Plasma KRAS as a biomarker for pancreatic ductal adenocarcinoma (PDAC).

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 316-316 ◽  
Author(s):  
Benjamin A. Krantz ◽  
Dana Tsui ◽  
Maeve Aine Lowery ◽  
Marinela Capanu ◽  
Kenneth H. Yu ◽  
...  
Keyword(s):  
Circulating Tumor Dna ◽  
Ductal Adenocarcinoma ◽  
Cancer Center ◽  
Peritoneal Disease ◽  
Kras Mutations ◽  
Factors Affecting ◽  
Droplet Pcr ◽  
Node Metastases ◽  
Predictive Assay

316 Background: PDAC needs validated diagnostic biomarkers for early detection and predictive markers for outcome. As 95% of PDACs harbor KRAS mutations (mKRAS), circulating tumor DNA (ctDNA) has potential utility in PDAC. We assessed the ability to detect and correlate mKRAS in a metastatic PDAC cohort from Memorial Sloan Kettering Cancer Center. Methods: 10 mL of whole blood was collected. cfDNA was extracted with QIAmp or QIAsymphony DNA extraction kits (Qiagen, Valencia, CA). Directed (KRAS G12D, G12R, G12V, Q61H) or multiplex (G12A, G12C, G12D, G12R, G12S, G12V, G13D) digital droplet PCR (ddPCR) was performed with Raindrop Plus (Raindance Technologies, Billerica, MA) or QX200 (BioRad, Hercules, CA) ddPCR systems. Number and size of liver, lung and lymph node metastases, peritoneal disease (mild, moderate, severe), ascites (trace, small, large) and bone mets (Y/N) were assessed by CT scan. Results: See table. 21 (55%) had detectable ctDNA (ctDNA(+)) with mean mutant allele fraction of 4.5% (0.015-36.8). ctDNA (+) vs (-) PFS and OS from collection were 6.9 and 8.4 months vs. 9.9 and 10.5 (p=0.89 for both). CA19-9, PFS and OS did not correlate with ctDNA tertile (p=0.15, 0.54 & 0.50). On treatment and disease activity were not associated with ctDNA status (p= 0.20 & 0.60). Number and size of liver mets were associated with ctDNA (+) (p=0.006 & 0.007). Conclusions: ctDNA KRAS detection was measurable in metastatic disease with rates consistent with other PDAC reports. Median PFS, OS were lower in ctDNA (+) group but not statistically significant in this diverse cohort. Number and size of liver metastases were significantly higher in ctDNA (+). Future study should focus on practice changing applications with standardized collection, intra-patient comparisons and role of liver disease burden. We have initiated studies to evaluate plasma KRAS prior to and during treatment to address its value as a predictive assay and explore factors affecting ctDNA detection. [Table: see text]

INVESTIGATION KRAS MUTATION IN CIRCULATION TUMOR DNA IN DIFFERENT STAGES OF COLORECTAL CANCER

2019 ◽  
Vol 65 (5) ◽  
pp. 701-707
Author(s):  
Vitaliy Shubin ◽  
Yuriy Shelygin ◽  
Sergey Achkasov ◽  
Yevgeniy Rybakov ◽  
Aleksey Ponomarenko ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Plasma Volume ◽  
Kras Mutation ◽  
Stage Iv ◽  
Circulating Tumor Dna ◽  
Stage Ii ◽  
Kras Gene ◽  
Kras Mutations ◽  
Droplet Pcr ◽  
Tumor Dna

To determine mutations in the plasma KRAS gene in patients with colorectal cancer was the aim of this study. The material was obtained from 44 patients with colorectal cancer of different stages (T1-4N0-2bM0-1c). Plasma for the presence of KRAS gene mutation in circulating tumor DNA was investigated using digital droplet polymerase chain reaction (PCR). KRAS mutations in circulating tumor DNA isolated from 1 ml of plasma were detected in 13 (30%) patients with cancer of different stages. Of these, with stage II, there were 3 patients, with III - 5 and with IV - 5. Patients who did not have mutations in 1 ml of plasma were analyzed for mutations of KRAS in circulating tumor DNA isolated from 3 ml of plasma. Five more patients with KRAS mutations were found with II and III stages. The highest concentrations of circulating tumor DNA with KRAS mutation were found in patients with stage IV. The increase in plasma volume to 3 ml did not lead to the identification of mutations in I stage. This study showed that digital droplet PCR allows identification of circulating tumor DNA with the KRAS mutations in patients with stage II-IV of colon cancer. The results can be used to determine the degree of aggressiveness of the tumor at different stages of the disease, but not the 1st, and it is recommended to use a plasma volume of at least 3 ml.

