Analysis of the Single-Cell Heterogeneity of Adenocarcinoma Cell Lines and the Investigation of Intratumor Heterogeneity Reveals the Expression of Transmembrane Protein 45A (TMEM45A) in Lung Adenocarcinoma Cancer Patients

Neuperger, Patricia and Balog, József Ágoston and Tiszlavicz, László and Furák, József and Gémes, Nikolett and Kotogány, Edit and Szalontai, Klára Margit and Puskás, László and Szebeni, Gábor (2022) Analysis of the Single-Cell Heterogeneity of Adenocarcinoma Cell Lines and the Investigation of Intratumor Heterogeneity Reveals the Expression of Transmembrane Protein 45A (TMEM45A) in Lung Adenocarcinoma Cancer Patients. CANCERS, 14 (1). ISSN 2072-6694

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Abstract

Non-small cell lung cancer (NSCLC) is one of the main causes of cancer-related deaths worldwide. Intratumoral heterogeneity (ITH) is responsible for the majority of difficulties encountered in the treatment of lung-cancer patients. Therefore, the heterogeneity of NSCLC cell lines and primary lung adenocarcinoma was investigated by single-cell mass cytometry (CyTOF). Human NSCLC adenocarcinoma cells A549, H1975, and H1650 were studied at single-cell resolution for the expression pattern of 13 markers: GLUT1, MCT4, CA9, TMEM45A, CD66, CD274, CD24, CD326, pan-keratin, TRA-1-60, galectin-3, galectin-1, and EGFR. The intra- and inter-cell-line heterogeneity of A549, H1975, and H1650 cells were demonstrated through hypoxic modeling. Additionally, human primary lung adenocarcinoma, and non-involved healthy lung tissue were homogenized to prepare a single-cell suspension for CyTOF analysis. The single-cell heterogeneity was confirmed using unsupervised viSNE and FlowSOM analysis. Our results also show, for the first time, that TMEM45A is expressed in lung adenocarcinoma.

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