as an effective therapeutic target of chemotherapeutic and biologic agents in early stage pancreatic cancer.

Distinct prognostic values of alcohol dehydrogenase mRNA expression in pancreatic adenocarcinoma.

BackgroundAlcohol dehydrogenase (ADH) isoenzymes have been reported as a potential diagnostic marker for pancreatic cancer, but their prognostic value in pancreatic cancer remains unclear. The aim of this investigation was to identify the prognostic value of ADH genes in human patients with pancreatic adenocarcinoma (PAAD).Materials and methodsAn RNA sequencing dataset and corresponding survival profiles of PAAD were obtained from The Cancer Genome Atlas. Survival analysis and gene set enrichment analysis were used to investigate the prediction value and potential mechanism of ADH genes in PAAD prognosis.ResultsSurvival analysis of ADH genes suggests that a high expression of ADH1A (adjusted P=0.037, adjusted hazard ratio [HR] =0.627, 95% CI =0.404–0.972) and ADH6 (adjusted P=0.018, adjusted HR =0.588, 95% CI =0.378–0.914) were associated with a significantly decreased risk of death, while a high expression of ADH5 was associated with a significantly increased risk of death (adjusted P=0.043, adjusted HR =1.564, 95% CI =1.013–2.414). Joint effects analysis of three ADH gene prognostic markers suggests that the prognosis difference for any marker combination was more significant than that for any individual marker. The potential mechanism of ADH1A and ADH6 in PAAD prognosis was that a high expression of ADH1A and ADH6 was involved in the P450 pathway and biological processes, while high ADH5 expression was involved in transforming growth factor β regulation-related pathways and biological processes, Wnt, the cell cycle, ErbB, and mitogen-activated protein kinase signaling pathways.ConclusionOur data suggest that ADH1A, ADH5, and ADH6 expression may be potential prognostic markers of PAAD and in combination have a strong interaction and better predictive value for PAAD prognosis.

Microelements as diagnostic markers of pancreatic cancer

Pancreatic cancer is the eighth most commonly diagnosed cancer in the developed world and has one of the worst prognoses of any malignancy with 98% succumbing to their disease within 5 years. Little is known about the etiology of the disease despite significant new insights into the mutation signatures common this disease. Changes in microelements serum levels are reported in pancreatic cancer. In the current study we have examined the levels of Se, Cu, Fe, Zn and Mg in a moderately sized pancreatic cancer population and compared it to a healthy age-matched population.

DNA Hypermethylation as a Blood-Based Marker for Pancreatic Cancer: A Literature Review.

The aim is to review genes aberrantly methylated in pancreatic cancer. This review focuses on DNA promoter hypermethylation in plasma and serum to describe the most promising genes that may be useful as minimally invasive diagnostic blood-based markers for pancreatic cancer. A systematic search of the literature was performed using the PubMed and EMBASE databases. The following MeSH terms and free text were used: pancreatic disease, pancreatic cancer, pancreatic neoplasm, methylation, DNA hypermethylation, CG rich sequence, CpG island, cell-free DNA, blood, plasma, serum, fluids, and secretions. In total, 720 articles were found. Eight studies on cell-free DNA promoter hypermethylation in plasma or serum and 2 studies on hypermethylation in whole blood/leukocyte DNA from patients with pancreatic cancer were identified. The search for a hypermethylated marker in cell-free DNA is characterized by a few small studies lacking well-defined control groups. No single gene has been identified as a diagnostic marker. Because of insufficient power, none of the genes examined have the potential to work as an individual diagnostic marker, suggesting that a panel of several genes is needed. Further research is warranted before a blood-based diagnostic marker for pancreatic cancer based on promoter hypermethylation can be applied clinically.

Integrative analysis of multi-omics data for identifying multi-markers for diagnosing pancreatic cancer.

