Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Feb;25(1):228-239.
doi: 10.1007/s11307-022-01791-5. Epub 2022 Dec 27.

Data-Driven Identification of Targets for Fluorescence-Guided Surgery in Non-Small Cell Lung Cancer

Ruben P J Meijer #  1   2 , Lisanne K A Neijenhuis #  1   2 , Annette P Zeilstra  1 , Sophie F Roerink  3 , Shadhvi S Bhairosingh  1 , Denise E Hilling  1   4 , J Sven D Mieog  1 , Peter J K Kuppen  1 , Cornelis F M Sier  1   5 , Jerry Braun  6 , Jacobus Burggraaf  1   2 , Alexander L Vahrmeijer  1 , Danielle Cohen  7 , Merlijn Hutteman  8   9
Affiliations

Data-Driven Identification of Targets for Fluorescence-Guided Surgery in Non-Small Cell Lung Cancer

Ruben P J Meijer et al. Mol Imaging Biol. 2023 Feb.

Abstract

Purpose: Intraoperative identification of lung tumors can be challenging. Tumor-targeted fluorescence-guided surgery can provide surgeons with a tool for real-time intraoperative tumor detection. This study evaluated cell surface biomarkers, partially selected via data-driven selection software, as potential targets for fluorescence-guided surgery in non-small cell lung cancers: adenocarcinomas (ADC), adenocarcinomas in situ (AIS), and squamous cell carcinomas (SCC).

Procedures: Formalin-fixed paraffin-embedded tissue slides of resection specimens from 15 patients with ADC and 15 patients with SCC were used and compared to healthy tissue. Molecular targets were selected based on two strategies: (1) a data-driven selection using > 275 multi-omics databases, literature, and experimental evidence; and (2) the availability of a fluorescent targeting ligand in advanced stages of clinical development. The selected targets were carbonic anhydrase 9 (CAIX), collagen type XVII alpha 1 chain (collagen XVII), glucose transporter 1 (GLUT1), G protein-coupled receptor 87 (GPR87), transmembrane protease serine 4 (TMPRSS4), carcinoembryonic antigen (CEA), epithelial cell adhesion molecule (EpCAM), folate receptor alpha (FRα), integrin αvβ6 (αvβ6), and urokinase-type plasminogen activator receptor (uPAR). Tumor expression of these targets was assessed by immunohistochemical staining. A total immunostaining score (TIS, range 0-12), combining the percentage and intensity of stained cells, was calculated. The most promising targets in ADC were explored in six AIS tissue slides to explore its potential in non-palpable lesions.

Results: Statistically significant differences in TIS between healthy lung and tumor tissue for ADC samples were found for CEA, EpCAM, FRα, αvβ6, CAIX, collagen XVII, GLUT-1, and TMPRSS4, and of these, CEA, CAIX, and collagen XVII were also found in AIS. For SCC, EpCAM, uPAR, CAIX, collagen XVII, and GLUT-1 were found to be overexpressed.

Conclusions: EpCAM, CAIX, and Collagen XVII were identified using concomitant use of data-driven selection software and clinical evidence as promising targets for intraoperative fluorescence imaging for both major subtypes of non-small cell lung carcinomas.

Keywords: Data-driven selection; Immunohistochemical staining; Lung cancer; Molecular imaging; Near-infrared fluorescence imaging; Target selection.

PubMed Disclaimer

References

    1. Global Burden of Disease Cancer Collaboration, Fitzmaurice C, Abate D, Abbasi N, Abbastabar H, Abd-Allah F, Abdel-Rahman O, Abdelalim A, Abdoli A, Abdollahpour I et al (2019) Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 29 cancer groups, 1990 to 2017: a systematic analysis for the global burden of disease study. JAMA Oncol 5(12):1749–1768
    1. National Lung Screening Trial Research T, Aberle DR, Adams AM, Berg CD, Black WC, Clapp JD, Fagerstrom RM, Gareen IF, Gatsonis C, Marcus PM et al (2011) Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med 365(5):395–409 - DOI
    1. Walter JE, Heuvelmans MA, de Jong PA, Vliegenthart R, van Ooijen PMA, Peters RB, Ten Haaf K, Yousaf-Khan U, van der Aalst CM, de Bock GH et al (2016) Occurrence and lung cancer probability of new solid nodules at incidence screening with low-dose CT: analysis of data from the randomised, controlled NELSON trial. Lancet Oncol 17(7):907–916 - DOI - PubMed
    1. de Koning HJ, van der Aalst CM, de Jong PA, Scholten ET, Nackaerts K, Heuvelmans MA, Lammers JJ, Weenink C, Yousaf-Khan U, Horeweg N et al (2020) Reduced lung-cancer mortality with volume CT screening in a randomized trial. N Engl J Med 382(6):503–513 - DOI - PubMed
    1. Yamato Y, Tsuchida M, Watanabe T, Aoki T, Koizumi N, Umezu H, Hayashi J (2001) Early results of a prospective study of limited resection for bronchioloalveolar adenocarcinoma of the lung. Ann Thorac Surg 71(3):971–974 - DOI - PubMed

Substances

LinkOut - more resources