Deep learning-based gene selection in comprehensive gene analysis in pancreatic cancer

The selection of genes that are important for obtaining gene expression data is challenging. Here, we developed a deep learning-based feature selection method suitable for gene selection. Our novel deep learning model includes an additional feature-selection layer. After model training, the units in this layer with high weights correspond to the genes that worked effectively in the processing of the networks. Cancer tissue samples and adjacent normal pancreatic tissue samples were collected from 13 patients with pancreatic ductal adenocarcinoma during surgery and subsequently frozen. After processing, gene expression data were extracted from the specimens using RNA sequencing. Task 1 for the model training was to discriminate between cancerous and normal pancreatic tissue in six patients. Task 2 was to discriminate between patients with pancreatic cancer (n = 13) who survived for more than one year after surgery. The most frequently selected genes were ACACB, ADAMTS6, NCAM1, and CADPS in Task 1, and CD1D, PLA2G16, DACH1, and SOWAHA in Task 2. According to The Cancer Genome Atlas dataset, these genes are all prognostic factors for pancreatic cancer. Thus, the feasibility of using our deep learning-based method for the selection of genes associated with pancreatic cancer development and prognosis was confirmed.

The Expression Profile and Textural Characteristics of C595-Reactive MUC1 in Pancreatic Ductal Adenocarcinoma for Targeted Radionuclide Therapy

Improvements in the prognosis of pancreatic ductal adenocarcinoma (PDAC) rely on the development of effective treatments to target advanced disease. Mucin 1 (MUC1) is a transmembrane glycoprotein which is involved in the metastatic progression of PDAC and is a receptor-of-interest for targeted radionuclide therapy. The aim of this study was to determine the feasibility of MUC1-based targeted radionuclide therapy for PDAC, by evaluating the expression profile of MUC1 in different pancreatic cells and tissues using the C595 antibody. MUC1 expression was evaluated in four PDAC cell lines (PANC-1, BxPC-3, CAPAN-1 and AsPC-1) using flow cytometry and immunocytochemistry. Immunohistochemistry was performed on primary and metastatic PDAC, pancreatitis, pancreatic intra-epithelial neoplasia and normal pancreatic tissue samples to identify potential changes in C595-reactive MUC1 expression across different disease groups. C595-reactive MUC1 expression was found to varying degrees in the cell lines (11.5–93.1%). A pixel analysis of the immunohistochemical staining demonstrated highest MUC1 expression in primary PDAC tissue (mean pixel value of 205.4), followed by other pancreatic cancer types (204.9), pancreatic intra-epithelial neoplasia (203.8), metastatic PDAC (201.5), chronic pancreatitis (198.1) and normal pancreatic tissue (191.4). The increased expression in malignant tissues and reduced expression in benign tissues indicate that C595-reactive MUC1 is a potential target for targeted radionuclide therapy of PDAC.

Ectopia of the pancreas in the loop of the small intestine in an 8-y-o child

Ectopia of the pancreas in children is a rare congenital malformation in which normal pancreatic tissue develops in other organs, without communication with the main gland in the wall of the stomach, intestines, liver, gallbladder, Meckel's diverticulum, and the spleen. In this article, the authors cite a rare case of ectopia of the pancreas in the loop of the small intestine, which led to the development of intestinal obstruction. Girl B., eight years old, was admitted to the hospital on an emergency basis with paroxysmal abdominal pain. There was no nausea or vomiting. A contrast study of the gastrointestinal tract with barium sulfate was performed, which revealed a violation of the evacuation of the contrast medium. A laparoscopy was performed with the clinic for low intestinal obstruction. Revision of the intestine revealed a tumor-like formation measuring 6 4 cm at 60 cm from the ileocecal angle. A minilaporotomy was performed, a 10 cm section of the ileum was resected, bearing a tumor-like formation with an end-to-end anastomosis. The postoperative period is favorable. The girl was discharged from the hospital on the eighth postoperative day. On histological examination, pancreatic tissue was found in the wall of the small intestine, with duct ectasia. At the follow-up examination after one year. the patient had no complaints with normal growth and development. This clinical observation demonstrates the nonspecificity of the clinical picture and the difficulty of diagnosing pancreatic ectopia, and the advantages of minimally invasive interventions that allow diagnosing a rare pathology and its timely adequate correction.

