Circulating Cell-Free DNA as a Potential Diagnostic Tool in Pancreatic Cancer: A Comparative Analysis

e16344 Background: Pancreatic cancer remains an aggressive and highly lethal disease, exhibiting an overall 5-year survival rate of merely 10%, among the lowest compared to other oncological conditions. The absence of early and effective diagnostic tools hampers the management of pancreatic cancer (PC) patients, leading to compromised quality of life and treatment outcomes. Liquid biopsies, a relatively novel diagnostic method, enable non-invasive sampling of tumor materials. Specific genetic information, particularly changes in circulating free DNA (cfDNA) levels, is believed to forecast poorer tumor differentiation, a more aggressive disease course, faster relapse, and potential use as an early cancer diagnostic marker or for evaluating treatment efficacy. Methods: This study was approved by the Kaunas Regional Bioethics Committee (Approval ID: BE-2-31). Patients with newly diagnosed and histologically confirmed PC, without prior treatment and patients with chronic pancreatitis (control group), admitted to the Department of Surgery at Lithuanian University of Health Sciences Hospital, Kaunas Clinics, between September 2022 and November 2023 were included in this study. Blood samples were obtained from the patients before any treatment procedures commenced. cfDNA was extracted from the collected blood using the QIAmp Circulating Nucleic Acid Kit (Qiagen). The concentration and quality of the extracted cfDNA were determined using the Qubit™ 1X dsDNA High Sensitivity (HS) and Broad Range (BR) Assay Kits (ThermoFisher Scientific, Inc., Waltham, MA, USA). Results: Throughout the study period, 55 patients were included (47 with PC and 8 with chronic pancreatitis). cfDNA levels exhibited significant elevation in PC patients compared to those with chronic pancreatitis (p = 0.037; median (minimum – maximum): 46.5 ng/ml (4 – 768) vs 21.9 ng/ml (8.56 – 138.4) accordingly). The determined cut-off value for cfDNA levels distinguishing PC from chronic pancreatitis was 23.65 ng/ml (Area Under the Curve (AUC) = 0.73, sensitivity = 0.851, specificity = 0.625. Nevertheless, no distinctions in cfDNA levels were noted concerning tumor localization, size, differentiation, spread, or survival rates. Conclusions: Liquid biopsies and alterations in cfDNA levels could aid in distinguishing pancreatic cancer from benign inflammatory diseases like chronic pancreatitis. Nonetheless, further studies and experiments are necessary for comprehensive validation.

The effective treatment of pancreatic cancer relies on the diagnosis of the disease at an early stage, a difficult challenge. One major obstacle in the development of diagnostic biomarkers of early pancreatic cancer has been the dual expression of potential biomarkers in both chronic pancreatitis and cancer. To better understand the limitations of potential protein biomarkers, we used ICAT technology and tandem mass spectrometry-based proteomics to systematically study protein expression in chronic pancreatitis. Among the 116 differentially expressed proteins identified in chronic pancreatitis, most biological processes were responses to wounding and inflammation, a finding consistent with the underlining inflammation and tissue repair associated with chronic pancreatitis. Furthermore 40% of the differentially expressed proteins identified in chronic pancreatitis have been implicated previously in pancreatic cancer, suggesting some commonality in protein expression between these two diseases. Biological network analysis further identified c-MYC as a common prominent regulatory protein in pancreatic cancer and chronic pancreatitis. Lastly five proteins were selected for validation by Western blot and immunohistochemistry. Annexin A2 and insulin-like growth factor-binding protein 2 were overexpressed in cancer but not in chronic pancreatitis, making them promising biomarker candidates for pancreatic cancer. In addition, our study validated that cathepsin D, integrin beta1, and plasminogen were overexpressed in both pancreatic cancer and chronic pancreatitis. The positive involvement of these proteins in chronic pancreatitis and pancreatic cancer will potentially lower the specificity of these proteins as biomarker candidates for pancreatic cancer. Altogether our study provides some insights into the molecular events in chronic pancreatitis that may lead to diverse strategies for diagnosis and treatment of these diseases.

