Integrated metabolic and genetic analysis reveals distinct features of primary differentiated thyroid cancer and its metastatic potential in humans.

Autor:	Cararo-Lopes E; Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903; USA.; Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, NJ 08903, USA., Sawant A; Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903; USA., Moore D; Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903; USA.; Department of Biostatistics and Epidemiology, Rutgers School of Public Health, Piscataway, NJ 08854, USA., Ke H; Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903; USA., Shi F; Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903; USA., Laddha S; Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903; USA., Chen Y; Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903; USA., Sharma A; Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903; USA., Naumann J; Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903; USA., Guo JY; Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903; USA.; Department of Medicine, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ 08903, USA.; Department of Chemical Biology, Rutgers Ernest Mario School of Pharmacy, Piscataway, NJ 08854, USA., Gomez M; Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903; USA., Ibrahim M; Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903; USA., Smith TL; Rutgers Cancer Institute of New Jersey, Newark, NJ 07101, USA.; Division of Cancer Biology, Department of Radiation Oncology, Rutgers New Jersey Medical School, Newark, NJ 07103, USA., Riedlinger GM; Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903; USA., Lattime EC; Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903; USA.; Department of Surgery, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ 08903, USA., Trooskin S; Department of Surgery, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ 08903, USA., Ganesan S; Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903; USA.; Department of Medicine, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ 08903, USA., Su X; Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903; USA.; Department of Medicine, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ 08903, USA., Pasqualini R; Rutgers Cancer Institute of New Jersey, Newark, NJ 07101, USA.; Division of Cancer Biology, Department of Radiation Oncology, Rutgers New Jersey Medical School, Newark, NJ 07103, USA., Arap W; Rutgers Cancer Institute of New Jersey, Newark, NJ 07101, USA.; Division of Hematology/Oncology, Department of Medicine, Rutgers New Jersey Medical School, Newark, NJ 07103, USA., De S; Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903; USA., Chan CS; Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903; USA.; Department of Medicine, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ 08903, USA., White E; Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903; USA.; Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, NJ 08903, USA.; Ludwig Princeton Branch, Ludwig Institute for Cancer Research, Princeton University, Princeton, NJ 08544.
Jazyk:	angličtina
Zdroj:	MedRxiv : the preprint server for health sciences [medRxiv] 2023 Mar 10. Date of Electronic Publication: 2023 Mar 10.
DOI:	10.1101/2023.03.09.23287037
Abstrakt:	Differentiated thyroid cancer (DTC) affects thousands of lives worldwide every year. Typically, DTC is a treatable disease with a good prognosis. Yet, some patients are subjected to partial or total thyroidectomy and radioiodine therapy to prevent local disease recurrence and metastasis. Unfortunately, thyroidectomy and/or radioiodine therapy often worsen(s) the quality of life and might be unnecessary in indolent DTC cases. This clinical setting highlights the unmet need for a precise molecular diagnosis of DTC, which should dictate appropriate therapy. Here we propose a differential multi-omics model approach to distinguish normal gland from thyroid tumor and to indicate potential metastatic diseases in papillary thyroid cancer (PTC), a sub-class of DTC. Based on PTC patient samples, our data suggest that elevated nuclear and mitochondrial DNA mutational burden, intratumor heterogeneity, shortened telomere length, and altered metabolic profile reflect the potential for metastatic disease. Specifically, normal and tumor thyroid tissues from these patients had a distinct yet well-defined metabolic profile with high levels of anabolic metabolites and/or other metabolites associated with the energy maintenance of tumor cells. Altogether, this work indicates that a differential and integrated multi-omics approach might improve DTC management, perhaps preventing unnecessary thyroid gland removal and/or radioiodine therapy. Well-designed, prospective translational clinical trials will ultimately show the value of this targeted molecular approach. Translational Relevance: In this article, we propose a new integrated metabolic, genomic, and cytopathologic methods to diagnose Differentiated Thyroid Cancer when the conventional methods failed. Moreover, we suggest metabolic and genomic markers to help predict high-risk Papillary Thyroid Cancer. Both might be important tools to avoid unnecessary surgery and/or radioiodine therapy that can worsen the quality of life of the patients more than living with an indolent Thyroid nodule.
Databáze:	MEDLINE
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