Serum IGFBP2 and MSLN As Diagnostic and Prognostic Biomarkers for Pancreatic Cancer

Overview

Journal HPB (Oxford)

Publisher Elsevier

Specialty Gastroenterology

Date 2013 Dec 7

PMID 24308545

Citations 35

Authors

Zachary W Kendrick

Matthew A Firpo

Robert C Repko

Courtney L Scaife

Douglas G Adler

Kenneth M Boucher

Sean J Mulvihill

Affiliations

Soon will be listed here.

Abstract

Background: Identification of diagnostic and prognostic biomarkers is a research priority for the improved management of pancreatic ductal adenocarcinoma (PDAC). Insulin-like growth factor binding protein 2 (IGFBP2) and mesothelin (MSLN) have shown potential as serum biomarkers in other cancers, but have not been adequately studied in PDAC.

Methods: Serum IGFBP2 and MSLN levels were quantified by enzyme-linked immunosorbent assay (ELISA) in a cohort of 84 PDAC patients, 84 healthy control subjects and 40 chronic pancreatitis (ChPT) patients. Regression models related IGFBP2 and MSLN levels to diagnosis, gender, age, stage and survival.

Results: IGFPB2 and MSLN serum levels were diagnostic for PDAC in age-adjusted models (P = 0.032 and P = 0.002, respectively) when compared with ChPT and healthy control samples. At a 95% specificity threshold, the sensitivity for IGFBP2 was 22% and the sensitivity for MSLN was 17%. Neither protein approached the diagnostic accuracy of CA 19-9. However, IGFBP2 or MSLN or both correctly identified 18 of the 28 samples misidentified by CA 19-9. In age-adjusted models, neither serum IGFBP2 (P = 0.36) nor MSLN (P = 0.29) were significant predictors of survival.

Discussion: Serum IGFBP2 and MSLN are weak diagnostic classifiers individually, but may be useful in a diagnostic biomarker panel.

Citing Articles

Mesothelin expression prediction in pancreatic cancer based on multimodal stochastic configuration networks.

Li J, Li X, Chen Y, Wang Y, Wang B, Zhang X Med Biol Eng Comput. 2024; .

PMID: 39641869 DOI: 10.1007/s11517-024-03253-2.

Prognostic and diagnostic value of circulating IGFBP2 in pancreatic cancer.

Xu J, Song Y, Zhou B, Yuan S, Gao S Open Med (Wars). 2024; 19(1):20230893.

PMID: 39221034 PMC: 11365464. DOI: 10.1515/med-2023-0893.

SVIP reduces IGFBP-2 expression and inhibits glioblastoma progression via stabilizing PTEN.

Wang Z, Qiao X, Chen Y, Peng N, Niu C, Wang Y Cell Death Discov. 2024; 10(1):362.

PMID: 39138166 PMC: 11322382. DOI: 10.1038/s41420-024-02130-z.

Mechanisms Underlying the Rarity of Skeletal Muscle Cancers.

Kump D Int J Mol Sci. 2024; 25(12).

PMID: 38928185 PMC: 11204341. DOI: 10.3390/ijms25126480.

Leucine rich repeat LGI family member 3: Integrative analyses support its prognostic association with pancreatic adenocarcinoma.

Yun H Medicine (Baltimore). 2024; 103(8):e37183.

PMID: 38394487 PMC: 11309673. DOI: 10.1097/MD.0000000000037183.

References

Poruk K, Gay D, Brown K, Mulvihill J, Boucher K, Scaife C . The clinical utility of CA 19-9 in pancreatic adenocarcinoma: diagnostic and prognostic updates. Curr Mol Med. 2013; 13(3):340-51. PMC: 4419808. DOI: 10.2174/1566524011313030003. View

Johnston F, Tan M, Tan Jr B, Porembka M, Brunt E, Linehan D . Circulating mesothelin protein and cellular antimesothelin immunity in patients with pancreatic cancer. Clin Cancer Res. 2009; 15(21):6511-8. PMC: 2782601. DOI: 10.1158/1078-0432.CCR-09-0565. View

Chen S, Hung W, Wang P, Paul C, Konstantopoulos K . Mesothelin binding to CA125/MUC16 promotes pancreatic cancer cell motility and invasion via MMP-7 activation. Sci Rep. 2013; 3:1870. PMC: 3660778. DOI: 10.1038/srep01870. View

Einama T, Homma S, Kamachi H, Kawamata F, Takahashi K, Takahashi N . Luminal membrane expression of mesothelin is a prominent poor prognostic factor for gastric cancer. Br J Cancer. 2012; 107(1):137-42. PMC: 3389425. DOI: 10.1038/bjc.2012.235. View

Harsha H, Kandasamy K, Ranganathan P, Rani S, Ramabadran S, Gollapudi S . A compendium of potential biomarkers of pancreatic cancer. PLoS Med. 2009; 6(4):e1000046. PMC: 2661257. DOI: 10.1371/journal.pmed.1000046. View

