β6-Integrin Serves as a Potential Serum Marker for Diagnosis and Prognosis of Pancreatic Adenocarcinoma.
Journal
Clinical and translational gastroenterology
ISSN: 2155-384X
Titre abrégé: Clin Transl Gastroenterol
Pays: United States
ID NLM: 101532142
Informations de publication
Date de publication:
13 08 2021
13 08 2021
Historique:
received:
07
04
2021
accepted:
12
07
2021
entrez:
13
8
2021
pubmed:
14
8
2021
medline:
19
1
2022
Statut:
epublish
Résumé
Despite enormous efforts during the past decades, pancreatic adenocarcinoma (PAC) remains one of the most deleterious cancer entities. A useful biomarker for early detection or prognosis of PAC does not yet exist. The goal of our study was the characterization of β6-integrin (ITGB6) as a novel serum tumor marker for refined diagnosis and prognosis of PAC. Serum ITGB6 levels were analyzed in 3 independent PAC cohorts consisting of retrospectively and prospectively collected serum and/or (metastatic) PAC tissue specimens. Using 2 independent cohorts, we measured serum ITGB6 concentrations in 10 chronic pancreatitis patients, 10 controls, as well as in 27 (cohort 1) and 24 (cohort 2) patients with PAC, respectively. In these patients, we investigated whether ITGB6 serum levels correlate with known clinical and prognostic markers for PAC and whether they might differ between patients with PAC or benign inflammatory diseases of the pancreas. We found that elevated serum ITGB6 levels (≥0.100 ng/mL) in patients suffering from metastasizing PAC presented an unfavorable prognostic outcome. By correlating the ITGB6 tissue expression in primary and metastatic PAC with clinical parameters, we found that positive ITGB6 expression in the tumor tissue is linked to increased serum ITGB6 levels in nonmetastatic PAC and correlates with carbohydrate antigen 19-9 and clinical outcome. Our findings suggest that ITGB6 might serve as a novel serum biomarker for early diagnosis and prognosis of PAC. Given the limited specificity and sensitivity of currently used carbohydrate antigen 19-9-based assays, ITGB6 may have the potential to improve the diagnostic accuracy for PAC.
Identifiants
pubmed: 34388137
doi: 10.14309/ctg.0000000000000395
pii: 01720094-202108000-00009
pmc: PMC8367066
doi:
Substances chimiques
Antigens, Tumor-Associated, Carbohydrate
0
Biomarkers, Tumor
0
Integrin beta Chains
0
carbohydrate antigen 199, human
0
integrin beta6
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e00395Informations de copyright
Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.
Références
Li D, Xie K, Wolff R, et al. Pancreatic cancer. Lancet 2004;363:1049–57.
Cwik G, Wallner G, Skoczylas T, et al. Cancer antigens 19-9 and 125 in the differential diagnosis of pancreatic mass lesions. Arch Surg 2006;141:968–74.
Rahib L, Smith BD, Aizenberg R, et al. Projecting cancer incidence and deaths to 2030: The unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res 2014;74:2913–21.
Pleskow DK, Berger HJ, Gyves J, et al. Evaluation of a serologic marker, CA19-9, in the diagnosis of pancreatic cancer. Ann Intern Med 1989;110:704–9.
Cohen JD, Li L, Wang Y, et al. Detection and localization of surgically resectable cancers with a multi-analyte blood test. Science 2018;359:926–30.
Fahrmann JF, Bantis LE, Capello M, et al. A plasma-derived protein-metabolite multiplexed panel for early-stage pancreatic cancer. J Natl Cancer Inst 2019;111:372–9.
Li Z, Lin P, Gao C, et al. Integrin beta6 acts as an unfavorable prognostic indicator and promotes cellular malignant behaviors via ERK-ETS1 pathway in pancreatic ductal adenocarcinoma (PDAC). Tumor Biol 2016;37:5117–31.
Breuss JM, Gillett N, Lu L, et al. Restricted distribution of integrin beta 6 mRNA in primate epithelial tissues. J Histochem Cytochem 1993;41:1521–7.
Breuss JM, Gallo J, DeLisser HM, et al. Expression of the beta 6 integrin subunit in development, neoplasia and tissue repair suggests a role in epithelial remodeling. J Cell Sci 1995;108:2241–51.
Sipos B, Hahn D, Carceller A, et al. Immunohistochemical screening for beta6-integrin subunit expression in adenocarcinomas using a novel monoclonal antibody reveals strong up-regulation in pancreatic ductal adenocarcinomas in vivo and in vitro. Histopathology 2004;45:226–6.
Bengs S, Becker E, Busenhart P, et al. Beta6-integrin serves as a novel serum tumor marker for colorectal carcinoma. Int J Cancer 2019;145:678–5.
McShane LM, Altman DG, Sauerbrei W, et al. Reporting recommendations for tumor Marker prognostic studies (REMARK). Nat Clin Pract Urol 2005;2:416–2.
Akhoundova D, Hussung S, Fritsch RM. Precision oncology for hepato-pancreato-biliary (HPB) cancers: State of the art and future directions. Healthbook TIMES Onco Hema 2020;5:52–9.
Kleeff J, Korc M, Apte, et al. Pancreatic cancer. Nat Rev Dis Primers 2016;2:16022.
Paganuzzi M, Onetto M, Marroni P, et al. CA 19-9 and CA 50 in benign and malignant pancreatic and biliary diseases. Cancer 1988;61:2100–8.
Kim HJ, Kim MH, Myung SJ, et al. A new strategy for the application of CA19-9 in the differentiation of pancreaticobiliary cancer: Analysis using a receiver operating characteristic curve. Am J Gastroenterol 1999;94:1941–6.
Lamerz R. Role of tumour markers, cytogenetics. Ann Oncol 1999;10:145–9.
Tempero MA, Uchida E, Takasaki H, et al. Relationship of carbohydrate antigen 19-9 and Lewis antiges in panreatic cancer. Cancer Res 1987;47:5501–3.