Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
BMC Cancer
Published in: BMC Cancer 1/2023

Open Access 01-12-2023 | Glioma | Research

Tracking tumor alteration in glioma through serum fibroblast activation protein combined with image

Authors: Xiao-song Yang, Peng zhu, Rong-Xing Xie, Peng-fei Chen, Hong Liu, Xiao-Man Cheng, Zheng-Quan Zhu, Xiao-min Peng, Hai-bin Liu, Qun-Ying Yang, Jun-Qi Li, Ji Zhang

Published in: BMC Cancer | Issue 1/2023

Login to get access

Abstract

Purpose

Detecting tumor progression of glioma continues to pose a formidable challenge. The role of fibroblast activation protein (FAP) in gliomas has been demonstrated to facilitate tumor progression. Glioma-circulating biomarkers have not yet been used in clinical practice. This study seeks to evaluate the feasibility of glioma detection through the utilization of a serum FAP marker.

Methods

We adopted enzyme-linked immunosorbent assay (ELISA) technique to quantify the relative FAP level of serum autoantibodies in a cohort of 87 gliomas. The correlation between preoperative serum autoantibody relative FAP levels and postoperative pathology, including molecular pathology was investigated. A series of FAP tests were conducted on 33 cases of malignant gliomas in order to ascertain their efficacy in monitoring the progression of the disease in relation to imaging observations. To validate the presence of FAP expression in tumors, immunohistochemistry was conducted on four gliomas employing a FAP-specific antibody. Additionally, the investigation encompassed the correlation between postoperative tumor burden, as assessed through volumetric analysis, and the relative FAP level of serum autoantibodies.

Results

A considerable proportion of gliomas exhibited a significantly increased level of serum autoantibody relative FAP level. This elevation was closely associated with both histopathology and molecular pathology, and demonstrated longitudinal fluctuations and variations corresponding to the progression of the disease The correlation between the rise in serum autoantibody relative FAP level and tumor progression and/or exacerbation of symptoms was observed.