Association of γ-aminobutyric acid type A receptor-associated protein with prognosis in patients after radical pancreatic cancer treatment

Background：Pancreatic cancer is difficult to cure and many factors influence patient prognosis, of which autophagy is a recent research hotspot, and GABARAP plays a key role in autophagy, which has been found to interfere with cancer cell survival and metastasis in a variety of tumours. In this study, we analysed the correlation between GABARAP and patient prognosis in pancreatic cancer, as well as its correlation with clinicopathological parameters and its impact on the efficacy of chemotherapy in pancreatic cancer patients.Methods: The pancreatic tissues of 76 pancreatic cancer patients after R0 resection were screened according to the criteria, and the expression levels of GABARAP were determined by using immunohistochemistry (MaxVision) to label the pancreatic cancer tissues and normal pancreatic tissue around carcinoma in these two types of specimens, and the relationship between GABARAP and other factors and the disease-free and overall survival of patients after radical pancreatic cancer treatment was evaluated by single factor survival analysis and Cox regression analysis.Results：The expression ratio of GABARAP in pancreatic cancer tissue was drastically higher than that in normal pancreatic tissue adjacent to cancer. Cox regression model evaluation showed that GABARAP and postoperative adjuvant chemotherapy were the overall survival of patients after radical pancreatic cancer Period independent prognostic indicators and both are protective factors for the prognosis of pancreatic cancer patients. Further data analysis found that postoperative chemotherapy drastically increased the total patient Survival period in GABARAP-negative patients but had no drastically effect on the patient's relapse-free survival period.Conclusion: The expression of GABARAP in pancreatic cancer tissues was drastically up-regulated, and patients with high expression of GABARAP in pancreatic cancer tissues had better prognosis, but had no drastically effect on the relapse-free survival of patients after radical operation of pancreatic cancer. The expression of GABARAP in pancreatic cancer tissues and Postoperative adjuvant chemotherapy is an independent indicator of patients' prognosis after radical pancreatic cancer resection. Both are protective factors. The high expression of GABARAP in pancreatic cancer may indicate that the adjuvant chemotherapy is low benefit.

Pharmacokinetic Analysis of Dynamic [18F]FAZA PET Imaging in Pancreatic Cancer Patient

Purpose This study assessed the pharmacokinetics of the hypoxia PET tracer, [18F]fluoroazomycin arabinoside ([18F]FAZA), in pancreatic cancer (PCa) patients and determined the optimal kinetic parameters to distinguish cancerous from normal pancreatic tissue. Method Twenty patients with pancreatic ductal adenocarcinoma underwent dynamic [ 18 F]FAZA scans. The tissue time activity curve (TAC) was analyzed using graphical methods to determine reversibility of tracer binding and with standard compartment (S2TC) model and flow modified two tissue compartment (F2TC) model, developed to incorporate transit time of tracer through the blood vessel, to estimate the kinetic parameters. The optimal parameter set to distinguish hypoxic tumors from normal tissues was determined using logistic regression. Results Both graphical and kinetic model analysis indicated that tracer was reversibly bound. According to the Akaike Information Criteria, the F2TC model fitted the tumor TAC better than the S2TC model. Total distribution volume, V T , estimated by the F2TC model for both tumor and normal pancreatic tissue was not significant but that estimated by the S2TC model was significantly different from Logan graphical analysis. The extravascular distribution volume ( DV ) and tracer dissociation rate constant ( k 4 ) can classify hypoxic PCa from normal tissue with sensitivity of 95% and negative predictive value of 89% (P<0.01). Conclusions Kinetic analysis of dynamic [ 18 F]FAZA PET can distinguish PCa from normal tissue with high sensitivity. The reversibility of [ 18 F]FAZA binding in hypoxic cells could be due to glutathionylation of the nitroreductase reduced products and their subsequent efflux from same cells via the ATP mediated multidrug resistant protein (MRP-1) efflux pump.

The WNT5A/ROR2 signaling pathway in pancreatic ductal adenocarcinoma (PDAC)

Background WNT5A/ROR2 signaling pathway has been shown to be involved in many human cancers. Its role in pancreatic ductal adenocarcinoma (PDAC) has not been clarified yet. The aim of this study was to determine the prognostic value of WNT5A-expression in conjunction with the ROR2-expression in the same tumor tissues of PDAC patients. Methods We retrospectively analyzed the expression of WNT5A and ROR2 in 117 paraffin-embedded PDAC specimens following surgical pancreatic resection by immunohistochemistry. The prognostic value of WNT5A and ROR2 was assessed using Kaplan-Meier survival curves and multivariate COX regression-models. Results High ROR2-expression was detected in 65.8% (77/117) of PDAC-tumors, in 28.2% (33/117) in tumor-stroma, and in 71.1% (65/90) of normal pancreatic tissue. High WNT5A-expression was found in 76.9% (90/117) of tumors, in 59.0% (69/117) of tumor-stroma, and in 83.0% (73/88) of normal pancreatic tissue. Spearman's correlation co-efficiency demonstrated weak association between ROR2- and WNT5A-expression in tumor (r = 0.184; p = 0.047), and no association in stroma (r = 0.036; p = 0.699). Multivariate analysis showed that regional lymph node invasion and differentiation were independent prognostic factors of survival, while ROR2- and WNT5A-expression not. Conclusions Variable expression patterns for ROR2 and WNT5A were demonstrated in PDAC and normal pancreatic tissues suggesting a role for WNT5A/ROR2 signalling pathway, not only in PDAC but also in the normal pancreatic tissue during inflammation. The lack of prognostic significance for ROR2- and WNT5A-expression in our cohort, either alone or in subgroup analysis, signifies the complexity of their role in PDAC, which is highly dependent on the different molecular receptor-ligand tissue contexts.