Compton C, Mulvihill S . Prognostic factors in pancreatic carcinoma. Surg Oncol Clin N Am. 1997; 6(3):533-54. View

Aktas B, Kasimir-Bauer S, Wimberger P, Kimmig R, Heubner M . Utility of mesothelin, L1CAM and Afamin as biomarkers in primary ovarian cancer. Anticancer Res. 2012; 33(1):329-36. View

Siegel R, Naishadham D, Jemal A . Cancer statistics, 2013. CA Cancer J Clin. 2013; 63(1):11-30. DOI: 10.3322/caac.21166. View

Chen R, Brentnall T, Pan S, Cooke K, White Moyes K, Lane Z . Quantitative proteomics analysis reveals that proteins differentially expressed in chronic pancreatitis are also frequently involved in pancreatic cancer. Mol Cell Proteomics. 2007; 6(8):1331-42. DOI: 10.1074/mcp.M700072-MCP200. View

10.

Servais E, Colovos C, Rodriguez L, Bograd A, Nitadori J, Sima C . Mesothelin overexpression promotes mesothelioma cell invasion and MMP-9 secretion in an orthotopic mouse model and in epithelioid pleural mesothelioma patients. Clin Cancer Res. 2012; 18(9):2478-89. PMC: 3759995. DOI: 10.1158/1078-0432.CCR-11-2614. View

11.

Zhang Y, Ying X, Han S, Wang J, Zhou X, Bai E . Autoantibodies against insulin-like growth factor‑binding protein-2 as a serological biomarker in the diagnosis of lung cancer. Int J Oncol. 2012; 42(1):93-100. PMC: 3583617. DOI: 10.3892/ijo.2012.1699. View

12.

Hassan R, Laszik Z, Lerner M, Raffeld M, Postier R, Brackett D . Mesothelin is overexpressed in pancreaticobiliary adenocarcinomas but not in normal pancreas and chronic pancreatitis. Am J Clin Pathol. 2006; 124(6):838-45. View

13.

Ren Y, Patel K, Paun B, Kern S . Structural analysis of the cancer-specific promoter in mesothelin and in other genes overexpressed in cancers. J Biol Chem. 2011; 286(14):11960-9. PMC: 3069398. DOI: 10.1074/jbc.M110.193458. View

14.

Deng L, Ke X, He Z, Yang D, Gong H, Zhang Y . A MSLN-targeted multifunctional nanoimmunoliposome for MRI and targeting therapy in pancreatic cancer. Int J Nanomedicine. 2012; 7:5053-65. PMC: 3449755. DOI: 10.2147/IJN.S34801. View

15.

Bharadwaj U, Li M, Chen C, Yao Q . Mesothelin-induced pancreatic cancer cell proliferation involves alteration of cyclin E via activation of signal transducer and activator of transcription protein 3. Mol Cancer Res. 2008; 6(11):1755-65. PMC: 2929833. DOI: 10.1158/1541-7786.MCR-08-0095. View

16.

Sharon E, Zhang J, Hollevoet K, Steinberg S, Pastan I, Onda M . Serum mesothelin and megakaryocyte potentiating factor in pancreatic and biliary cancers. Clin Chem Lab Med. 2011; 50(4):721-5. PMC: 6309905. DOI: 10.1515/CCLM.2011.816. View

17.

Showalter S, Huang Y, Witkiewicz A, Costantino C, Yeo C, Green J . Nanoparticulate delivery of diphtheria toxin DNA effectively kills Mesothelin expressing pancreatic cancer cells. Cancer Biol Ther. 2008; 7(10):1584-90. PMC: 3218426. DOI: 10.4161/cbt.7.10.6562. View

18.

Zhou Q, Mao Y, Jiang W, Chen Y, Huang R, Zhou X . Development of IGF signaling antibody arrays for the identification of hepatocellular carcinoma biomarkers. PLoS One. 2012; 7(10):e46851. PMC: 3469629. DOI: 10.1371/journal.pone.0046851. View

19.

Poruk K, Firpo M, Scaife C, Adler D, Emerson L, Boucher K . Serum osteopontin and tissue inhibitor of metalloproteinase 1 as diagnostic and prognostic biomarkers for pancreatic adenocarcinoma. Pancreas. 2013; 42(2):193-7. PMC: 3576824. DOI: 10.1097/MPA.0b013e31825e354d. View

20.

Argani P, Iacobuzio-Donahue C, Ryu B, Rosty C, Goggins M, Wilentz R . Mesothelin is overexpressed in the vast majority of ductal adenocarcinomas of the pancreas: identification of a new pancreatic cancer marker by serial analysis of gene expression (SAGE). Clin Cancer Res. 2001; 7(12):3862-8. View