scholarly journals ROR1 and ROR2 expression in pancreatic cancer

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Dongli Liu ◽  
George Sharbeen ◽  
Phoebe Phillips ◽  
Amber L. Johns ◽  
Anthony J. Gill ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Protein Expression ◽  
Mrna Expression ◽  
Mrna Level ◽  
Prognostic Significance ◽  
Wnt Signalling ◽  
Ductal Adenocarcinoma ◽  
Clinicopathological Parameters ◽  
Cytoplasmic Staining

Abstract Background The Wnt receptors ROR1 and ROR2 are generating increased interest as cancer therapeutic targets but remain understudied in pancreatic ductal adenocarcinoma (PDAC). Compared to canonical Wnt/ β-catenin signalling, the role of noncanonical Wnt signalling in PDAC remains largely unknown. Only one study has investigated the prognostic significance of the noncanonical Wnt signalling receptor, ROR2 in PDAC. No studies have investigated the prognostic role of ROR1 in PDAC. Methods Here, we performed analysis of ROR1 and ROR2 mRNA expression in three publicly available datasets ICGC-PACA-AU (n = 81), TCGA-PAAD (n = 150) and CPTAC-PDAC (n = 137). ROR1 and ROR2 protein expression from the CPTAC-PDAC discovery cohort were also analysed. Immunohistochemistry (IHC) using the validated anti ROR1 monoclonal antibody (4A5) was performed on the Australian Pancreatic Cancer Genome Initiative (APGI) cohort of PDAC samples (n = 152). Association between ROR1 cytoplasmic staining intensity and clinicopathological parameters including stage, grade and overall survival (OS) was investigated. Results High ROR1 mRNA expression levels correlated with a favourable OS outcome in all of the ICGC-PACA-AU, TCGA-PAAD and CPTAC-PDAC cohorts. ROR1 protein expression was not associated with stage, grade or OS in the APGI cohort. Conclusion ROR1 and ROR2 have potential as prognostic markers when measured at the mRNA level in PDAC. Our IHC cohort did not support ROR1 protein expression in predicting OS, and highlighted the discrepancy of prognostic biomarkers when measured by MS, IHC and RNAseq.

scholarly journals Cancer stem cells markers associated with development and aggressive phenotype in pancreatic cancer

2020 ◽  
pp. 102-122
Author(s):  
Camila Juliano Salvador Rodrigues ◽  
Elita Ferreira da Silveira ◽  
Rafael da Silveira Vargas ◽  
Giordano Gatti de Giacomo ◽  
Marino Muxfeldt Bianchin
Keyword(s):  
Pancreatic Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Tumor Development ◽  
Staining Intensity ◽  
Ductal Adenocarcinoma ◽  
Clinicopathological Parameters ◽  
Tumor Initiating Cells ◽  
New Ideas

Background: Cancer stem cells, also known as tumor-initiating cells, are suggested to be responsible for drug resistance and cancer development due in part to their ability to self-renew themselves and differentiate into heterogeneous lineages of cancer cells. Objective: This study was designed to investigate the role of cancer stem cells in pancreatic cancer. Methods: A retrospective clinicopathological analysis was undertaken in 112 patients diagnosed with pancreatic ductal adenocarcinoma between 2005 and 2010, and immunohistochemistry was performed with antibodies against CD133, CD24, and OCT4. Positive nuclear, cytoplasmic or membrane staining for each antibody was rated on staining intensity, being classified into low/moderate or strong staining groups. Results were analyzed relative to each patient’s clinicopathological parameters. Results: There was an established relationship between the staining of the markers with some variables associated with worse prognosis, being the three markers present in most tumor cells and associated with tumor progression. We suppose that cancer stem cells are present from the beginning of tumor initiation and are intrinsically related to tumor development. Although the presence of stem cells has been associated with molecular biology of various tumors, their expression in pancreatic cancer has not yet been clinically reported. Conclusion: The presence of stem cells and their role in pancreatic cancer tumorigenesis may be considered as valuable prognostic factors, although the mechanism involved needs further investigation. Increasing insights into role of cancer stem cells and carcinogenesis can ultimately generate new ideas for molecularly based diagnostic and therapeutic approaches.

scholarly journals Decreased HECTD1 mRNA expression is associated with poor prognosis and enhanced mitochondrial cellular respiratory function in breast cancer