scholarly journals Ultra-low Input Circulating Tumor DNA Detection by MED-Amp in Early-Stage Pancreatic Cancer

2021 ◽  
Author(s):  
Erica D Pratt ◽  
David B Zhen ◽  
Robert W Cowan ◽  
Heather Cameron ◽  
Kara Schradle ◽  
...  
Keyword(s):  
Early Stage ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Circulating Tumor Dna ◽  
Fold Change ◽  
Diagnostic Sensitivity ◽  
Ductal Adenocarcinoma ◽  
Kras Mutations ◽  
The Relationship ◽  
Tumor Dna

Purpose: The clinical utility of circulating tumor DNA (ctDNA) has been shown in advanced pancreatic ductal adenocarcinoma (PDA). However, diagnostic sensitivity of many ctDNA assays is low in resectable and locally advanced disease, where tumor burden is substantially lower. We have previously described Multiplex Enrichment using Droplet Pre-Amplification (MED-Amp), a multiplexed panel for the detection of the most common oncogenic KRAS mutations in PDA. In this study, we aimed to assess the diagnostic sensitivity of MED-Amp for detection of rare mutant alleles present in the plasma of patients with localized PDA. Experimental Design: We retrospectively analyzed ninety-eight plasma samples from 51 patients with various stages of localized disease. For comparison, we measured ctDNA levels in 20 additional patients with metastatic PDA. The MED-Amp assay was used to measure the abundance of the four most common KRAS codon 12 mutations (G12C/D/R/V). We correlated the presence and quantity of ctDNA with overall survival (OS) as well as progression-free survival (PFS). Using serial plasma draws, we also assessed the relationship between changes in ctDNA allelic frequency and progression. Results: KRAS-positive ctDNA was detected in 52.9% of localized PDA and 75% of metastatic samples tested using DNA inputs as low as 2 ng. As previously reported, the presence of KRAS mutant ctDNA was correlated with worse OS for all disease stages (p = 0.02). In patients with localized PDA high ctDNA levels also correlated with significantly worse median OS (533 days vs 1090 days) and PFS (192 days vs 787 days). We also studied a small cohort of serial plasma draws to observe the relationship between ctDNA fold change and PFS. We found 83% of patients with increased fold change in mutant KRAS experienced disease progression (n=6). In contrast, 75% (n=4) of patients with decreased fold change remained disease-free (p=0.03). Conclusions: MED-Amp is a flexible and cost-effective approach for measurement of ctDNA in patients with localized cancer. Though this study focused on KRAS mutation detection, this assay could be adapted for a number of common oncogenic alterations.

Analysis of pancreatobiliary adenocarcinoma (PBC) treatment response and resistance utilizing circulating tumor DNA (ctDNA).

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 758-758
Author(s):  
Madhulika Banerjee ◽  
Alejandro Recio Boiles ◽  
Sumana Veeravelli ◽  
Jorge Andres Leiva ◽  
Kathylynn Saboda ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Target Genes ◽  
Circulating Tumor Dna ◽  
Ductal Adenocarcinoma ◽  
Driver Mutations ◽  
Resistance Mutations ◽  
Kras Mutations ◽  
Molecular Alterations ◽  
Imaging Results ◽  
Therapeutic Decision Making