Conclusions

The measurement of serum autoantibody relative FAP level can be used to detect the disease as a valuable biomarker. The combined utilization of its detection alongside MR imaging has the potential to facilitate a more accurate and prompt diagnosis.
Literature
1.
Ostrom QT, Cioffi G, Gittleman H, Patil N, Waite K, Kruchko C, Barnholtz-Sloan JS. CBTRUS Statistical Report: primary brain and other Central Nervous System tumors diagnosed in the United States in 2012–2016. Neuro Oncol. 2019;21(Suppl 5):v1–v100.CrossRefPubMedPubMedCentral
2.
Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer statistics 2020: GLOBOCAN estimates of incidence and Mortality Worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209–49.CrossRefPubMed
3.
Tan AC, Ashley DM, Lopez GY, Malinzak M, Friedman HS, Khasraw M. Management of glioblastoma: state of the art and future directions. CA Cancer J Clin. 2020;70(4):299–312.CrossRefPubMed
4.
Karsy M, Neil JA, Guan J, Mahan MA, Colman H, Jensen RL. A practical review of prognostic correlations of molecular biomarkers in glioblastoma. Neurosurg Focus. 2015;38(3):E4.CrossRefPubMed
5.
Weller M, van den Bent M, Preusser M, Le Rhun E, Tonn JC, Minniti G, Bendszus M, Balana C, Chinot O, Dirven L, et al. EANO guidelines on the diagnosis and treatment of diffuse gliomas of adulthood. Nat Rev Clin Oncol. 2021;18(3):170–86.CrossRefPubMed
6.
Weller M, van den Bent M, Tonn JC, Stupp R, Preusser M, Cohen-Jonathan-Moyal E, Henriksson R, Le Rhun E, Balana C, Chinot O, et al. European Association for Neuro-Oncology (EANO) guideline on the diagnosis and treatment of adult astrocytic and oligodendroglial gliomas. Lancet Oncol. 2017;18(6):e315–29.CrossRefPubMed
7.
Rettig WJ, Chesa PG, Beresford HR, Feickert HJ, Jennings MT, Cohen J, Oettgen HF, Old LJ. Differential expression of cell surface antigens and glial fibrillary acidic protein in human astrocytoma subsets. Cancer Res. 1986;46(12 Pt 1):6406–12.PubMed
8.
Park JE, Lenter MC, Zimmermann RN, Garin-Chesa P, Old LJ, Rettig WJ. Fibroblast activation protein, a dual specificity serine protease expressed in reactive human Tumor stromal fibroblasts. J Biol Chem. 1999;274(51):36505–12.CrossRefPubMed
9.
Busek P, Balaziova E, Matrasova I, Hilser M, Tomas R, Syrucek M, Zemanova Z, Krepela E, Belacek J, Sedo A. Fibroblast activation protein alpha is expressed by transformed and stromal cells and is associated with mesenchymal features in glioblastoma. Tumour Biol. 2016;37(10):13961–71.CrossRefPubMed
10.
Mentlein R, Hattermann K, Hemion C, Jungbluth AA, Held-Feindt J. Expression and role of the cell surface protease seprase/fibroblast activation protein-α (FAP-α) in astroglial tumors. Biol Chem. 2011;392(3):199–207.CrossRefPubMed
11.
Liu F, Qi L, Liu B, Liu J, Zhang H, Che D, Cao J, Shen J, Geng J, Bi Y, et al. Fibroblast activation protein overexpression and clinical implications in solid tumors: a meta-analysis. PLoS ONE. 2015;10(3):e0116683.CrossRefPubMedPubMedCentral
12.
Röhrich M, Loktev A, Wefers AK, Altmann A, Paech D, Adeberg S, Windisch P, Hielscher T, Flechsig P, Floca R, et al. IDH-wildtype glioblastomas and grade III/IV IDH-mutant gliomas show elevated tracer uptake in fibroblast activation protein-specific PET/CT. Eur J Nucl Med Mol Imaging. 2019;46(12):2569–80.CrossRefPubMed
13.
Li M, Li G, Kiyokawa J, Tirmizi Z, Richardson LG, Ning J, Das S, Martuza RL, Stemmer-Rachamimov A, Rabkin SD, et al. Characterization and oncolytic virus targeting of FAP-expressing tumor-associated pericytes in glioblastoma. Acta Neuropathol Commun. 2020;8(1):221.CrossRefPubMedPubMedCentral
14.
Pandya DN, Sinha A, Yuan H, Mutkus L, Stumpf K, Marini FC, Wadas TJ. Imaging of fibroblast activation protein alpha expression in a Preclinical Mouse Model of Glioma using Positron Emission Tomography. Molecules 2020, 25(16).
15.
Shi Y, Kong Z, Liu P, Hou G, Wu J, Ma W, Cheng X, Wang Y. Oncogenesis, Microenvironment Modulation and clinical potentiality of FAP in Glioblastoma: lessons learned from other solid tumors. Cells 2021, 10(5).
16.
17.
Persano L, Rampazzo E, Basso G, Viola G. Glioblastoma cancer stem cells: role of the microenvironment and therapeutic targeting. Biochem Pharmacol. 2013;85(5):612–22.CrossRefPubMed
18.
19.
20.
Liao Y, Ni Y, He R, Liu W, Du J. Clinical implications of fibroblast activation protein-α in non-small cell Lung cancer after curative resection: a new predictor for prognosis. J Cancer Res Clin Oncol. 2013;139(9):1523–8.CrossRefPubMed
21.