2021 ◽  
Author(s):  
Yasuaki Uemoto ◽  
Eriko Katsuta ◽  
Naoto Kondo ◽  
Yumi Wanifuchi-Endo ◽  
Takashi Fujita ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Multivariate Analysis ◽  
Protein Expression ◽  
Mrna Expression ◽  
Respiratory Function ◽  
Poor Prognosis ◽  
Prognostic Significance ◽  
Negative Regulator ◽  
Mesenchymal Transition

Abstract HECT domain E3 ubiquitin ligase 1 (HECTD1) has been reported to be a negative regulator of epithelial-mesenchymal transition and to decrease breast cancer invasion and metastasis. However, the clinical significance and detailed role of HECTD1 in breast cancer remain elusive. We investigated the role of HECTD1 in two large breast cancer cohorts using mRNA and protein expression, and bioinformatics. We examined the prognostic significance of HECTD1 by multivariate analysis. HECTD1 mRNA expression (HECTD1 expression) was lower in breast cancer compared with adjacent normal tissues. HECTD1 expression levels also differed among breast cancer subtypes. Decreased HECTD1 expression was significantly associated with aggressive tumour characteristics, including large tumour size and high histological grade. HECTD1 expression was inversely associated with mitochondrial cellular respiratory function and reactive oxygen species in breast cancer tissues. Multivariate analysis identified low HECTD1 mRNA expression level as an independent risk factor for disease-free (P = 0.009) and overall (P = 0.046) survival among breast cancer patients. There was no association of HECTD1 protein expression with mRNA expression and prognosis. HECTD1 mRNA expression is a candidate prognostic biomarker in breast cancer. The poor prognosis of patients with low HECTD1 mRNA expression may be associated with increased mitochondrial respiratory function.

scholarly journals A Proteomic Study on the Personalized Protein Corona of Liposomes. Relevance for Early Diagnosis of Pancreatic DUCTAL Adenocarcinoma and Biomarker Detection

2021 ◽  
Vol 2 (2) ◽  
pp. 82-93
Author(s):  
Luca Digiacomo ◽  
Francesca Giulimondi ◽  
Daniela Pozzi ◽  
Alessandro Coppola ◽  
Vincenzo La Vaccara ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Early Diagnosis ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Protein Corona ◽  
Detection Sensitivity ◽  
Ductal Adenocarcinoma ◽  
Protein Biomarkers ◽  
Ca 19.9 ◽  
Proteomic Study

Due to late diagnosis, high incidence of metastasis, and poor survival rate, pancreatic cancer is one of the most leading cause of cancer-related death. Although manifold recent efforts have been done to achieve an early diagnosis of pancreatic cancer, CA-19.9 is currently the unique biomarker that is adopted for the detection, despite its limits in terms of sensitivity and specificity. To identify potential protein biomarkers for pancreatic ductal adenocarcinoma (PDAC), we used three model liposomes as nanoplatforms that accumulate proteins from human plasma and studied the composition of this biomolecular layer, which is known as protein corona. Indeed, plasma proteins adsorb on nanoparticle surface according to their abundance and affinity to the employed nanomaterial, thus even small differences between healthy and PDAC protein expression levels can be, in principle, detected. By mass spectrometry experiments, we quantified such differences and identified possible biomarkers for PDAC. Some of them are already known to exhibit different expressions in PDAC proteomes, whereas the role of other relevant proteins is still not clear. Therefore, we predict that the employment of nanomaterials and their protein corona may represent a useful tool to amplify the detection sensitivity of cancer biomarkers, which may be used for the early diagnosis of PDAC, with clinical implication for the subsequent therapy in the context of personalized medicine.

scholarly journals Dysregulation of protein kinase C in adult depression and suicide: evidence from postmortem brain studies

2021 ◽  
Author(s):  
Ghanshyam N Pandey ◽  
Anuradha Sharma ◽  
Hooriyah S Rizavi ◽  
Xinguo Ren
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Protein Expression ◽  
Mrna Expression ◽  
Postmortem Brain ◽  
Cortical Region ◽  
Cytosol Fraction ◽  
Kinase C ◽  
Pkc Isozymes

