Upregulation and epigenetic modification of the creatine transporter SLC6A8 in non-small cell lung cancer.

Autor:	Kuempers C; Institute of Pathology, University Hospital Schleswig-Holstein, Campus Luebeck, Luebeck, Germany. christiane.kuempers@uksh.de.; Airway Research Center North (ARCN), Member of the German Center for Lung Research (DZL), Großhansdorf, Germany., Schnepf K; Medical Clinic III, Pulmonology, University Hospital Schleswig-Holstein, Campus Luebeck, Luebeck, Germany., Marwitz S; Airway Research Center North (ARCN), Member of the German Center for Lung Research (DZL), Großhansdorf, Germany.; Histology, Research Center Borstel-Leibniz Lung Center, Borstel, Germany., Watermann C; Institute of Pathology, University Hospital Schleswig-Holstein, Campus Luebeck, Luebeck, Germany., Scheel AH; Institute of Pathology, University Hospital of Cologne, University of Cologne, Cologne, Germany., Fischer RN; Lung Cancer Group Cologne, Department I for Internal Medicine and Center for Integrated Oncology Aachen Bonn Cologne Dusseldorf, Faculty of Medicine and University Hospital of Cologne, University of Cologne, Cologne, Germany., Ammerpohl O; Airway Research Center North (ARCN), Member of the German Center for Lung Research (DZL), Großhansdorf, Germany.; Institute of Human Genetics, University Medical Center Ulm, Ulm, Germany., Perner S; Institute for Hematopathology Hamburg, Hamburg, Germany., Drömann D; Airway Research Center North (ARCN), Member of the German Center for Lung Research (DZL), Großhansdorf, Germany.; Medical Clinic III, Pulmonology, University Hospital Schleswig-Holstein, Campus Luebeck, Luebeck, Germany., Goldmann T; Airway Research Center North (ARCN), Member of the German Center for Lung Research (DZL), Großhansdorf, Germany.; Histology, Research Center Borstel-Leibniz Lung Center, Borstel, Germany.
Jazyk:	angličtina
Zdroj:	Histology and histopathology [Histol Histopathol] 2024 Jul; Vol. 39 (7), pp. 867-876. Date of Electronic Publication: 2024 Mar 07.
DOI:	10.14670/HH-18-731
Abstrakt:	Introduction: Lung cancer is a major cause of cancer-related death worldwide and effective therapies, besides surgery, are available only for a small proportion of patients. Since cellular respiration is known to be broadly altered in malignant tumors, the cellular processes of respiration can be a potential therapeutic target. One important element of cellular respiration is creatine and its transport by the creatine transporter SLC6A8. Here we describe the expression of SLC6A8 at the RNA and protein level, epigenetic modifications as well as survival analysis in NSCLC tissues and matched controls. Materials and Methods: We analyzed epigenetic modifications of the SLC68A gene in 32 patients, of which 18 were additionally analyzed by transcriptome analysis. The expression of SLC6A8 at the protein level was assessed by immunohistochemistry using an independent cohort and correlated with clinicopathological data including survival. Kaplan-Meier analysis was performed to analyze the possible effects of the transcriptional levels of SLC6A8 in another separate cohort (n=1925). Results: SLC6A8 loci are epigenetically modified in NSCLC compared with tumor-free controls. SLC6A8 is upregulated in NSCLC at the RNA and protein level. High mRNA expression of SLC6A8 was associated with an overall poor prognosis in lung adenocarcinoma patients and displayed the strongest adverse prognostic effect in male smokers with adenocarcinomas. Results of transcriptome analysis were partially confirmed at the protein level. Conclusions: Our results suggest an important role of creatine and its transport via SLC6A8 in NSCLC. (©The Author(s) 2024. Open Access. This article is licensed under a Creative Commons CC-BY International License.)
Databáze:	MEDLINE
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