Predictors Of Pancreatic Cancer Research Articles

Characterization of neuroendocrine regulation- and metabolism-associated molecular features and prognostic indicators with aid to clinical chemotherapy and immunotherapy of patients with pancreatic cancer.

The worldwide prevalence of pancreatic cancer has been rising in recent decades, and its prognosis has not improved much. The imbalance of substance and energy metabolism in tumour cells is among the primary causes of tumour formation and occurrence, which is often controlled by the neuroendocrine system. We applied Cox and LASSO regression analysis to develop a neuroendocrine regulation- and metabolism-related prognostic risk score model with three genes (GSK3B, IL18 and VEGFA) for pancreatic cancer. TCGA dataset served as the training and internal validation sets, and GSE28735, GSE62452 and GSE57495 were designated as external validation sets. Patients classified as the low-risk population (category, group) exhibited considerably improved survival duration in contrast with those classified as the high-risk population, as determined by the Kaplan-Meier curve. Then, we combined all the samples, and divided them into three clusters using unsupervised clustering analysis. Unsupervised clustering, t-distributed stochastic neighbor embedding (t-SNE), and principal component analysis (PCA) were further utilized to demonstrate the reliability of the prognostic model. Moreover, the risk score was shown to independently function as a predictor of pancreatic cancer in both univariate and multivariate Cox regression analyses. The results of gene set enrichment analysis (GSEA) illustrated that the low-risk population was predominantly enriched in immune-associated pathways. "ESTIMATE" algorithm, single-sample GSEA (ssGSEA) and the Tumor Immune Estimation Resource (TIMER) database showed immune infiltration ratings were enhanced in the low-risk category in contrast with the high-risk group. Tumour immune dysfunction and exclusion (TIDE) database predicted that immunotherapy for pancreatic cancer may be more successful in the high-risk than in the low-risk population. Mutation analysis illustrated a positive link between the tumour mutation burden and risk score. Drug sensitivity analysis identified 44 sensitive drugs in the high- and low-risk population. GSK3B expression was negatively correlated with Oxaliplatin, and IL18 expression was negatively correlated with Paclitaxel. Lastly, we analyzed and verified gene expression at RNA and protein levels based on GENPIA platform, HPA database and quantitative real-time PCR. In short, we developed a neuroendocrine regulation- and metabolism-associated prognostic model for pancreatic cancer that takes into account the immunological microenvironment and drug sensitivity.

Lymph Node Subcapsular Sinus Microenvironment-On-A-ChipModeling Shear Flow Relevant to Lymphatic Metastasis and Immune Cell Homing.

SummaryA lymph node sinus-on-a-chip adhesion microfluidic platform that recapitulates the hydrodynamic microenvironment of the lymph node subcapsular sinus was engineered. This device was used to interrogate the effects of lymph node remodeling on cellular adhesion in fluid flow relevant to lymphatic metastasis. Wall shear stress levels analytically estimated and modeled after quiescent and diseased/inflamed lymph nodes were experimentally recapitulated using a flow-based microfluidic perfusion system to assess the effects of physiological flow fields on human metastatic cancer cell adhesion. Results suggest that both altered fluid flow profiles and presentation of adhesive ligands, which are predicted to manifest within the lymph node subcapsular sinus as a result of inflammation-induced remodeling, and the presence of lymph-borne monocytic cells may synergistically contribute to the dynamic extent of cell adhesion in flow relevant to lymph node invasion by cancer and monocytic immune cells during lymphatic metastasis.

S0115 Analysis of Predictors of Pancreatic Cancer in an Endoscopic Ultrasound Registry of Patients With Suspected Intraductal Papillary Mucinous Cystic Neoplasm

S0115 Analysis of Predictors of Pancreatic Cancer in an Endoscopic Ultrasound Registry of Patients With Suspected Intraductal Papillary Mucinous Cystic Neoplasm

S0110 Chronic Pancreatitis Is the Main Predictor of Pancreatic Cancer in Young Adults in the U.S.

S0110 Chronic Pancreatitis Is the Main Predictor of Pancreatic Cancer in Young Adults in the U.S.