Abstract Background Several lines of evidence suggest the abnormalities of protein kinase C (PKC) signaling system in mood disorders and suicide based primarily on the studies of PKC and its isozymes in the platelets and postmortem brain of depressed and suicidal subjects. In this study we examined the role of PKC isozymes in depression and suicide. Methods We determined the protein and mRNA expression of various PKC isozymes in the prefrontal cortical region [Brodmann area 9 (BA9)] in 24 normal control (NC) subjects, 24 depressed suicide (DS) subjects and 12 depressed non-suicide (DNS) subjects. The levels of mRNA in the prefrontal cortex (PFC) were determined by qRT-PCR and the protein expression was determined by Western blotting. Results We observed a significant decrease in mRNA expression of PKCα, PKCβI, PKCδ and PKCε and decreased protein expression either in the membrane or the cytosol fraction of PKC isozymes - PKCα, PKCβI, PKCβII and PKCδ in DS and DNS subjects compared with NC subjects. Conclusions The current study provides detailed evidence of specific dysregulation of certain PKC isozymes in the postmortem brain of DS and DNS subjects and further supports earlier evidence for the role of PKC in the platelets and brain of adult and teenage depressed and suicidal population. This comprehensive study may lead to further knowledge of the involvement of PKC in the pathophysiology of depression and suicide.

Galectin-3 is modulated in pancreatic cancer cells under hypoxia and nutrient deprivation

2020 ◽  
Vol 401 (10) ◽  
pp. 1153-1165 ◽  
Author(s):  
Antônio F. da Silva Filho ◽  
Lucas B. Tavares ◽  
Maira G. R. Pitta ◽  
Eduardo I. C. Beltrão ◽  
Moacyr J. B. M. Rêgo
Keyword(s):  
Pancreatic Cancer ◽  
Cell Death ◽  
Mrna Expression ◽  
Cancer Cells ◽  
Ductal Adenocarcinoma ◽  
Reverse Transcription Pcr ◽  
Pancreatic Cancer Cells ◽  
Through Flow ◽  
Galectin 3

AbstractPancreatic ductal adenocarcinoma is one of the most aggressive tumors with a microenvironment marked by hypoxia and starvation. Galectin-3 has been evaluated in solid tumors and seems to present both pro/anti-tumor effects. So, this study aims to characterize the expression of Galectin-3 from pancreatic tumor cells and analyze its influence for cell survive and motility in mimetic microenvironment. For this, cell cycle and cell death were accessed through flow cytometry. Characterization of inside and outside Galectin-3 was performed through Real-Time Quantitative Reverse Transcription PCR (qRT-PCR), immunofluorescence, Western blot, and ELISA. Consequences of Galectin-3 extracellular inhibition were investigated using cell death and scratch assays. PANC-1 showed increased Galectin-3 mRNA expression when cultivated in hypoxia for 24 and 48 h. After 24 h in simultaneously hypoxic/deprived incubation, PANC-1 shows increased Galectin-3 protein and secreted levels. For Mia PaCa-2, cultivation in deprivation was determinant for the increasing in Galectin-3 mRNA expression. When cultivated in simultaneously hypoxic/deprived condition, Mia PaCa-2 also presented increasing for the Galectin-3 secreted levels. Treatment of PANC-1 cells with lactose increased the death rate when cells were incubated simultaneously hypoxic/deprived condition. Therefore, it is possible to conclude that the microenvironmental conditions modulate the Galectin-3 expression on the transcriptional and translational levels for pancreatic cancer cells.

scholarly journals Role of Oxidative and Nitro-Oxidative Damage in Silver Nanoparticles Cytotoxic Effect against Human Pancreatic Ductal Adenocarcinoma Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-15 ◽  
Author(s):  
Ewelina Barcińska ◽  
Justyna Wierzbicka ◽  
Agata Zauszkiewicz-Pawlak ◽  
Dagmara Jacewicz ◽  
Aleksandra Dabrowska ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Pancreatic Cancer ◽  
Silver Nanoparticles ◽  
Oxidative Damage ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Cytotoxic Effect ◽  
Mrna Level ◽  
Ductal Adenocarcinoma ◽  
Adenocarcinoma Cells

