Serum Metabolite Biomarkers for Pancreatic Tumors: Neuroendocrine and Pancreatic Ductal Adenocarcinomas-A Preliminary Study

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2023 Jun 28

PMID 37370852

Authors

Karolina Skubisz

Krzysztof Dabkowski

Emilia Samborowska

Teresa Starzynska

Anna Deskur

Filip Ambrozkiewicz

Jakub Karczmarski

Mariusz Radkiewicz

Katarzyna Kusnierz

Beata Kos-Kudla

Tadeusz Sulikowski

Patrycja Cybula

Agnieszka Paziewska

Affiliations

Soon will be listed here.

Abstract

Background: Pancreatic cancer is the most common pancreatic solid malignancy with an aggressive clinical course and low survival rate. There are a limited number of reliable prognostic biomarkers and a need to understand the pathogenesis of pancreatic tumors; neuroendocrine (PNET) and pancreatic ductal adenocarcinomas (PDAC) encouraged us to analyze the serum metabolome of pancreatic tumors and disturbances in the metabolism of PDAC and PNET.

Methods: Using the AbsoluteIDQ p180 kit (Biocrates Life Sciences AG, Innsbruck, Austria) with liquid chromatography-mass spectrometry (LC-MS), we identified changes in metabolite profiles and disrupted metabolic pathways serum of NET and PDAC patients.

Results: The concentration of six metabolites showed statistically significant differences between the control group and PDAC patients ( < 0.05). Glutamine (Gln), acetylcarnitine (C2), and citrulline (Cit) presented a lower concentration in the serum of PDAC patients, while phosphatidylcholine aa C32:0 (PC aa C32:0), sphingomyelin C26:1 (SM C26:1), and glutamic acid (Glu) achieved higher concentrations compared to serum samples from healthy individuals. Five of the tested metabolites: C2 (FC = 8.67), and serotonin (FC = 2.68) reached higher concentration values in the PNET serum samples compared to PDAC, while phosphatidylcholine aa C34:1 (PC aa C34:1) (FC = -1.46 (0.68)) had a higher concentration in the PDAC samples. The area under the curves (AUC) of the receiver operating characteristic (ROC) curves presented diagnostic power to discriminate pancreatic tumor patients, which were highest for acylcarnitines: C2 with AUC = 0.93, serotonin with AUC = 0.85, and PC aa C34:1 with AUC = 0.86.

Conclusions: The observations presented provide better insight into the metabolism of pancreatic tumors, and improve the diagnosis and classification of tumors. Serum-circulating metabolites can be easily monitored without invasive procedures and show the present clinical patients' condition, helping with pharmacological treatment or dietary strategies.

Citing Articles

Diagnostics and Therapy for Malignant Tumors.

Tsai C, Wang C, Chang H, Chang P, Chang C, Chu T Biomedicines. 2025; 12(12.

PMID: 39767566 PMC: 11726849. DOI: 10.3390/biomedicines12122659.

References

Guadagno E, DAvella E, Cappabianca P, Colao A, Del Basso De Caro M . Ki67 in endocrine neoplasms: to count or not to count, this is the question! A systematic review from the English language literature. J Endocrinol Invest. 2020; 43(10):1429-1445. DOI: 10.1007/s40618-020-01275-9. View

Chen L, Zhang C, Gui Q, Chen Y, Yang Y . Ultra‑performance liquid chromatography coupled with quadrupole time‑of‑flight mass spectrometry‑based metabolic profiling of human serum prior to and following radical resection of colorectal carcinoma. Mol Med Rep. 2015; 12(5):6879-86. DOI: 10.3892/mmr.2015.4289. View

Askarpour M, Hadi A, Miraghajani M, Symonds M, Sheikhi A, Ghaedi E . Beneficial effects of l-carnitine supplementation for weight management in overweight and obese adults: An updated systematic review and dose-response meta-analysis of randomized controlled trials. Pharmacol Res. 2019; 151:104554. DOI: 10.1016/j.phrs.2019.104554. View

Hall Z, Chiarugi D, Charidemou E, Leslie J, Scott E, Pellegrinet L . Lipid Remodeling in Hepatocyte Proliferation and Hepatocellular Carcinoma. Hepatology. 2020; 73(3):1028-1044. DOI: 10.1002/hep.31391. View

Balakrishna P, George S, Hatoum H, Mukherjee S . Serotonin Pathway in Cancer. Int J Mol Sci. 2021; 22(3). PMC: 7865972. DOI: 10.3390/ijms22031268. View