BackgroundmicroRNA (miRNA) expression plays an influential role in cancer classification and malignancy, and miRNAs are feasible as alternative diagnostic markers for pancreatic cancer, a highly aggressive neoplasm with silent early symptoms, high metastatic potential, and resistance to conventional therapies.MethodsIn this study, we evaluated the benefits of multi-omics data analysis by integrating miRNA and mRNA expression data in pancreatic cancer. Using support vector machine (SVM) modelling and leave-one-out cross validation (LOOCV), we evaluated the diagnostic performance of single- or multi-markers based on miRNA and mRNA expression profiles from 104 PDAC tissues and 17 benign pancreatic tissues. For selecting even more reliable and robust markers, we performed validation by independent datasets from the Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA) data depositories. For validation, miRNA activity was estimated by miRNA-target gene interaction and mRNA expression datasets in pancreatic cancer.ResultsUsing a comprehensive identification approach, we successfully identified 705 multi-markers having powerful diagnostic performance for PDAC. In addition, these marker candidates annotated with cancer pathways using gene ontology analysis.ConclusionsOur prediction models have strong potential for the diagnosis of pancreatic cancer.

2014 American Pancreatic Association presidential address.

I join my friend and esteemed colleague Dr Tooru Shimosegawa for this invitation to join us for a magnificent meeting planned at the Hapuna Resort on the Big Island of Hawaii. We feel that this is the perfect location because of its quiet, peaceful, and beautiful surroundings that will allow us an unparalleled opportunity to make significant progress in our joint efforts to share research findings and ideas to improve research and better patient outcomes in the pancreas world. We have planned the meeting to take advantage of the complementary talents of members of both the Japan Pancreas Society and the American Pancreatic Association (APA) as well our admired colleagues from other countries. For this meeting, we have placed a special emphasis on addressing strategies to develop early diagnostic markers for pancreatic cancer and to move forward in developing treatments for acute pancreatitis along with metrics for measuring the quality and performance of the care. We specifically want to thank the Kenner Foundation for sponsoring a workshop devoted to strategies on early diagnostics for pancreatic cancer and the Hirshberg Foundation for their continued support of topics in pancreatic cancer. I join Dr Shimosegawa in thanking Dr Ashok Saluja for his inspiration in suggesting the site for our meeting and ensuring that we continue this collaboration between our societies and Dr Kiochi Takehara for his magnificent organizational skills in helping us to rapidly come to consensus on the planning aspects of the meeting. We also thank Erin Brudvik in the APA office for her tireless efforts to arrange each and every detail of the meeting. As Dr Shimosegawa indicated, we are blessed to have had a long history of meaningful interactions between our societies initiated by the APA and the Japan Pancreas Society pioneers. We are entrusted to continue this tradition with the expectation that our combined efforts will have a significant and beneficial impact for patients who develop pancreatic diseases. Thank you for joining us and we promise to exceed your expectations.

Increased N-glycosylation of Asn⁸⁸ in serum pancreatic ribonuclease 1 is a novel diagnostic marker for pancreatic cancer.

Alterations of carbohydrate structures in cancer cells are the most promising targets for developing clinical diagnostic reagents. Pancreatic cancer is one of the most difficult cancers to diagnose because it lacks definitive symptoms. Two antibodies were raised against human pancreatic ribonuclease 1 that bind to the enzyme containing unglycosylated Asn88, but not when its Asn88 is N-glycosylated. Differential studies using these antibodies in immunoassays and Western blot analyses showed a significant increase in the serum levels of pancreatic ribonuclease 1 containing N-glycosylated Asn88 in pancreatic cancer patients compared with normal human subjects. Focusing on the increase in an N-glycosylated Asn residue of serum pancreatic ribonuclease 1, specifically Asn88, affords a new diagnostic marker for pancreatic cancer. This is the first report of a diagnostic cancer marker that takes advantage of the presence or absence of N-glycosylation at a specific Asn residue of a glycoprotein.

Cutaneous metastasis from pancreatic cancer: A case report and systematic review of the literature.