Pancreatic ductal adenocarcinoma is one of the most aggressive human malignancies, where the 5-year survival rate is less than 4% worldwide. Successful treatment of pancreatic cancer is a challenge for today’s oncology. Several studies showed that increased levels of oxidative stress may cause cancer cells damage and death. Therefore, we hypothesized that oxidative as well as nitro-oxidative stress is one of the mechanisms inducing pancreatic cancer programmed cell death. We decided to use silver nanoparticles (AgNPs) (2.6 and 18 nm) as a key factor triggering the reactive oxygen species (ROS) and reactive nitrogen species (RNS) in pancreatic ductal adenocarcinoma cells (PANC-1). Previously, we have found that AgNPs induced PANC-1 cells death. Furthermore, it is known that AgNPs may induce an accumulation of ROS and alteration of antioxidant systems in different type of tumors, and they are indicated as promising agents for cancer therapy. Then, the aim of our study was to evaluate the implication of oxidative and nitro-oxidative stress in this cytotoxic effect of AgNPs against PANC-1 cells. We determined AgNP-induced increase of ROS level in PANC-1 cells and pancreatic noncancer cell (hTERT-HPNE) for comparison purposes. We found that the increase was lower in noncancer cells. Reduction of mitochondrial membrane potential and changes in the cell cycle were also observed. Additionally, we determined the increase in RNS level: nitric oxide (NO) and nitric dioxide (NO2) in PANC-1 cells, together with increase in family of nitric oxide synthases (iNOS, eNOS, and nNOS) at protein and mRNA level. Disturbance of antioxidant enzymes: superoxide dismutase (SOD1, SOD2, and SOD3), glutathione peroxidase (GPX-4) and catalase (CAT) were proved at protein and mRNA level. Moreover, we showed cells ultrastructural changes, characteristic for oxidative damage. Summarizing, oxidative and nitro-oxidative stress and mitochondrial disruption are implicated in AgNPs-mediated death in human pancreatic ductal adenocarcinoma cells.

scholarly journals Microbiome—Friend or Foe of Pancreatic Cancer?

2021 ◽  
Vol 10 (23) ◽  
pp. 5624
Author(s):  
Jaroslaw Daniluk ◽  
Urszula Daniluk ◽  
Pawel Rogalski ◽  
Andrzej Dabrowski ◽  
Agnieszka Swidnicka-Siergiejko
Keyword(s):  
Pancreatic Cancer ◽  
Treatment Effectiveness ◽  
Human Microbiome ◽  
Mechanisms Of Action ◽  
Ductal Adenocarcinoma ◽  
Overall Survival Rate ◽  
Improve Treatment ◽  
Potential Marker ◽  
Deadly Disease

Pancreatic ductal adenocarcinoma is one of the deadliest human neoplasms. Despite the development of new surgical and adjuvant therapies, the prognosis remains very poor, with the overall survival rate not exceeding 9%. There is now increasing evidence that the human microbiome, which is involved in many physiological functions, including the regulation of metabolic processes and the modulation of the immune system, is possibly linked to pancreatic oncogenesis. However, the exact mechanisms of action are poorly understood. Our review summarizes the current understanding of how the microbiome affects pancreatic cancer development and progression. We discuss potential pathways of microbe translocation to the pancreas, as well as the mechanism of their action. We describe the role of the microbiome as a potential marker of pancreatic cancer diagnosis, progression, and survival. Finally, we discuss the possibilities of modifying the microbiome to improve treatment effectiveness for this deadly disease.

scholarly journals KIF4A Regulates the Progression of Pancreatic Ductal Adenocarcinoma through Proliferation and Invasion

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Jing Chen ◽  
Cui-Cui Zhao ◽  
Fei-Ran Chen ◽  
Guo-Wei Feng ◽  
Fei Luo ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Proliferation ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Disease Free Survival ◽  
High Expression ◽  
Ductal Adenocarcinoma ◽  
Migration And Invasion