e16302 Background: Approximately 80% of pancreatic ductal adenocarcinoma (PDAC) patients present with advanced disease at diagnosis, with a 5-year survival rate of less than 5%. According to molecular profiling, mutations in KRAS have been described in 90% of PDAC patients, and correlated with poor prognosis. Nevertheless, the invasiveness of tumor biopsy and the difficulties in obtaining quality samples in some patients remains a concern. Circulating free DNA (cfDNA) is considered a surrogate marker of tumor burden and may also act as a prognostic factor that can be used independently from tumor biopsy. In this study, we aim to explore molecular prognostic biomarkers using plasma samples. Methods: Patients with metastatic PDAC harboring KRAS mutation in tissue samples and treated with first-line chemotherapy were identified at Vall d’Hebron University Hospital. Clinical features and plasma samples were collected before starting any treatment. DNA mutations were analyzed in plasma and compared with tissue samples. In plasma, detection of KRAS mutation and total cfDNA concentration were evaluated for clinical significance. A cfDNA minimum 100 genome equivalent threshold was proposed based on results and utility. A Chi-square test was planned to prove the independence between cfDNA levels and KRAS detection in plasma. Survival analysis was performed using the Kaplan-Meier method. Results: We included 33 PDAC patients with a median age of 66.1 years old, 57% were women. All of them were treated with gemcitabine and Nab-paclitaxel. At the final analysis cut-off, 31 patients had died . KRAS mutation was detected in 25 patients’ blood samples (75.8%) and cfDNA-High levels were considered for 20 patients (60.6%). 19 of 20 (95%) patients with cfDNA-High correlated with KRAS blood detection, showing significant dependence (p-value 0.001). Median overall survival (OS) was 10.5 months in the KRAS detected group compared with 22.6 months in the KRAS non-detected group (HR for death 4.70; confidence interval (CI) 1.70-12.98, p-value 0.002). Better separation was seen using cfDNA where median OS was 9.8 months in the cfDNA-High group compared with 21.0 months in the cfDNA-Low group (HR for death 5.38; CI 2.17-13.31, p-value < 0.001). Conclusions: Liquid biopsy can provide quality prognostic information in metastatic PDAC patients. On account of this, the cfDNA level is proposed as a prognostic factor. However, prospective cohorts to validate this information are needed.[Table: see text]

Alcohol and cigarettes: Partners in crime in chronic pancreatitis

Desmoplasia of Pancreatic Ductal Adenocarcinoma

To estimate the levels of serum cytokines in chronic pancreatitis (CP) and pancreatic ductal adenocarcinoma (PDAC) patients in order to evaluate their usefulness as possible biomarkers. The study included 167 Caucasian patients: 74 with PDAC (28 men and 42 women, aged 30-88 years), 78 with CP (50 men and 21 women, aged 20-79 years) and 15 age-matched healthy controls hospitalized in the Department of Digestive Tract Diseases, Medical University of Lodz, Poland between 2006 and 2013. Serum MCP-1, transforming growth factor (TGF)-β1, HA and s-Fr were measured in patients with CP (n = 78), PDAC (n = 74) and healthy controls (n = 15) using ELISA (Corgenix United Kingdom Ltd R and D Systems). The severity of CP was assessed according to the Cambridge classification. Both patients with CP and PDAC had a significantly higher mean TGF-β1 serum level (1066 ± 582 and 888 ± 356 vs 264 ± 93, P < 0.0001), mean s-Fr (2.42 ± 1.385 and 2.41 ± 1.275 vs 0.6 ± 0.370, P < 0.0001) and mean HA (199 ± 254 and 270 ± 358 vs 40 ± 26, P < 0.0001) compared to controls. There was no difference in mean MCP-1 between all the groups. There were no significant differences in any cytokine levels between the PC and PDAC groups. No significant differences between serum cytokines depending on age, gender or smoking status were found in CP patients. Mean s-Fr concentration was significantly higher in CP, lasting longer than 5 years compared to those with a shorter disease clinical course (2.639 ± 1.125 vs 1.870 ± 0.970, P < 0.03). There was no correlation between tumor size, localization or TNM classification and serum TGF-β1, MCP-1, s-Fr and HA levels in patients with PDAC. No significant differences between cytokines depending on diabetes presence in CP were found. Nevertheless, mean serum TGF-β1 concentration in PDAC patients was higher in those with diabetes compared to the remaining group (986 vs 839, P = 0.043). Serum TGF-β1, s-Fr and HA may be considered additional diagnostic markers of CP and PDAC. TGF-β1 may be useful to predict endocrine insufficiency in PDAC.