758 Background: Accurate disease monitoring in PBC is instrumental for optimal therapeutic decision-making. CA 19-9 is the most utilized biomarker, though it has limited sensitivity/specificity and cannot be used in CA 19-9 non-secretors (n-S). ctDNA is a potentially helpful monitoring aid and surrogate for PBC n-S. Serial ctDNA could identify emerging resistant driver mutations. Our study prospectively examined ctDNA in PBC patients receiving treatment and retrospectively correlated it with clinical response. Methods: We performed genomic testing of ctDNA from metastatic PBC patients’ plasma from 11/2016 to 08/2019. This included 77 patients, of those, 18 had >1 ctDNA measurement with 49 correlative data points in total. Demographics, serial CA 19-9 levels and imaging results were collected. ctDNA analysis by parallel sequencing of amplified target genes (74) using Guardant360 was obtained. We correlated imaging and CA 19-9 responses with molecular alterations in patients receiving systemic chemotherapy. Descriptive statistics and logistic regression of the data was performed. Results: Of those included, median age was 66 yo, 50% male, and 92% pancreatic ductal adenocarcinoma. Baseline ctDNA showed 103 mutations including TP53 12.6%, KRAS 9.7%, MET 6.8%, APC, ARID1A and NF1 4.8% each, and others < 3%. 44% of patients were n-S with 75% having both TP53 and KRAS mutations. APC, ARID1A, and NF1 were only present in n-S. 91% vs 90% KRAS and 84% vs 78% TP53 of n-S and secretors (S), respectively, had correlation between ctDNA levels and imaging response. S TP53 and KRAS mutations correlated to CA19-9 levels and scans in 78% and 70% responses. New TP53 subclonal variant mutations were the most common resistance mutations for all progressions (75%). A logistic regression model of imaging progression on change in CA19-9 secretion and TP53 or KRAS expression was not statistically significant. Conclusions: Baseline ctDNA level changes ( TP53 and KRAS) can potentially act as a biomarker of response in PBC, specifically in n-S. TP53 subclonal mutations were the most common resistant alterations at progression and can be explored as future targets. This is being explored in larger prospective trials.

The impact of CDKN2A mutations on overall survival in pancreatic adenocarcinoma.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 278-278 ◽  
Author(s):  
Allison Doyle ◽  
Manfred M Kubler ◽  
Ashton C Harris ◽  
Alfredo López ◽  
Prateek Govindaraj ◽  
...  
Keyword(s):  
Overall Survival ◽  
Kinase Inhibitors ◽  
Single Gene ◽  
Stage Iv ◽  
Ductal Adenocarcinoma ◽  
Comprehensive Cancer Center ◽  
Cancer Center ◽  
Brca1 And Brca2 ◽  
Kras Mutations ◽  
The Impact

278 Background: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with a five-year survival rate of only 9%. Analyses based on tumor DNA mutations indicate the presence of specific molecular subtypes of PDAC. Tumor genomic profiling could result in better treatment selection and improved overall survival. We performed a single institution analysis of PDAC mutations and correlated them with clinical outcomes. Methods: PDAC samples from patients (pts) seen at the Lombardi Comprehensive Cancer Center between 2014 and 2018 were profiled using next generation sequencing including 592 whole-gene targets (Caris Life Sciences). Relevant clinical data was mined retrospectively and correlated with genomic data. Pt outcomes were correlated with the presence of mutations in KRAS, MSH2, MSH6, MLH1, PMS2, TP53, SMAD4, CDKN2A, BRCA1, and BRCA2. Results: Our cohort (N = 100) included 50% men and 50% women, 59% were Caucasian and 21% African-American. Thirty-two percent had stage II, 14% had stage III, and 38% had stage IV disease. Seventy-seven percent developed metastatic disease. Genetic mutations were found in KRAS 87% (N = 82), TP53 76% (N = 82), SMAD4 37% (N = 49), CDKN2A 29% (N = 66), and BRCA2 21% (N = 81). Sixty percent of pts with KRAS mutations also had TP53 mutations. Almost all pts with mutated SMAD4, CDKN2A, or BRCA2 also had mutated KRAS (89%, 84%, and 80%). Median overall survival (OS) for all pts from time of diagnosis was 31 months (m). Stratification of OS based on single gene mutations did not significantly impact OS except for CDKN2A. Patients with CDKN2A mutations had significantly reduced OS compared to wild type (22 m vs. 35 m; P = 0.018). OS based on presence of co-occurring mutations only showed a negative OS impact when CDKN2A mutations were present (14 m vs. 35 m; P = 0.021). Conclusions: Our data demonstrate that the presence of CDKN2A mutations is an independent negative prognostic OS indicator for patients with PDAC. This finding highlights the need to select PDAC pts for potential targeted therapies, including those that target the cell cycle pathway (e.g. cyclin-dependent kinase inhibitors).

Pilot study of plasma KRAS as a prognostic biomarker in localized pancreas ductal adenocarcinoma (PDAC).