LHPP suppresses proliferation, migration, and invasion and promotes apoptosis in pancreatic cancer

Pancreatic cancer (PaCa) is a common malignant tumor of the digestive system with poor prognosis and no ideal treatment for inoperable patients, which is partly due to delayed diagnoses. It is recently reported that the protein histidine phosphatase LHPP is a tumor suppressor in hepatocellular carcinoma, cervical cancer, and bladder cancer. So far, there is no study on the expression level of LHPP in PaCa, and its mechanism of action on tumors is unclear. In this experiment, LHPP expression was lower in cancer tissues than that in normal pancreatic tissue, and clinicopathological results showed that LHPP expression was correlated with the degree of differentiation and lymphatic metastasis of pancreatic carcinoma. The biological characteristics of LHPP in PaCa cells were examined by the cell counting kit-8 assay, transwell assay, and monoclonal formation test. The inhibitory mechanism of LHPP in PaCa cells was determined using Western blotting and flow cytometry. The results showed that LHPP restrained PaCa cell proliferation, migration, and invasion. Increased LHPP expression promoted the apoptosis of PaCa cells through higher activation of cleaved-PARP and cleaved-Casp3 and lower activation of cIAP1. Importantly, the increase in LHPP enhanced PTEN expression and decreased the phosphorylated AKT level. Moreover, LHPP-induced apoptosis was diminished by SC79 (AKT activator) in PaCa cells. In conclusion, LHPP blocks proliferation, migration, and invasion and enhances apoptosis in PaCa cells through the PTEN/AKT signaling pathway.

A rare case of mesenteric heterotopic pancreas presenting as an inflammatory mass

Heterotopic pancreas (HP) is a rare condition, is commonly asymptomatic and found incidentally at autopsy or during abdominal surgery. HP is usually found in the upper gastrointestinal tract, particularly in the stomach, duodenum and jejunum. Mesenteric heterotopic pancreas (MHP) has been rarely described in the literature, and there has been no reported case under ten years of age. We report a unique case of a 7-year-old African boy who presented with clinical appendicitis and intraoperatively was found to have a necrotic nodular mass in the jejunal mesentery which required segmental small bowel resection. Histology revealed mesenteric heterotopic pancreas with normal pancreatic tissue. As pre-operative diagnosis of MHP is difficult; we encourage a heightened awareness of this condition as a differential diagnosis in children presenting with abdominal pain and an inflammatory mass, which will subsequently aid in the management of these patients.

Immunohistochemical expression of NEDD9, E-cadherin and γ-catenin and their prognostic significance in pancreatic ductal adenocarcinoma (PDAC)

Extensive research is being conducted to identify novel diagnostic, predictive and prognostic biomarkers for pancreatic ductal adenocarcinoma (PDAC), as only a few markers have been routinely used so far with limited success. Our aim was to assess the expression of neural precursor cell expressed developmentally down-regulated protein 9 (NEDD9), E-cadherin, and γ-catenin in PDAC in relation to clinicopathological parameters and patient survival. We also investigated if there is a correlation of NEDD9 expression with E-cadherin or γ-catenin. The protein expression was determined by immunohistochemistry in 61 PDAC and 61 samples of normal pancreatic tissue. The log rank test and Kaplan-Meier survival curve were used for survival analysis. E-cadherin and γ-catenin expressions were reduced in PDAC, and completely retained in normal pancreatic tissue. Expression of NEDD9 was significantly increased in PDAC (strong expression in 78.7% of cases and moderate in 21.3%) and reduced in normal pancreatic tissue (strong positivity in 45.9% of cases, moderate in 31.1%, and weak in 23%). There was a positive correlation between reduced E-cadherin and γ-catenin expression in PDAC (p = 0.015). The loss or reduced expression of E-cadherin had a negative impact on patient survival (p = 0.020). A negative correlation between E-cadherin expression and tumor grade was also observed (p = 0.011). Decreased E-cadherin expression was more common in male patients with PDAC (81.3% vs. 60% for females, p = 0.005). γ-catenin and NEDD9 expressions were not statistically correlated with tumor stage and grade, gender, nor with patient survival. Our results support the role of NEDD9, E-cadherin and γ-catenin proteins in PDAC, but further research should clarify in detail their mechanism of action in pancreatic cancer.