Cell‐free circulating DNA (cfDNA), extracted by liquid biopsy, has been studied as a noninvasive biomarker for various diseases. The potential of cfDNA fragment size and level as a marker in lumbar canal stenosis (LCS) patients has never been studied. We investigated whether cfDNA is a biomarker of low back pain, leg pain, leg numbness severity in patients with an LCS. Blood samples were obtained from patients with LCS (n = 22) before and immediately after spinal surgery. Plasma DNA was isolated and examined for cfDNA fragment size and concentration. A cohort of healthy volunteers (n = 5) constituted the control group. The cfDNA fragment size tended to be shorter in patients than in healthy controls, but this difference was not significant (P = .186). cfDNA level was significantly higher in LCS patients (mean 0.614 ± 0.198 ng/μL, range 0.302‐1.150 ng/μL) than in healthy controls (mean 0.429 ± 0.064 ng/μL, range 0.366‐0.506 ng/μL) (P = .008). cfDNA level correlated positively with average pain (r = .435, P = .026) and leg numbness (r = .451, P = .018). cfDNA fragment size did not differ from before to after surgery, but cfDNA level increased postoperatively in patients with LCS. This was the first study investigating whether cfDNA fragment size and level are associated with pain in patients with LCS. Our findings suggest that cfDNA level may be an objective indicator of pain and surgical invasiveness in patients with LCS.

Molecular Analysis to Detect Pancreatic Ductal Adenocarcinoma in High-Risk Groups

Tumor-associated autoreactive antibodies could represent a moderately sensitive but highly specific type of biomarker. While autoantibodies in the blood of patients with pancreatic cancer have been reported, the consensus among studies is low and data validation is lacking. We profiled the abundance of circulating autoantibodies in patients with pancreatic ductal adenocarcinoma (PDAC) in a multi-step approach. For this purpose, microarrays with in situ expressed proteins were produced that contained 3060 non-mutated human proteins; one emphasis was on cell surface proteins. The microarrays were utilized for autoantibody screening of sera collected from patients of PDAC stages I, IIA, IIB/III and IV. In addition, samples were studied that represented the different grades of the precursor lesion intraductal pupillary mucinous neoplasm (IPMN) – low-grade, high-grade dysplasia and IPMN with associated carcinoma. Third, sera from patients diseased with the PDAC risk factor chronic pancreatitis (CP) as well as healthy donors served as control groups. The analysis revealed a significant increase in the overall proportion of immunoreactive proteins in late grades of IPMN and stages of PDAC; within each group, some sera displayed higher reactivity than others. The screening phase led to the identification of about 100 proteins, which showed a relatively high immunoreactivity associated with PDAC in comparison to an age- and sex-matched healthy control group. The characteristics of PDAC-associated autoantibodies were confirmed for the 100 proteins by analyzing sera from a total of 1200 PDAC, IPMN and CP patients as well as healthy donors. The patient groups were age- and sex-matched among each other. This confirmation phase validated the PDAC-related immunoreactivity of 17 proteins, showing high specificity of samples from PDAC patients in comparison to the healthy control group but low sensitivity of less than 10%. The clinically defined PDAC stages displayed different autoantibody profiles. However, no stage-related autoantibodies could be identified. Further, these PDAC-related antigens were also immunoreactive in smaller proportions of CP and IPMN patients, demonstrating the biological relation between PDAC and its precursors CP and IPMN. The majority of the other antigens showed a high immunoreactivity without correlation of autoantibody abundance and PDAC diagnosis, highlighting the importance of validation in large cohorts. The presence of autoantibodies specific for the 17 identified PDAC-related proteins is currently technically cross-validated by Luminex multiplex serology. In conclusion, the study has identified novel PDAC-related autoantibodies towards non-modified human proteins. While the specificity of some detected autoantibodies was high, the low sensitivity and the immunoreactivity of related precursor lesions make the definition of a broad applicable biomarker panel unlikely or too complex. However, the antigens that are specific for PDAC indicate target molecules, which could offer new therapeutic options in a personalized approach. Citation Format: Henning Boekhoff, Laura Hendricks, Elena Cairo, Andrea Bauer, Mari Hambardzumyan, Markus W. Büchler, Silvia Calderazzo, Vivienn Weru, Anette Kopp-Schneider, Hermann Brenner, Thilo Hackert, Oliver Strobel, Tim Waterboer, Nathalia Giese, Joerg D. Hoheisel. Profiling of circulating autoreactive antibodies in some 1200 patients with pancreatic ductal adenocarcinoma and progressive precursor lesions [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr A035.