MicroRNA-221-3p is related to survival and promotes tumour progression in pancreatic cancer: a comprehensive study on functions and clinicopathological value

BackgroundThe microRNA miR-221-3p has previously been found to be an underlying biomarker of pancreatic cancer. However, the mechanisms of miR-221-3p underlying its role in pancreatic cancer pathogenesis, proliferation capability, invasion ability, drug resistance and apoptosis and the clinicopathological value of miR-221-3p have not been thoroughly studied.MethodsBased on microarray and miRNA-sequencing data extracted from Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), relevant literature, and real-time quantitative PCR (RT-qPCR), we explored clinicopathological features and the expression of miR-221-3p to determine its clinical effect in pancreatic cancer. Proliferation, migration, invasion, apoptosis and in vitro cytotoxicity tests were selected to examine the roles of mir-221-3p. In addition, several miR-221-3p functional analyses were conducted, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Protein–protein interaction (PPI) network analyses, to examine gene interactions with miR-221-3p.ResultsThe findings of integrated multi-analysis revealed higher miR-221-3p expression in pancreatic cancer tissues and blood than that in para-carcinoma samples (SMD of miR-221-3p: 1.52; 95% CI 0.96, 2.08). MiR-221-3p is related to survival both in pancreatic cancer and pancreatic ductal adenocarcinoma patients. Cell experiments demonstrated that miR-221-3p promotes pancreatic cancer cell proliferation capability, migration ability, invasion ability, and drug resistance but inhibits apoptosis. Further pancreatic cancer bioinformatics analyses projected 30 genes as the underlying targets of miR-221-3p. The genes were significantly distributed in diverse critical pathways, including microRNAs in cancer, viral carcinogenesis, and the PI3K-Akt signalling pathway. Additionally, PPI indicated four hub genes with threshold values of 5: KIT, CDKN1B, RUNX2, and BCL2L11. Moreover, cell studies showed that miR-221-3p can inhibit these four hub genes expression in pancreatic cancer.ConclusionsOur research revealed that pancreatic cancer expresses a high-level of miR-221-3p, indicating a potential miR-221-3p role as a prognosis predictor in pancreatic cancer. Moreover, miR-221-3p promotes proliferation capacity, migration ability, invasion ability, and drug resistance but inhibits apoptosis in pancreatic cancer. The function of miR-221-3p in the development of pancreatic cancer may be mediated by the inhibition of hub genes expression. All these results might provide an opportunity to extend the understanding of pancreatic cancer pathogenesis.

Lymph node ratio as valuable predictor in pancreatic cancer treated with R0 resection and adjuvant treatment

BackgroundLymph-node (LN) metastasis is an important prognostic factor in resected pancreatic cancer. In this study, the prognostic value of American Joint Committee on Cancer (AJCC) 8th edition N stage, lymph-node ratio (LNR), and log odds of positive lymph nodes (LODDS) in resected pancreatic cancer was investigated.MethodsBetween January 2005 and December 2017, there were 351 patients with pancreatic cancer treated with R0 resection and adjuvant therapy at Seoul National University Hospital. Relationships between the three LN parameters and overall survival (OS) and recurrence-free survival (RFS) were evaluated using a log-rank test and Cox proportional hazard regression model. Each multivariate-adjusted LN parameter was internally validated by bootstrap-corrected Harrell’s C-index.ResultsThe mean duration from surgery to adjuvant therapy was 47.6 ± 17.4 days. In total, the median OS and RFS was 31.7 (95% CI, 27.2-37.2) and 15.4 (95% CI, 13.5-17.7) months. The three LN classification systems were significantly correlated with OS and RFS in log-rank tests and multivariate-adjusted models (all p < 0.05). When internally validated, LNR showed the highest discrimination ability in predicting OS and RFS (each C–index = 0.65). LNR also showed the highest C-index in subgroup analysis, classified by adjuvant therapy modality. LNR and the AJCC 8th edition LN classification system were significantly associated with loco-regional recurrence (p = 0.026 and p = 0.027, respectively).ConclusionsLNR, which showed the best prognostic performance and significant relationship with loco-regional recurrence, can help further stratify the patients and establish an active treatment plan.

Predictors of underlying pancreatic cancer in patients with acute pancreatitis: a Danish nationwide cohort study

BackgroundTo identify demographic characteristics, comorbidities, medical procedures, and prescription drug use that may act as predictors of underlying pancreatic cancer in acute pancreatitis. MethodsA cohort study of all patients admitted to Danish hospitals with incident acute pancreatitis during 1999–2015. The ability of age, sex, selected comorbidities, medical procedures, and prescription drug use to predict underlying pancreatic cancer in acute pancreatitis (i.e., pancreatic cancer diagnosed up to one year after acute pancreatitis) was examined. The absolute risk and odds ratio (OR) with 95% confidence interval (CI) of cancer was computed for each variable. Results28,231 patients with incident acute pancreatitis, of which 283 (1.0%) had underlying pancreatic cancer, were included. Age >50 years was a predictor of pancreatic cancer with highest risk in patients aged 56–70 years. New-onset chronic pancreatitis (multivariable OR: 2.36 [95% CI: 1.35–4.14]) and new-onset diabetes (multivariable OR: 1.94 [95% CI: 1.30–2.92]) were also predictors of pancreatic cancer. Diagnoses of biliary or alcohol-related diseases were predictors of no underlying pancreatic cancer. Most variables examined had no or limited predictive ability. ConclusionAge, new-onset chronic pancreatitis, new-onset diabetes, and absence of biliary or alcohol-related diseases were predictors of underlying pancreatic cancer in acute pancreatitis patients.

Evaluation of fatty pancreas by proton density fat fraction using 3-T magnetic resonance imaging and its association with pancreatic cancer

PurposeTo evaluate whether pancreatic magnetic resonance imaging-proton density fat fraction (MRI-PDFF) correlates with histological pancreatic fat fraction and its possible usefulness as a biomarker of pancreatic cancer compared with pancreatic index (PI) using computed tomography (CT number of the pancreas divided by that of the spleen). MethodWe included 55 consecutive patients (24 with pancreatic cancer and 31 controls; median age, 72 years) who preoperatively underwent MRI-PDFF using IDEAL-IQ and unenhanced CT and did not receive preoperative therapy. Histologic pancreatic fat fraction was measured in non-tumorous pancreatic tissues at the resection stump. A board-certified radiologist evaluated MRI-PDFF and PI. Correlations were evaluated among MRI-PDFF, PI, and histologic pancreatic fat fraction; the usefulness of MRI-PDFF as a predictor of pancreatic cancer was assessed. ResultsHistologic pancreatic fat fraction significantly correlated with MRI-PDFF and PI (r = 0.802 and −0.534, respectively; P < 0.01). The absolute correlation coefficient was significantly higher for MRI-PDFF than for PI (P < 0.01). Compared with the control group, the pancreatic cancer group had higher MRI-PDFF and histologic pancreatic fat fraction (P < 0.01) but lower PI (P < 0.01). In multivariate analysis, MRI-PDFF was found to be the sole independent risk factor for pancreatic cancer (odds ratio: 1.19; P < 0.01). ConclusionsPancreatic fat, which was associated with pancreatic cancer, could be quantified by MRI-PDFF measurement; therefore, MRI-PDFF should be considered as a promising and superior imaging biomarker for estimating the probability of pancreatic cancer than PI.

Lymph Node Ratio as Valuable Predictor in Pancreatic Cancer Treated with R0 Resection and Adjuvant Treatment

Lymph Node Ratio as Valuable Predictor in Pancreatic Cancer Treated with R0 Resection and Adjuvant Treatment

Weight change and blood glucose concentration as markers for pancreatic cancer in subjects with new-onset diabetes mellitus: A matched case-control study

ObjectivesTo evaluate the potential of blood glucose levels and weight change before the onset of diabetes as predictors of pancreatic cancer among subjects with new-onset diabetes, that is, cancer-related diabetes versus normal type 2 diabetes. MethodsWe conducted a case-control study among subjects with new diabetes in the United Kingdom-based Clinical Practice Research Datalink. Cases were pancreatic cancer subjects with diabetes for ≤2 years before the cancer diagnosis (i.e., cancer-related diabetes). Controls were cancer-free, type 2 diabetic subjects matched to cases on age, sex, and diabetes duration. We calculated adjusted odds ratios (aORs) for pancreatic cancer as a function of both weight change and blood glucose before the onset of diabetes. ResultsWeight loss of 10.0%–14.9% at diabetes onset was associated with an aOR for pancreatic cancer of 3.58 (95% CI 2.31–5.54), loss of ≥15.0%, with an aOR of 4.56 (95% CI 2.82–7.36), compared with stable weight. Blood glucose levels of ≤5.1 mmol/L or 5.2–5.6 mmol/L before diabetes onset were associated with an increased risk of a pancreatic cancer diagnosis, with aORs of 2.42 (95% CI 1.60–3.66) and 2.20 (95% CI 1.45–3.35), respectively, when compared with blood glucose levels ≥6.3 mmol/L within >2–3 years before cancer detection. ConclusionsWeight loss as well as blood glucose levels in the normal range (and thus rapid development of hyperglycemia) before diabetes onset may be predictive of pancreatic cancer-related diabetes and may help target which subjects with new diabetes to refer for pancreatic cancer screening examinations.

Association Between Hepatitis B Infection and Pancreatic Cancer

The aim of this study was to assess the role of hepatitis B (HepB) infection in the causation of pancreatic cancer and the predictors of pancreatic cancer and mortality. We identified pancreatic cancer patients 11 to 70 years of age from the 2013-2014 National Inpatient Sample. Pearson χ test and Student's t-test were used for categorical and continuous variables, respectively. We assessed the association of HepB and pancreatic cancer and the independent mortality predictors by multivariate analyses. Of 69,210 pancreatic cancer patients, 175 patients with a history of HepB and 69,035 patients without a history of HepB were identified. Compared with the pancreatic cancer-non-HepB group, the pancreatic cancer-HepB group consisted more of younger (mean, 60.4 [standard deviation, 7.4] years vs 68.2 [standard deviation, 12.1] years), male, black, and Asian patients with low household income and nonelective admissions. The odds of developing pancreatic cancer among the HepB patients were significantly higher (adjusted odds ratio, 1.24; 95% confidence interval, 1.056-1.449; P = 0.008). Black race, age ≥ 65 years, and male sex demonstrated greater odds of mortality. This study concluded up to a 24% increased likelihood of pancreatic cancer among the HepB patients. Blacks showed greater odds of pancreatic cancer and related mortality.

Tu1353 - Predictors of Pancreatic Cancer Among Patients with Sentinel Episode of Acute Pancreatitis: A Large Population Based Study

Tu1353 - Predictors of Pancreatic Cancer Among Patients with Sentinel Episode of Acute Pancreatitis: A Large Population Based Study

Preoperative neutrophil-lymphocyte ratio as an independent prognostic predictor for pancreatic cancer

To evaluate the impact value of preoperative neutrophil-lymphocyte ratio (NLR) for the prognosis of pancreatic cancer patients. The clinical data of 65 patients with resectable pancreatic cancer were analyzed retrospectively. According to preoperative NLR, the patients were divided into high group (NLR ≥ 2.4) and low group (NLR < 2.4). Caner-specific survival was assessed using the Kaplan-Meier method. The 1-year survival rates and the clinic pathological factors in the two groups were analyzed using univariate analysis and COX regression model. The 1-year survival rate of higher NLR group and lower NLR group was 64.5% and 73.5% respectively, with statistic significance. A high NLR was identified as an independent risk factor of poorer prognosis for patients with pancreatic cancer (RR: 1.465; 95% CI: 1.078-1.993; P = 0.015). Preoperative NLR can be a clinically significant factor for the assessment of prognosis of Pancreatic Cancer.

Estrogen receptor expression in pancreas cancer - is there a future for hormonal therapy?

s / Pancreatology 14 (2014) S1eS129 S71 Background: Several studies have examined leukocyte telomere length (LTL) as a possible predictor for cancer at various organ sites. The hypothesis originallymotivatingmany of these studieswas that shorter telomereswould be associated with an increase in cancer risk, the results of epidemiologic studies have been inconsistent, however, and suggested positive, negative, or null associations. So far, only two studieshave addressed the associationof LTL in relation to pancreatic cancer risk and the results are contrasting. Aims: Our aim was to further our understanding on the relation between LTL and Pancreatic cancer risk. Patients & methods: We measured LTL in a prospective study of 331 pancreatic cancer cases and 331 controls in the context of the European Prospective Investigation into Cancer and Nutrition (EPIC). Results: We observed that the mean LTL was higher in cases (0.59±0.20) than in controls (0.57±0.17), although this difference was not statistically significant (p1⁄40.07), and a basic logistic regression model showed no association of LTL with pancreas cancer risk. When adjusting for levels of glycated hemoglobin and C-peptide, however, there was a weakly positive association between longer LTL and pancreatic cancer risk (for LTL as a continuous variable, OR1⁄41.13; 95% CI 1.01-1.27). Conclusion: Taken together, the results from our study do not support LTL as a uniform and strong predictor of pancreatic cancer but can provide insights into telomere dynamics.

Potential predictors of pancreatic cancer: A population-based screen.

164 Background: Pancreatic cancer (PC) is the fourth leading cause of cancer-related death in the U.S. Unfortunately, PC is usually diagnosed at late stages. We hypothesized that certain diagnoses may precede PC diagnosis and assist in early identification of pancreatic cancer patients. Methods: SEER-Medicare 1991-2005 was used to identify PC patients. PC and prePC diagnoses were identified using ICD9 codes. We then examined pre-pancreatic cancer (prePC) diagnoses and compared the frequency of those diagnoses by PC stage at time of cancer diagnosis. Stepwise logistic regression was used to assess potential PrePC diagnoses. Risk factors were compared by stage at diagnosis using Kruskal-Wallis test, stratified univariate analysis and logistic regression. Time to diagnosis was calculated for each PrePC diagnosis. Results: 19,801 PC patients were identified. Significant (p&lt;0.05) prePC diagnoses included acute pancreatitis, chronic pancreatitis, cyst/pseudocyst, other pancreatic disease, bile duct obstruction, diabetes, weight loss, jaundice, abdominal pain, hepatomegaly. Median time (months) and interquartile range percentiles (25th-75th) before PC diagnosis were as follows: acute pancreatitis 0.97 (0.33-8.6), chronic pancreatitis 1.56 (0.37-11), cyst/pseudocyst 0.83 (0.3-3.5), other pancreatic disease 0.47 (0.2-1.2), bile duct obstruction 0.4 (0.17- 0.83), diabetes 30.6 (11.3-59.8), weight loss 1.16 (0.43-5.1), jaundice 0.43 (0.2-0.8), abdominal pain 16 (1.07-55.5), hepatomegaly 1.06 (0.33-1.07). Patients diagnosed at AJCC stage 0 had a mean of 3.53 prePC diagnoses (±SD 1.42); stage IA, 2.80 (1.68); stage IB, 2.42 (1.57); stage IIA, 2.44 (1.63); stage IIB, 2.46 (1.64); stage III, 2.33 (1.59); and Stage IV, 1.79 (1.40) (p&lt;0.001). Conclusions: PC patients who presented at later stages were less likely to have prePC claims identified prior to PC diagnosis compared with patients diagnosed at earlier stages. This analysis of potential prePC diagnoses suggests that access to care and earlier identification of PC related conditions may factor into the stage at which this lethal disease is identified. Further studies need to be conducted to identify and analyze additional predictors of PC and better screen individuals at risk. No significant financial relationships to disclose.

An outcome predictor for pancreatic cancer?

An outcome predictor for pancreatic cancer?

Detection of RNA for the CCK-C receptor in peripheral blood: A predictor for pancreatic cancer

Detection of RNA for the CCK-C receptor in peripheral blood: A predictor for pancreatic cancer

Tumor angiogenesis as a prognostic predictor in pancreatic cancer.

The purpose of this study was to evaluate the role of angiogenesis, proliferative activity (assessed by Ki-67 expression), p53 and ras-oncogene (H-ras) expression, and conventional clinicopathologic factors in predicting overall survival rates in patients with pancreatic ductal adenocarcinoma. We followed-up 22 patients with ductal adenocarcinoma of the pancreas for a median of 19 months (range, 2 to 44 months). Angiogenesis was quantitated as vascular surface density (VSD) and the number of vessels per mm2 stroma (NVES) after microvessels were immunostained, using factor VIII-related antigen. p53, H-ras, and Ki-67 proteins were also determined immunohistochemically. VSD and NVES showed significant correlations with increased proliferative activity, poor tumor differentiation, and tumor size of 3 cm or more (P = 0.001, P = 0.013, and P = 0.047, respectively). The overall 2-year survival rate of 33.3% in patients with high VSD and NVES values was significantly worse than that of 66.6% estimated in patients with low microvessel count (log rank, 3.97; P = 0.046). In multivariate analysis using the Cox model, VSD was found to be an independent prognostic factor of survival (P = 0.039). H-ras and p53 expressions were not correlated with angiogenesis parameters. We conclude that, in pancreatic ductal adenocarcinoma, angiogenesis is closely related to tumor growth and patient survival.