Background. Pancreatic cancer is a malignant tumor of the digestive tract, which is difficult to diagnose and treat due to bad early diagnosis. We aimed to explore the role of kinesin superfamily 4A (KIF4A) in pancreatic ductal adenocarcinoma (PDAC). Methods. We first used the bioinformatic website to screen the data of pancreatic cancer in TCGA, and KIF4A protein was detected among the 86 specimens of patients in our hospital combined with clinic-pathological characteristics and survival analysis. KIF4A loss-expression cell lines were established by RNA interference (RNAi). In addition, we performed in vitro cell assays to detect the changes in cell proliferation, migration, and invasion. The proteins involved in the proliferation and metastasis of cancer cells were also detected by western blot. The above results could be proved in vivo. Further, the correlation between KIF4A and CDC5L was analyzed by TCGA and IHC data. Results. We first found a high expression of KIF4A in pancreatic cancer, suggesting a role of KIF4A in the development of pancreatic cancer. KIF4A was found to be differentially expressed ( P < 0.05 ) among the 86 specimens of patients in our hospital and was significantly associated with PDAC TNM stages and tumor size. High KIF4A expression also significantly worsened overall survival (OS) and disease-free survival rate (DFS) ( P < 0.05 , respectively). In addition, cell proliferation, migration, and invasion were inhibited by the KIF4A-shRNA group compared with the control ( P < 0.05 , respectively). In the end, knockdown of KIF4A could inhibit tumor development and metastasis in vivo. Further, the positive correlation between KIF4A and CDC5L existed, and KIF4A might promote pancreatic cancer proliferation by affecting CDC5L expression. Conclusion. In conclusion, the high expression level of KIF4A in PDAC was closely related to poor clinical and pathological status, lymphatic metastasis, and vascular invasion. KIF4A might be involved in promoting the development of PDAC in vitro and in vivo, which might be a new therapeutic target of PDAC.

Prognostic Significance of WT1 mRNA and Anti-WT1 Antibody Levels in Peripheral Blood in Patients with Myelodysplastic Syndromes.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3821-3821
Author(s):  
Hideto Tamura ◽  
Kazuo Dan ◽  
Norio Yokose ◽  
Rika Iwakiri ◽  
Masatsugu Ohta ◽  
...  
Keyword(s):  
Immune Response ◽  
Mrna Expression ◽  
Myelodysplastic Syndromes ◽  
Peripheral Blood ◽  
Quantitative Polymerase Chain Reaction ◽  
Mrna Level ◽  
Prognostic Significance ◽  
Refractory Anemia ◽  
Mrna Levels ◽  
Disease Subtype

Abstract Abstract 3821 Poster Board III-757 (INTRODUCTION) The Wilms tumor gene (WT1) message is overexpressed in tumor cells from various solid cancers as well as hematologic malignancies including myelodysplastic syndromes (MDS). We reported previously that WT1 mRNA expression in peripheral blood mononuclear cells (PBMCs) as well as bone marrow (BM) cells increased with the aggressiveness of MDS disease subtype as defined by the French-American-British (FAB) classification and that a humoral immune response, IgG- or IgM-type anti-WT1 antibody (Ab) expression, was detected in sera from most MDS patients. In this study, we investigated whether WT1 mRNA expression and anti-WT1 Ab titers in PB were associated with prognosis in MDS patients by examining their long-term follow-up data. (METHODS AND RESULTS) (1) WT1 mRNA expression in PBMCs was examined in 80 patients: 35 with refractory anemia (RA); 5 with RA with ringed sideroblasts (RARS); 24 with RA with excess blasts (RAEB); 5 with RAEB in transformation (RAEB-t); and 11 with acute myeloid leukemia transformed from MDS (AML-MDS). Levels of WT1 mRNA expression were assessed using the real-time quantitative polymerase chain reaction [Tamaki H, et al, Leukemia 1999]. WT1 mRNA levels increased with the aggressiveness of disease subtype (mean: RA, 220.9; RARS, 129.4; RAEB, 5,554.3; RAEB-t, 14,284.0; AML-MDS, 56,272.7 copies/μg) and with the aggressiveness of the International Prognostic Scoring System (IPSS) category (mean: low, 114.5; intermediate-1, 360.8; intermediate-2, 12,041.6; high, 7,357.9 copies/μg) in these patients. (2) IgG- and IgM-type anti-WT1 Ab titers were determined using the dot-blot assay [Elisseeva OA, Blood 2002] in sera from 45 of the 80 patients: 15 RA; 3 RARS; 18 RAEB; 3 RAEB-t; and 6 AML-MDS. IgM and IgG WT1 Abs were detected in 31 (79.5%) and 34 (87.2%) MDS patients, and 5 (83.3%) and 6 (100%) AML-MDS patients, respectively. WT1 Abs levels were not correlated with FAB subtype, IPSS, or WT1 mRNA expression in PBMCs. (3) When patients were divided into three groups based on the WT1 mRNA level (fewer than 100 copies/μg, 100 to 10,000 copies/μg, and more than 10,000 copies/μg), their survival rates differed significantly (P = 0.0186): survival was worse in those with increased WT1 mRNA levels. Specifically, a high WT1 mRNA level was a strong predictor of rapid AML transformation even if adjusted by the IPSS (P = 0.0005). Furthermore, patients with high levels of either IgM or IgG WT1 Abs had significantly better survival compared with those whose IgM and IgG WT1 Abs values were both low (P = 0.0007) even when adjusted by the IPSS (P = 0.0019). (CONCLUSIONS) This study showed for the first time that high WT1 mRNA expression and high WT1 Ab titers in PB affected the prognosis of MDS patients negatively and positively, respectively, suggesting that an optimal immune response against WT1 may beneficial. Recently, clinical trials of WT1 peptide-based immunotherapy have been conducted for various malignancies including MDS. Our data presented here may provide a rationale for anti-WT1 immunotherapy in MDS. Disclosures: No relevant conflicts of interest to declare.