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 294-294
Author(s):  
Benjamin A. Krantz ◽  
Erika Gedvilaite ◽  
Joanne F. Chou ◽  
Marinela Capanu ◽  
Daoqi You ◽  
...  
Keyword(s):  
Prospective Trial ◽  
Progression Free Survival ◽  
Predictive Marker ◽  
Disease Status ◽  
Ductal Adenocarcinoma ◽  
Kras Mutations ◽  
Free Survival ◽  
Risk Of Death ◽  
System Disease ◽  
Droplet Pcr

294 Background: Validated predictive and prognostic biomarkers are needed in PDAC. Such biomarkers could predict response and resistance early in treatment. As 95% of PDAC harbor KRAS mutations (mKRAS), plasma mKRAS has utility as a biomarker. We explored the prognostic value of mKRAS in a PDAC cohort at Memorial Sloan Kettering. Methods: 10 mL of whole blood was collected at diagnosis of localized PDAC and early interval CT scan (approx. 8 weeks). DNA was extracted with QIAamp DNA kits (Qiagen, Valencia, CA). Single locus, if tissue KRAS known, or multiplex (G12A, G12C, G12D, G12R, G12S, G12V, G13D) digital droplet PCR (ddPCR) was performed with QX200 (BioRad, Hercules, CA) ddPCR system. Disease status was determined by radiographic, CA19-9 and clinical evaluation. Results: N = 18 enrolled (median age: 65 [range 34-85]). Median time between baseline (B) and interval (I) blood was 2.53 months (range 0.9-6). One had locally recurrent disease, 2 AJCC stage IIa, 1 IIb and 14 III. Three had tissue KRAS G12D mutation, 6 G12V and 9 unknown. Eight had gemcitabine-based treatment, 10 5-FU-based and 5 radiation. See table. mKRAS and CA19-9 at B were not associated with progression free survival (PFS) or overall survival (OS). mKRAS detection at I was associated with shorter PFS/OS (P < 0.01), but CA19-9 was not. mKRAS change from B to I was also associated with PFS/OS. For every 1 copy/mL increase in the change of mKRAS from B to I, the risk of death or progression/death increased by nearly 2 fold after controlling for baseline value (p = 0.01 for OS, p = 0.03 for PFS). Four patients, all undetectable mKRAS at I, went to surgery; 2/4 resected. Conclusions: In this pilot, 59% of localized PDAC patients had detectable mKRAS at B. mKRAS detection at I and change from B to I were associated with PFS/OS supporting that mKRAS early in treatment may be a useful prognostic and predictive marker in localized PDAC. We have initiated a large prospective trial to evaluate the predictive and prognostic potential of plasma mKRAS in advanced PDAC. [Table: see text]

scholarly journals Circulating Tumor DNA Detection by Digital-Droplet PCR in Pancreatic Ductal Adenocarcinoma: A Systematic Review

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 994
Author(s):  
Marisol Huerta ◽  
Susana Roselló ◽  
Luis Sabater ◽  
Ana Ferrer ◽  
Noelia Tarazona ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Residual Disease ◽  
Malignant Tumors ◽  
Circulating Tumor Dna ◽  
Ductal Adenocarcinoma ◽  
Epigenetic Alterations ◽  
Non Invasive ◽  
Droplet Pcr ◽  
Tumor Dna

Pancreatic cancer (PC) is one of the most devastating malignant tumors, being the seventh leading cause of cancer-related death worldwide. Researchers and clinicians are endeavoring to develop strategies for the early detection of the disease and the improvement of treatment results. Adequate biopsy is still challenging because of the pancreas’s poor anatomic location. Recently, circulating tumor DNA (ctDNA) could be identified as a liquid biopsy tool with huge potential as a non-invasive biomarker in early diagnosis, prognosis and management of PC. ctDNA is released from apoptotic and necrotic cancer cells, as well as from living tumor cells and even circulating tumor cells, and it can reveal genetic and epigenetic alterations with tumor-specific and individual mutation and methylation profiles. However, ctDNA sensibility remains a limitation and the accuracy of ctDNA as a biomarker for PC is relatively low and cannot be currently used as a screening or diagnostic tool. Increasing evidence suggests that ctDNA is an interesting biomarker for predictive or prognosis studies, evaluating minimal residual disease, longitudinal follow-up and treatment management. Promising results have been published and therefore the objective of our review is to understand the current role and the future perspectives of ctDNA in PC.

scholarly journals Multiplex Enrichment and Detection of Rare KRAS Mutations in Liquid Biopsy Samples using Digital Droplet Pre-Amplification