Pancreatic ductal adenocarcinoma (PDAC) is by far the most common type of pancreatic cancer. It constitutes about 90% of tumors of the exocrine pancreas. The aggressive nature of PDAC along with a lack of diagnostic markers contributes to high lethality of this disease, which is nearly identical to its incidence. Studies from malignancies such as hepatocellular carcinoma and cervical cancer, along with the fact that liver and pancreas are in a close proximity, provided a plausible basis for the hypothesis of virus association in PDAC tumor development. However, there have been no established reports about virus(es) associated with pancreatic cancer. The present study identified a new cancer-associated virus in human PDAC samples, called Meleagrid herpesvirus-1 (MeHV-1), or also known commonly as herpesvirus of turkeys, by two different and independent approaches: experimental genomic subtraction and digital microRNAome subtraction between healthy and PDAC patients. In the first approach, a genome-wide experimental comparison of DNA from PDAC tissues to DNA from tissues of healthy individuals was performed by representational difference analysis (RDA). Using this technique, differences in sequence composition were selectively isolated and amplified with very high sensitivity. Virus sequences associated with the occurrence of pancreatic cancer were detected by this process. The second approach, performed in parallel, involved a sequence analysis of the complete microRNA (miRNA) content of PDAC tissue samples. The sequencing data was digitally compared to databases of human and viral sequences so as to identify viral miRNAs. Because of the limited number of molecules, this analysis form did not need any experimental selection and amplification in order to achieve a sufficiently enough sensitivity to find viral microRNAs. The common results of the two analyses strongly suggested that MeHV-1 plays a crucial role in PDAC tumor progression. One of the viral microRNAs – hvt-miR-H14-3p – was studied in detail at the functional level by both in vitro and in vivo experiments in order to define the molecular mechanism of action with regard to its effect on pancreatic tumor carcinogenesis. The key findings from this work include: 1. Identification of MeHV-1 DNA sequences in the PCR difference products (DPs) resulting from RDA on genomic DNA from PDAC and healthy tissues. 2. A tumor-specific MeHV-1 signature was also identified in the miRNA sequence analysis of tumor DNA, using an independent methodological approach. 3. RT-qPCR analyses showed that hvt-miR-H14-3p from MeHV-1 was expressed at significantly higher levels in PDAC and chronic pancreatitis (CP) tissues – CP being a chronic inflammation of the pancreas and a well-known risk factor of PDAC – than in healthy tissues. This observation was further verified using independent digital PCR platforms. 4. Metastatic and non-metastatic PDAC cell lines overexpressing hvt-miR-H14-3p showed a significant increase in migration and invasion compared to the respective controls, interestingly, without any significant change in proliferation. 5. Hvt-miR-H14-3p was found targeting cellular p27, down-regulating its expression. 6. The functional consequences of viral sequences identified in vitro could also be confirmed in vivo in NOD scid gamma mice. In conclusion, this study is very significant in elucidating functional consequences of viral sequences in PDAC for the definition of relevant molecular effects responsible for carcinogenesis.