Li Z, Guan M, Lin Y, Cui X, Zhang Y, Zhao Z . Aberrant Lipid Metabolism in Hepatocellular Carcinoma Revealed by Liver Lipidomics. Int J Mol Sci. 2017; 18(12). PMC: 5751153. DOI: 10.3390/ijms18122550. View

Wang W, Cui J, Ma H, Lu W, Huang J . Targeting Pyrimidine Metabolism in the Era of Precision Cancer Medicine. Front Oncol. 2021; 11:684961. PMC: 8194085. DOI: 10.3389/fonc.2021.684961. View

Takagi A, Hawke P, Tokuda S, Toda T, Higashizono K, Nagai E . Serum carnitine as a biomarker of sarcopenia and nutritional status in preoperative gastrointestinal cancer patients. J Cachexia Sarcopenia Muscle. 2021; 13(1):287-295. PMC: 8818668. DOI: 10.1002/jcsm.12906. View

Abdel-Razik A, Elhelaly R, Elzehery R, El-Diasty A, Abed S, Elhammady D . Could serotonin be a potential marker for hepatocellular carcinoma? A prospective single-center observational study. Eur J Gastroenterol Hepatol. 2016; 28(5):599-605. DOI: 10.1097/MEG.0000000000000569. View

10.

Arutla M, Raghunath M, Deepika G, Jakkampudi A, Murthy H, Rao G . Efficacy of enteral glutamine supplementation in patients with severe and predicted severe acute pancreatitis- A randomized controlled trial. Indian J Gastroenterol. 2019; 38(4):338-347. DOI: 10.1007/s12664-019-00962-7. View

11.

Hou G, Ding D, Tian T, Dong W, Sun D, Liu G . Metabolomics-based classification reveals subtypes of hepatocellular carcinoma. Mol Carcinog. 2022; 61(11):989-1001. DOI: 10.1002/mc.23455. View

12.

Khin P, Po W, Thein W, Sohn U . Apoptotic effect of fluoxetine through the endoplasmic reticulum stress pathway in the human gastric cancer cell line AGS. Naunyn Schmiedebergs Arch Pharmacol. 2019; 393(4):537-549. DOI: 10.1007/s00210-019-01739-7. View

13.

Yu L, Zeng Z, Tan H, Feng Q, Zhou Q, Hu J . Significant metabolic alterations in patients with hepatitis B virus replication observed via serum untargeted metabolomics shed new light on hepatitis B virus infection. J Drug Target. 2021; 30(4):442-449. DOI: 10.1080/1061186X.2021.2009841. View

14.

Jin X, Li H, Li B, Zhang C, He Y . Knockdown and inhibition of hydroxytryptamine receptor 1D suppress proliferation and migration of gastric cancer cells. Biochem Biophys Res Commun. 2022; 620:143-149. DOI: 10.1016/j.bbrc.2022.06.088. View

15.

Elmallah M, Ortega-Deballon P, Hermite L, Pais-de-Barros J, Gobbo J, Garrido C . Lipidomic profiling of exosomes from colorectal cancer cells and patients reveals potential biomarkers. Mol Oncol. 2022; 16(14):2710-2718. PMC: 9298677. DOI: 10.1002/1878-0261.13223. View

16.

Chang X, Liu X, Wang H, Yang X, Gu Y . Glycolysis in the progression of pancreatic cancer. Am J Cancer Res. 2022; 12(2):861-872. PMC: 8900001. View

17.

Zou L, Guo L, Zhu C, Lai Z, Li Z, Yang A . Serum phospholipids are potential biomarkers for the early diagnosis of gastric cancer. Clin Chim Acta. 2021; 519:276-284. DOI: 10.1016/j.cca.2021.05.002. View

18.

Choi S, Yoo Y, Kim H, Lee H, Chung H, Nam M . Clinical and biochemical relevance of monounsaturated fatty acid metabolism targeting strategy for cancer stem cell elimination in colon cancer. Biochem Biophys Res Commun. 2019; 519(1):100-105. DOI: 10.1016/j.bbrc.2019.08.137. View

19.

Alexandraki K, Spyroglou A, Kykalos S, Daskalakis K, Kyriakopoulos G, Sotiropoulos G . Changing biological behaviour of NETs during the evolution of the disease: progress on progression. Endocr Relat Cancer. 2021; 28(5):R121-R140. DOI: 10.1530/ERC-20-0473. View

20.

Niu Q, Li L, Zhang C, Qi C, He Q, Zhu Y . Expression of 5-HT Relates to Stem Cell Marker LGR5 in Patients with Gastritis and Gastric Cancer. Dig Dis Sci. 2022; 68(5):1864-1872. PMC: 10133054. DOI: 10.1007/s10620-022-07772-6. View