Cutaneous metastasis from pancreatic cancer is uncommon, therefore, the outcome of this progression has rarely been investigated. The aim of the present report was to evaluate the clinical characteristics of patients exhibiting cutaneous metastasis from pancreatic cancer. Thus, the current report presents a rare case of cutaneous metastatic disease from pancreatic cancer and describes a systematic review of the literature. A total of 54 articles comprising 63 cases were included for analysis. The relevant clinical and pathological characteristics, as well as the treatment strategies and survival outcomes of this rare disease presentation were reviewed. The average patient was was aged 63.9 years and males constituted a marginally greater proportion of the cohort (61.9%). The predominant manifestation of the cutaneous metastasis was a nodule or mass (73%) and the most common site of the skin lesion was non-umbilicus rather than umbilicus. The majority (66.7%) of the skin lesions were singular, particularly in patients exhibiting Sister Mary Joseph’s nodule (90%). A wide range of histological subtypes presented, with a predominance of adenocarcinoma (84.1%). Of the cases that specified the tumor differentiation grade, 78.2% were moderately or poorly differentiated. Immunohistochemistry revealed that cytokeratin (CK)20-negative, and CK7-, CK19- and carbohydrate antigen (CA)19-9-positive were specific diagnostic markers for pancreatic cancer. Distal metastases, excluding the skin, were observed in 68.3% of patients and the median survival period was 5 months. Treatment strategies including surgery, radiation, chemotherapy or a combination improved survival time from 3.0 to 8.3 months. Cutaneous metastasis from pancreatic cancer is a rare finding, often providing the only external indication of an internal malignancy and, therefore, should be considered in the differential diagnosis of skin lesions. Metastasis to the skin indicates a widespread, general dissemination and a poor prognosis. A combination of surgery, radiotherapy and chemotherapy appears to result in improved survival rates.

NPTX2 Hypermethylation in Pure Pancreatic Juice Predicts Pancreatic Neoplasms

The neuronal pentraxin II (NPTX2) gene is methylated in over 90% primary pancreatic cancer tissues but rarely in normal pancreatic ductal epithelia. Here, the authors investigated the utility of methylated NPTX2 as a diagnostic marker for pancreatic cancer in pure pancreatic juice samples of patients with benign and malignant pancreatic diseases, including pancreatic cancer, intraductal papillary mucinous neoplasm or chronic pancreatitis using methylation-specific polymerase chain reaction (MSP) and quantitative MSP. MSP assays revealed that the incidence of aberrant NPTX methylation in pure pancreatic juice samples was 64.5% (20 of 31) in patients with pancreatic cancer, 70.0% (7 of 10) in patients with malignant intraductal papillary mucinous neoplasm, 33.3% (2 of 6) in patients with benign intraductal papillary mucinous neoplasm and 21.7% (5 of 23) in patients with chronic pancreatitis. NPTX2 hypermethylation in patients with chronic pancreatitis was significantly lower than that of pancreatic cancer (P<0.01) or patients with intraductal papillary mucinous neoplasm (P<0.05). At a cutoff value of 1.39 for quantitative MSP, the incidence of aberrant NPTX2 methylation was 61.3% (19 of 31) in patients with pancreatic cancer, 50.0% (5 of 10) in patients with malignant intraductal papillary mucinous neoplasm, 0% in patients with benign intraductal papillary mucinous neoplasm and 8.7% (2 of 23) in patients with chronic pancreatitis. There was a significant difference in NPTX2 methylation between pancreatic cancer and chronic pancreatitis (P<0.01). Our findings indicate that detection of aberrant methylation of NPTX2 in pure pancreatic juice samples could be useful as a molecular marker to discriminate between patients with malignant and benign disease of the pancreas.

Detection of pancreatic cancer using serum protein profiling

BackgroundCurrently, no suitable biomarkers for the early detection of pancreatic cancer (PC) are available. Proteins present in the serum could reflect a state of the disease. In this study, these profiles as a diagnostic marker for PC were evaluated. MethodsSerum samples were obtained from PC patients (n = 50 calibration set, n = 39 validation set) and healthy volunteers (n = 110 and n = 75 respectively) according to a uniform standardized collection and processing protocol. For peptide and protein isolation, automated solid‐phase extraction (SPE) with Weak Cation Exchange (WCX) magnetic beads (MB) was performed using a 96‐channel liquid handling platform. Protein profiles were obtained by mass spectrometry (MS) and evaluated by linear discriminant analysis with double cross‐validation. ResultsA discriminating profile for PC has been identified, with a sensitivity of 78% and a specificity of 89% in the calibration set with an area under the curve (AUC) of 90%. These results were validated with a sensitivity of 74% and a specificity of 91% (AUC 90%). ConclusionSerum profiles of healthy controls and PC can be discrimated between. Further research is warranted to evaluate specificity and whether this biosignature can be used for early detection in a high risk population.