Background/Aims: Patients with chronic pancreatitis (CP) have an increased risk of developing pancreatic cancer. The true incidence of pancreatic cancer in CP patients in South Korea remains unclear, and reliable methods for identifying patients with CP at increased risk for pancreatic cancer are still lacking. We aimed to present the incidence and risk factors of pancreatic cancer in a multicenter retrospective cohort of patients with CP. Methods: Patients with ICD-10 code for CP (K86.0, K86.1) who underwent abdominal CT or MRI between January 2010 and December 2021 in seven academic hospitals were retrospectively analyzed. Patients who did not have definite CP, had follow-up less than 1 year, and developed pancreatic cancer less than 1 year after diagnosis of CP were excluded. A standardized incidence ratio was demonstrated using the incidence of pancreatic cancer in all populations in South Korea. Risk factors of pancreatic cancer were determined in patients with CP using the Cox-proportional hazards model. Results: After exclusions, we identified 727 patients with definite CP with a median follow-up of 3.6 years. There were 588 (80.9%) males and 139 (19.1%) females (median age 56.5 years, range 18-93). During 3,290 person-years of observation, 16 pancreatic cancers (2.20%, 0.49% year) were diagnosed after a median follow-up of 2.4 years (range 1.4-6.5); 5 (31%) developed between 1 and 2 years, 4 (25%) between 2 and 3 years, 3 (19%) between 3 and 4 years, and 3 (25%) between 4-7 years. Age and sex-standardized incidence ratio of pancreatic cancer was 18.1 (95% CI 10.4-29.5). Patients with pancreatic cancer were older (p = 0.008), more experienced exacerbation of pancreatitis (p = 0.031), had less parenchymal calcification (p = 0.009), and had higher CA 19-9 levels (p &amp;lt; 0.001) compared to those without pancreatic cancer. Among 16 developed pancreatic cancers, underlying CPs were 10 (63%) chronic obstructive pancreatitis, 4 (25%) chronic obstructive and calcifying pancreatitis, 1 (6%) chronic calcifying pancreatitis, and 1 (6%) autoimmune pancreatitis. Factors associated with pancreatic cancer development included age (hazard ratio 4.830, 95% CI 1.556-14.99, p = 0.006), parenchymal calcification (hazard ratio 0.213, 95% CI 0.077-0.586, p = 0.003), pancreatic duct stricture (hazard ratio 2.706, 95% CI 1.007-7.271, p = 0.048), and CA 19-9 level (hazard ratio 22.49, 95% CI 6.272-80.67, p &amp;lt;0.001). By multivariable analysis, age (hazard ratio 5.580, 95% CI 1.604-19.41, p = 0.007) and CA 19-9 level (hazard ratio 25.56, 95% CI 7.022-93.06, p &amp;lt;0.001) were the independent risk factors for pancreatic cancer. Conclusions: Patients with CP have a high risk of developing pancreatic cancer in South Korea. High risks in CP patients with more 60-year age at CP diagnosis and high CA 19-9 level warrant careful surveillance for pancreatic cancer. Citation Format: Seunghwan Noh, Jae Hyuck Chang. Incidence and risk of pancreatic cancer in patients with chronic pancreatitis: define optimal subgroup for surveillance [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr A044.

ObjectivesNecroptosis, a programmed inflammatory cell death, is implicated in the pathogenesis of pancreatitis and its potential progression to pancreatic ductal adenocarcinoma (PDAC), but its role remains unclear. We compared plasma levels of necroptosis-related markers - mixed lineage kinase domain-like protein (MLKL), interleukin (IL)-33, and its soluble receptor (sST2)- in patients with chronic pancreatitis (CP), PDAC, and healthy controls (HC), to explore their diagnostic and prognostic significance. MethodsPlasma was collected from patients pre-procedurally (PDAC, n=82; CP, n=25) and from HC (n=39), and studied by ELISA. Clinical and routine laboratory data were collected, and pancreas was defined as soft or non-soft based on intraoperative or imaging findings. Mann-Whitney U test, Spearman correlation coefficients, ROC analysis were used for statistical analysis. ResultsPlasma MLKL was lower in patients with CP than in other groups (p<0.001) and PDAC patients treated with upfront surgery (PDACUS, n=65) had lower MLKL than HC (p=0.035). MLKL differentiated CP from PDACUS (AUC 0.83, p<0.001). sST2 levels were significantly lower in HC than in other groups (p<0.001) and in PDAC patients with a soft pancreas compared with non-soft (p<0.005). In Lewis antigen positive PDACUS (n=59), sST2 had positive correlations with CA19-9 measured concurrently and after 1 month, and with CEA measured after 1 or 6 months. ConclusionsCirculating levels of MLKL are lower in patients with CP than PDAC. Elevated sST2 levels are associated with pancreatic diseases. Further studies are required to show whether MLKL and sST2 could be useful biomarkers in evaluating pancreatic diseases.