Expression of the axon guidance protein Robo1 in pancreatic ductal adenocarcinoma from smokers compared to nonsmokers.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 305-305
Author(s):  
Lorraine A. Chantrill ◽  
Andreia Pinho ◽  
Jiamin Wu ◽  
Marc Giry-Latierre ◽  
Amanda Mawson ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Risk Factor ◽  
Protein Expression ◽  
Axon Guidance ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Interaction Analysis ◽  
Ductal Adenocarcinoma ◽  
Ductal Cells ◽  
Patient Consent ◽  
Never Smokers

305 Background: The most important modifiable risk factor for the development of pancreas cancer is smoking, which accounts for up to 25% of pancreatic ductal adenocarcinomas (PDAC; Maisonneuve P, Lowenfels AB: Epidemiology of pancreatic cancer: an update. Digestive Diseases 28:645-656, 2010), and the incidence of PDAC correlates with smoking prevalence (Weiss W, Benarde MA: The temporal relation between cigarette smoking and pancreatic cancer. American journal of public health 73:1403-1404, 1983). A recently published Ingenuity Pathway Analysis of GWAS genotype and risk factor data from the Pancreatic Cancer Case Control Consortium demonstrated that axon guidance signalling genes were significantly overrepresented in smokers (Tang H, Wei P, Duell EJ, et al: Axonal guidance signaling pathway interacting with smoking in modifying the risk of pancreatic cancer: A gene and pathway-based interaction analysis of GWAS data. Carcinogenesis:bgu010, 2014) and we aimed to investigate this link in our cohort. Methods: Tissue from resected PDAC were obtained from 200 patients via the Australian Pancreatic Cancer Genome Initiative with patient consent and ethical approval. Immunohistochemistry was performed on TMAs with the anti-Robo1 antibody (ab7279). The sections were scored on a 4-point scale of 0, 1, 2 and 3 intensity. All sections were scored blindly by two independent reviewers. Results: Robo1 protein expression is found in the normal pancreas, predominantly in acinar cells. In PDAC, Robo1 expression is predominantly in epithelial ductal cells. Most PDACs have Robo1 expression with an overall mean score of 1.65±0.05. 20 out of 200 patients were current smokers at the time of their pancreatectomy, 97 were never smokers, the remainder were ex-smokers. The mean score for smokers was 2.1± 0.1 and for never smokers 1.6±0.1 (p = 0.0003). Genomic analysis did not demonstrate any mutations in the Robo1 gene. There were 7 cases of loss of heterozygosity for Robo1; none of these were current smokers and they had an average score of 1.25±0.17. Conclusions: In addition to our genomic (Biankin AV, Waddell N, Kassahn KS, et al: Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes. Nature 491:399-405, 2012) and methylation data (Nones K, Waddell N, Song S, et al: Genome‐wide DNA methylation patterns in pancreatic ductal adenocarcinoma reveal epigenetic deregulation of SLIT‐ROBO, ITGA2 and MET signaling. International Journal of Cancer, 2014), we provide the results of protein expression of Robo1 in a clinically annotated cohort of 200 cases of PDAC. We demonstrate that patients who are currently smoking have enhanced Robo1 expression. Preliminary results indicate that this may confer a poorer prognosis when coupled with high SLIT2 expression.

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