Cararo-Lopes Eduardo, Sawant Akshada, Moore Dirk, Ke Hua, Shi Fuqian, Laddha Saurabh, Chen Ying, Sharma Anchal, Naumann Jake, Guo Jessie Yanxiang, Gomez Maria, Ibrahim Maria, Smith Tracey L, Riedlinger Gregory M, Lattime Edmund C, Trooskin Stanley, Ganesan Shridar, Su Xiaoyang, Pasqualini Renata, Arap Wadih, De Subhajyoti, Chan Chang S, White Eileen
Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903; USA.
Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, NJ 08903, USA.
medRxiv. 2023 Mar 10:2023.03.09.23287037. doi: 10.1101/2023.03.09.23287037.
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.
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.
分化型甲状腺癌（DTC）每年在全球影响着成千上万人的生命。通常，DTC是一种可治疗且预后良好的疾病。然而，一些患者会接受部分或全甲状腺切除术及放射性碘治疗，以预防局部疾病复发和转移。不幸的是，甲状腺切除术和/或放射性碘治疗常常会使生活质量恶化，在惰性DTC病例中可能并无必要。这种临床情况凸显了对DTC进行精确分子诊断的未满足需求，而这应该决定适当的治疗方法。在此，我们提出一种差异多组学模型方法，以区分正常甲状腺组织与甲状腺肿瘤，并指示甲状腺乳头状癌（PTC，DTC的一个子类）中潜在的转移性疾病。基于PTC患者样本，我们的数据表明，核DNA和线粒体DNA突变负担增加、肿瘤内异质性、端粒长度缩短以及代谢谱改变反映了转移性疾病的可能性。具体而言，这些患者的正常和肿瘤甲状腺组织具有独特但明确的代谢谱，其中合成代谢产物和/或其他与肿瘤细胞能量维持相关的代谢产物水平较高。总之，这项工作表明，差异和综合的多组学方法可能会改善DTC的管理，或许可避免不必要的甲状腺切除和/或放射性碘治疗。精心设计的前瞻性转化临床试验最终将证明这种靶向分子方法的价值。
在本文中，我们提出了一种新的综合代谢、基因组和细胞病理学方法，用于在传统方法失效时诊断分化型甲状腺癌。此外，我们提出了代谢和基因组标志物，以帮助预测高危甲状腺乳头状癌。这两者可能都是重要工具，可避免不必要的手术和/或放射性碘治疗，这些治疗对患者生活质量的恶化可能超过患有惰性甲状腺结节的情况。