We analyzed concentrations of osteopontin (OPN) in patients with pancreatic ductal adenocarcinoma (PDAC) in order to determine firstly whether it is useful to distinguish between PDAC patients and those with chronic non-hereditary pancreatitis (CP) and type 2 diabetes mellitus (T2DM), and secondly whether OPN concentrations depend on the PDAC stage. Groups consisting of 64 patients with PDAC, 71 with CP, 67 with T2DM and 48 healthy controls (CON) were enrolled in the study. Controls were compared with regard to levels of OPN, oxidative stress markers, conventional tumor markers and other biochemical parameters. Levels of OPN were higher in patients with PDAC compared with CP patients (P< 0.001), T2DM (P< 0.001) and CON (P< 0.001). There were increased OPN levels in CP patients in comparison with T2DM (P< 0.001) and CON (P< 0.001). Patients with PDAC in stage IV had higher OPN levels than PDAC patients in stage III (P< 0.01). There was no difference in OPN levels of PDAC patients in stage III compared to patients in stage II. Our pilot study demonstrates the usefulness of estimating OPN levels to differentiate between pancreatic cancer and chronic pancreatitis. Higher OPN levels over 102 ng/ml could be a potential diagnostic biomarker for pancreatic cancer.

Background:The study of changes in the microbiome in chronic pancreatitis (CP) and pancreatic ductal adenocarcinoma (PDAC) holds significant potential for developing noninvasive diagnostic tools as well as innovative interventions to alter the progression of diseases. This systematic review and meta-analysis aimed to analyze in detail the taxonomic and functional characteristics of the gut microbiome in patients with CP and PDAC.Methods:Two researchers conducted a systematic search across public databases to gather all published research up to June 2023. Diversity and gut microbiota composition are the main outcomes the authors focus on.Results:This meta-analysis included 14 studies, involving a total of 1511 individuals in the PDAC (n=285), CP (n=342), and control (n=649) groups. Our results show a significant difference in the composition of gut microbiota between PDAC/CP patients compared to healthy controls (HC), as evidenced by a slight decrease in α-diversity, including Shannon (SMD=−0.33; P=0.002 and SMD=−0.59; P<0.001, respectively) and a statistically significant β-diversity (P<0.05). The pooled results showed that at the phylum level, the proportion of Firmicutes was lower in PDAC and CP patients than in HC patients. At the genus level, more than two studies demonstrated that four genera were significantly increased in PDAC patients compared to HC (e.g. Escherichia-Shigella and Veillonella). CP patients had an increase in four genera (e.g. Escherichia-Shigella and Klebsiella) and a decrease in eight genera (e.g. Coprococcus and Bifidobacterium) compared to HC. Functional/metabolomics results from various studies also showed differences between PDAC/CP patients and HC. In addition, this study found no significant differences in gut microbiota between PDAC and CP patients.Conclusions:Current evidence suggests changes in gut microbiota is associated with PDAC/CP, commonly reflected by a reduction in beneficial species and an increase in the pathogenic species. Further studies are needed to confirm these findings and explore therapeutic possibilities.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by very poor prognosis. It is caused by asymptomatic course of the disease at early stage. Symptomatic PDAC means usually advanced stage of the disease, making radical treatment impossible. Finding of biological PDAC marker could improve PDAC treatment through early diagnosis. In our study, we investigated two adipokines: omentin and chemerin concentration in PDAC, chronic pancreatitis (CP) and healthy individuals. We examined 27 PDAC patients, 10 CP patients and 36 controls. To determine concentration of adipokines we used ELISA immunoenzymatic assay. Level of both adipokines was increased when comparing control group to PDAC patients. Additionally, chemerin concentration in CP group was elevated comparing to control. To evaluate both adipokines as potential PDAC biomarkers we performed ROC analysis. Chemerin (AUC = 0.913) displayed better discriminant ability than omentin-1 (AUC = 0.73). Some authors believe that chemerin may promote tumour growth by stimulating angiogenesis and is supposed to be a factor recruiting mesenchymal stroma cells (MSC) in tumour regions. Omentin-1 can inhibit tumourigenesis by TP53 stimulation. On the other hand, according to some studies, omentin-1 may promote cancer proliferation via Akt signalling pathway. Results from our study showed significantly elevated level of chemerin and omentin-1 in PDAC patients. Therefore, we believe that both investigated adipokines may provide promising and novel pharmacological insights for oncological diagnosis in the near future.