Moreno-Ruiz P, Corvigno S, Te Grootenhuis NC, La Fleur L, Backman M, Strell C, Mezheyeuski A, Hoelzlwimmer G, Klein C, Botling J, et al. Stromal FAP is an Independent poor prognosis marker in non-small cell lung adenocarcinoma and associated with p53 mutation. Lung Cancer. 2021;155:10–9.CrossRefPubMed
22.
Li M, Cheng X, Rong R, Gao Y, Tang X, Chen Y. High expression of fibroblast activation protein (FAP) predicts poor outcome in high-grade serous Ovarian cancer. BMC Cancer. 2020;20(1):1032.CrossRefPubMedPubMedCentral
23.
Calvete J, Larrinaga G, Errarte P, Martin AM, Dotor A, Esquinas C, Nunes-Xavier CE, Pulido R, Lopez JI, Angulo JC. The coexpression of fibroblast activation protein (FAP) and basal-type markers (CK 5/6 and CD44) predicts prognosis in high-grade invasive urothelial carcinoma of the bladder. Hum Pathol. 2019;91:61–8.CrossRefPubMed
24.
Balaziova E, Vymola P, Hrabal P, Mateu R, Zubal M, Tomas R, Netuka D, Kramar F, Zemanova Z, Svobodova K et al. Fibroblast Activation Protein Expressing Mesenchymal Cells Promote Glioblastoma Angiogenesis. Cancers (Basel) 2021, 13(13).
25.
Hamson EJ, Keane FM, Tholen S, Schilling O, Gorrell MD. Understanding fibroblast activation protein (FAP): substrates, activities, expression and targeting for cancer therapy. Proteom Clin Appl. 2014;8(5–6):454–63.CrossRef
26.
Clavreul A, Etcheverry A, Chassevent A, Quillien V, Avril T, Jourdan ML, Michalak S, Francois P, Carre JL, Mosser J, et al. Isolation of a new cell population in the glioblastoma microenvironment. J Neurooncol. 2012;106(3):493–504.CrossRefPubMed
27.
Abbas O, Richards JE, Mahalingam M. Fibroblast-activation protein: a single marker that confidently differentiates morpheaform/infiltrative basal cell carcinoma from desmoplastic trichoepithelioma. Mod Pathol. 2010;23(11):1535–43.CrossRefPubMed
28.
Liu R, Li H, Liu L, Yu J, Ren X. Fibroblast activation protein: a potential therapeutic target in cancer. Cancer Biol Ther. 2012;13(3):123–9.CrossRefPubMed
29.
Solano-Iturri JD, Beitia M, Errarte P, Calvete-Candenas J, Etxezarraga MC, Loizate A, Echevarria E, Badiola I, Larrinaga G. Altered expression of fibroblast activation protein-α (FAP) in colorectal adenoma-carcinoma sequence and in lymph node and liver metastases. Aging. 2020;12(11):10337–58.CrossRefPubMedPubMedCentral
30.
Miao Y, Deng Y, Liu J, Wang J, Hu B, Hao S, Wang H, Zhang Z, Jin Z, Zhang Y, et al. Anti-cancer effect of targeting fibroblast activation protein alpha in glioblastoma through remodeling macrophage phenotype and suppressing Tumor progression. CNS Neurosci Ther. 2023;29(3):878–92.CrossRefPubMed
31.
Solano-Iturri JD, Errarte P, Etxezarraga MC, Echevarria E, Angulo J, López JI, Larrinaga G. Altered tissue and plasma levels of fibroblast activation Protein-α (FAP) in renal tumours. Cancers 2020, 12(11).
32.
Lee KN, Jackson KW, Christiansen VJ, Lee CS, Chun J-G, McKee PA. Antiplasmin-cleaving enzyme is a soluble form of fibroblast activation protein. Blood. 2006;107(4):1397–404.CrossRefPubMed
33.
Liao Y, Xing S, Xu B, Liu W, Zhang G. Evaluation of the circulating level of fibroblast activation protein α for diagnosis of esophageal squamous cell carcinoma. Oncotarget. 2017;8(18):30050–62.CrossRefPubMedPubMedCentral
Metadata
Title
Tracking tumor alteration in glioma through serum fibroblast activation protein combined with image
Authors
Xiao-song Yang
Peng zhu
Rong-Xing Xie
Peng-fei Chen
Hong Liu
Xiao-Man Cheng
Zheng-Quan Zhu
Xiao-min Peng
Hai-bin Liu
Qun-Ying Yang
Jun-Qi Li
Ji Zhang
Publication date
01-12-2023
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2023
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-023-11544-4

Other articles of this Issue 1/2023

BMC Cancer 1/2023 Go to the issue

Research

Combining perineural invasion with staging improve the prognostic accuracy in colorectal cancer: a retrospective cohort study

Research

Early prediction of response to palliative chemotherapy in patients with stage-IV gastric and esophageal cancer

Study Protocol

Effects of sleep disturbances and circadian rhythms modifications on cognition in breast cancer women before and after adjuvant chemotherapy: the ICANSLEEP-1 protocol

Research

Automated Breast Ultrasound (ABUS)-based radiomics nomogram: an individualized tool for predicting axillary lymph node tumor burden in patients with early breast cancer

Research

99mTc-MAA accumulation within tumor in preoperative lung perfusion SPECT/CT associated with occult lymph node metastasis in patients with clinically N0 non-small cell lung cancer

Research

The effect of sarcopenia and sarcopenic obesity on survival in gastric cancer
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits