Identification and Validation of Esophageal Squamous Cell Carcinoma Targets for Fluorescence Molecular Endoscopy

Autor: Rudolf S N Fehrmann, Matthijs D. Linssen, Steven J de Jongh, Marcel A. T. M. van Vugt, W. T. R. Hooghiemstra, Qingfeng Huang, Marjory Koller, Wouter B. Nagengast, Xiaojuan Zhao, Enmin Li
Přispěvatelé: Guided Treatment in Optimal Selected Cancer Patients (GUTS), Damage and Repair in Cancer Development and Cancer Treatment (DARE)
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Pathology
Microarray
Colorectal cancer
PROTEIN
BIGLYCAN EXPRESSION
COLORECTAL-CANCER
GLUTATHIONE-S-TRANSFERASE
Medicine
fluorescence molecular endoscopy
Biology (General)
early detection
Spectroscopy
Oligonucleotide Array Sequence Analysis
Glucose Transporter Type 1
medicine.diagnostic_test
COLON-CANCER
PROLIFERATION
General Medicine
bioinformatics
Immunohistochemistry
Fluorescence
Neoplasm Proteins
Computer Science Applications
Gene Expression Regulation
Neoplastic
Chemistry
Esophageal Squamous Cell Carcinoma
medicine.medical_specialty
QH301-705.5
squamous high-grade dysplasia
Sensitivity and Specificity
Article
Catalysis
Inorganic Chemistry
Esophagus
POOR-PROGNOSIS
CLINICOPATHOLOGICAL FEATURES
Humans
RNA
Messenger
Physical and Theoretical Chemistry
QD1-999
Molecular Biology
business.industry
Gene Expression Profiling
Organic Chemistry
LYMPH-NODE METASTASIS
Endoscopy
medicine.disease
mRNA profiling
digestive system diseases
Early Diagnosis
Dysplasia
Molecular imaging
business
Ex vivo
TISSUE-SPECIFIC EXPRESSION
Zdroj: International Journal of Molecular Sciences, Vol 22, Iss 9270, p 9270 (2021)
International Journal of Molecular Sciences, 22(17):9270, 1-16. MDPI AG
International Journal of Molecular Sciences
Volume 22
Issue 17
ISSN: 1422-0067
Popis: Dysplasia and intramucosal esophageal squamous cell carcinoma (ESCC) frequently go unnoticed with white-light endoscopy and, therefore, progress to invasive tumors. If suitable targets are available, fluorescence molecular endoscopy might be promising to improve early detection. Microarray expression data of patient-derived normal esophagus (n = 120) and ESCC samples (n = 118) were analyzed by functional genomic mRNA (FGmRNA) profiling to predict target upregulation on protein levels. The predicted top 60 upregulated genes were prioritized based on literature and immunohistochemistry (IHC) validation to select the most promising targets for fluorescent imaging. By IHC, GLUT1 showed significantly higher expression in ESCC tissue (30 patients) compared to the normal esophagus adjacent to the tumor (27 patients) (p <
0.001). Ex vivo imaging of GLUT1 with the 2-DG 800CW tracer showed that the mean fluorescence intensity in ESCC (n = 17) and high-grade dysplasia (HGD, n = 13) is higher (p <
0.05) compared to that in low-grade dysplasia (LGD) (n = 7) and to the normal esophagus adjacent to the tumor (n = 5). The sensitivity and specificity of 2-DG 800CW to detect HGD and ESCC is 80% and 83%, respectively (ROC = 0.85). We identified and validated GLUT1 as a promising molecular imaging target and demonstrated that fluorescent imaging after topical application of 2-DG 800CW can differentiate HGD and ESCC from LGD and normal esophagus.
Databáze: OpenAIRE
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