2018 ◽  
Author(s):  
Erica D. Pratt ◽  
Robert W. Cowan ◽  
Sara L. Manning ◽  
Edmund Qiao ◽  
Heather Cameron ◽  
...  
Keyword(s):  
Single Molecule ◽  
Liquid Biopsy ◽  
High Sensitivity ◽  
Circulating Tumor Dna ◽  
Tumor Burden ◽  
Allelic Frequency ◽  
Cancer Surveillance ◽  
Ductal Adenocarcinoma ◽  
Kras Mutations ◽  
Oncology Research

AbstractOncology research is increasingly incorporating molecular detection of circulating tumor DNA (ctDNA) as a tool for cancer surveillance and early detection. However, non-invasive monitoring of conditions with low tumor burden remains challenging, as the diagnostic sensitivity of most ctDNA assays is inversely correlated with total DNA concentration and ctDNA abundance. Here we present the Multiplex Enrichment using Droplet Pre-Amplification (MED-Amp) method, which com-bines single-molecule emulsification and short-round PCR preamplification with digital droplet PCR (ddPCR) detection of mutant DNA template. The MED-Amp assay increased mutant signal by over 50-fold with minimal distortion in allelic frequency. We demonstrate detection of as few as 3 mutant copies in wild-type DNA concentrations ranging from 5 to 50ng. The MED-Amp assay successfully detected KRAS mutant ctDNA in 86% plasma samples obtained from patients with metastatic pancreatic ductal adenocarcinoma. This assay for high-sensitivity rare variant detection is appropriate for liquid biopsy samples, or other limited clinical biospecimens

Clinical utility of circulating tumor DNA (ctDNA) in resectable pancreatic ductal adenocarcinoma (PDAC).

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 247-247
Author(s):  
Hui-Li Wong ◽  
Kevin Bushell ◽  
Joanna Karasinska ◽  
Sarah Arthur ◽  
Ryan Morin ◽  
...  
Keyword(s):  
Clinical Utility ◽  
Residual Disease ◽  
Hot Spot ◽  
Circulating Tumor Dna ◽  
Ductal Adenocarcinoma ◽  
Plasma Samples ◽  
Kras Mutations ◽  
Low Sensitivity ◽  
Monitoring Treatment

247 Background: ctDNA is emerging as a promising biomarker, with potential utility in screening, detecting minimal residual disease after curative resection and monitoring treatment response or resistance in advanced disease. Most PDAC studies to date have focused on identifying mutant KRAS ctDNA in metastatic disease. Here we perform sequential ctDNA quantification in patients (pts) with resectable PDAC using a novel and highly sensitive multiplex technology to explore the clinical utility of ctDNA as a diagnostic and prognostic biomarker. Methods: Banked plasma and tumor samples from 18 pts with resected PDAC were retrieved. Plasma samples were collected 0-28 days before, and 28-70 days after surgery. DNA was extracted using standard protocols and analyzed using the OnTarget system, which enriches for DNA molecules containing hot spot mutations prior to sequencing. A 96-plex panel that includes the most prevalent mutations in KRAS, PIK3CA and TP53 was used. Results: 16 pts (89%) had at least 1 mutation detected by OnTarget in the tumor sample, most frequently in KRAS codon 12 (n = 14). ctDNA was detected in the pre-operative blood sample in 7/16 pts with tumor mutations (sensitivity 44%) and 0/2 pts without detectable tumor mutations (specificity 100%). Of the 10 pts with available post-operative blood samples, 1 did not have a tumor mutation. 4 pts had detectable ctDNA, 3 of whom have recurred. In contrast, 0 of the 5 pts without detectable post-operative ctDNA have recurred. At median follow-up of 37 weeks, recurrence-free survival (RFS) was significantly longer in pts without detectable ctDNA after surgery (median not reached vs 9 weeks, p = 0.022). Of 11 plasma samples with detectable ctDNA, 3 harbored mutations that were not detected in the primary tumor, including 2 non-KRAS mutations (GNAS R201H and PIK3CA E542K). Conclusions: Pre-operative ctDNA has low sensitivity, suggesting limited utility in PDAC screening. RFS was significantly longer in pts without detectable post-operative ctDNA; however this analysis is limited by small numbers and short follow-up. Discordance in hot spot mutations detected in tumor and matched plasma was observed in 27% of samples, possibly related to intratumoral heterogeneity.

A blood-based assay for diagnosis of early-stage pancreatic cancer.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 234-234
Author(s):  
Thomas Jens Ettrich ◽  
Andreas Wolfgang Berger ◽  
Daniel Schwerdel ◽  
Anke C. Reinacher-Schick ◽  
Waldemar Uhl ◽  
...  
Keyword(s):  
Early Stage ◽  
Circulating Tumor Dna ◽  
Pancreatic Disease ◽  
Stage I ◽  
Ductal Adenocarcinoma ◽  
C Statistic ◽  
Dismal Prognosis ◽  
Marker Combination ◽  
Droplet Pcr ◽  
Ctdna Analysis

234 Background: Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis. Biomarker are needed to facilitate early and preferably noninvasive detection of PDAC, which directly may influence patients’ prognosis. Here we aimed to test a new biomarker combination for early PDAC, consisting of thrombospondin-2 (THBS2), CA19-9 and circulating tumor DNA (ctDNA) analysis. Methods: Thirty-nine patients with histologically proven and clearly resectable PDAC (recruited from the NEONAX trial, NCT02047513) were enrolled. Fifteen patients with benign pancreatic disease (intraductal papillary-mucinous neoplasms, IPMN) served as controls. Blood samples were collected prior treatment. KRAS genotyping was performed after isolation of ctDNA from plasma (QIAamp MinElute ccfDNA Kit, Qiagen) by digital droplet PCR ( KRAS Screening Multiplex Kit; QX200 system, both: Bio-Rad). Clinical data and CA 19-9 levels were assessed by ELISA (Roche); THBS2 values were determined by Quantikine ELISA Human Thrombospondin-2 (R&D Systems). Statistical analyses were done by using GraphPad Prism Version 7.00, GraphPad Software, Inc. Results: THBS2 had a c-statistic of 0.73 for all PDAC stages which was comparable to that of CA 19-9 (0.78). The c-statistic was improved to 0.94 by combining CA 19-9, THBS2 and total cfDNA amount. This marker combination performed best for all stages. C-statistics of defined PDAC stages was 0.93, 1.00 and 0.92 for stage I, stage II and stage III, respectively. Of note, the biggest improvement in sensitivity and specificity was seen for stage I PDAC. Here, c-statistic improved from 0.69 or 0.85 for CA 19-9 alone or the combination of CA 19-9 and THBS2, respectively, to 0.93 for the three-marker combination. Conclusions: These data underscore that CA 19-9, THBS2 and cfDNA marker combination constitutes a composite liquid biomarker for non-invasive diagnosis of early-stage PDAC with a remarkable specificity. Larger studies are needed to examine the power of this approach.

scholarly journals Serum  JAK/STAT profile is related to the IL expression but not with the outcome in pancreatic adenocarcinoma patients

2021 ◽  
Vol 67 (3) ◽  
pp. 107-112
Author(s):  
Livia Petrusel ◽  
Maria Ilies ◽  
Daniel Leucuta ◽  
Ioana Rusu ◽  
Andrada Seicean ◽  
...  
Keyword(s):  
Cox Regression ◽  
Serum Levels ◽  
Ductal Adenocarcinoma ◽  
Analysis Model ◽  
Inflammatory Status ◽  
Metastasis Development ◽  
Node Metastases ◽  
Stat Pathway

Current genetic characterization of pancreatic ductal adenocarcinoma (PDAC) does not integrate the host reaction to cancer cells and cannot predict the response to chemo- or immunotherapy. The JAK/STAT pathway is an important factor of cytokine-mediated cancer inflammation, but its relationship with pancreatic carcinogenesis and the role of potential biomarkers is not established yet. Our study aimed to assess the significance of serum levels of JAK/STAT3 expression and inflammatory cytokines in PDAC in relation to the clinicopathological features and prognosis. This prospective cohort study included patients with proven adenocarcinoma and a matched group of controls without any malignancies. There were evaluated the serum expression of IL2, 6, 8, 17, JAK2, and STAT3 by ELISA assays in these two groups. The PDAC patients were followed up for 24 months. A Cox regression multivariate analysis model was used to determine factors influencing survival. The study comprised 56 patients with PDAC and 56 controls. The upregulated serum JAK2/STAT3 or cytokines were present in about half of the patients with PDAC, similar to controls. The expression of JAK2 in serum of PDAC patients was significantly associated with the expression of IL2 (p=0.03) and IL6 (p=0.02) but not with survival or metastasis development. Only age and the presence of lymph node metastases were associated with reduced survival in multivariate analyses. The STAT 3/JAK2 expression, although correlated with inflammatory status (IL2, IL6) was not overexpressed in PDAC compared to controls and proved no prognostic value.

Sign in / Sign up

Export Citation Format

Share Document