TP53和PI-3激酶/AKT途径中的致癌突变是晚期甲状腺癌生存的独立预测指标：分子筛选和治疗剂（大多数）程序的分析（大多数）程序
Oncogenic mutations in the TP53 and PI-3 kinase/AKT pathway are independent predictors of survival for advanced thyroid cancer: Analysis from the Molecular Screening and Therapeutics (MoST) program
影响因子:2.70000
分区:医学2区 / 外科2区
发表日期:2025 Jan
作者:
Elan Novis, Anthony Glover, John P Grady, Audrey Silvestri, Subotheni Thavaneswaran, Frank Lin, Mandy L Ballinger, David M Thomas
摘要
甲状腺癌在磷脂酰肌醇-3激酶/AKT途径中具有突变的预后较差。但是，关于组织学，突变概况和结果之间关系的知识仍在发展。这项研究评估了在常规治疗方面经历过进展的晚期甲状腺癌患者的基因组谱的预后价值。分析了为局部晚期，复发性或转移性癌症治疗治疗 - 难治性治疗治疗的患者招募的患者。患者的档案肿瘤样品进行了全面的基因组分析。特定的致癌突变和与癌症相关途径的存在与整体生存相关。从2018年到2021年，招募了4,955例患者，有44例（0.9％）诊断为甲状腺癌的44例甲状腺癌和剩余的卵泡衍生：17个差异化，13个差异化，13个差异化，分化良好，10种那天的throsplastic thros throid cancers cancers cycycers android cancers。在40个卵泡衍生的甲状腺癌样本中，有17个（42.5％）带有TP53突变，其次是11个BRAF V600E（27.5％），9，NRAS（22.5％），9，磷酸二醇糖酸醇-3激酶/AKT pathway（22.5％）（22.5％）和7％的促进剂促进剂，磷酸脂蛋白辛醇-3激酶/AKT pathway（22.5％）和7％的启动器（tre）。 TP53和磷脂酰肌醇-3激酶/AKT途径改变都与总生存率降低有关（危险比，5.19； 95％置信区间，1.59-16.70，p = .02，危险比，10.12; 10.12; 95％置信区间； 95％置信区间，1.611-63.76，p = .01）。 Cox回归显示组织学型甲状腺癌（危险比，12.93，p = .004），甲状腺癌分化差（危险比，5.19，p = .039）和TP53和/或/或磷脂酰肌醇-3激酶/Akt Pathway Pathway pathway pathway突变（4.73），4.73，p = = .039），p = 4.73，p =。 TP53和/或磷脂酰肌醇-3激酶/AKT途径突变与总体生存相关，与晚期甲状腺癌患者的组织类型相关。全面的基因组分析有可能为预后提供信息，并确定了晚期甲状腺癌患者的治疗靶标。
Abstract
Thyroid cancers with mutations in the phosphatidylinositol-3 kinase/AKT pathway have a poorer prognosis. However, knowledge about the relationship between histology, mutation profile, and outcomes is still developing. This study assessed the prognostic value of genomic profiles for patients with advanced thyroid cancer who experienced progression on conventional treatment.Patients recruited to a national clinical oncology program for treatment-refractory locally advanced, recurrent or metastatic cancers were analyzed. Patients' archival tumor samples underwent comprehensive genomic profiling. Specific oncogenic mutations and the presence of cancer related pathways were correlated with overall survival.From 2018 to 2021, 4,955 patients were recruited, with 44 (0.9%) having a diagnosis of thyroid cancer with 4 medullary and the remaining follicular derived: 17 differentiated, 13 poorly differentiated, and 10 anaplastic thyroid cancers. Of the 40 follicular-derived thyroid cancer samples, 17 (42.5%) carried TP53 mutations, followed by 11 with BRAF V600E (27.5%), 9 with NRAS (22.5%), 9 with mutations in the phosphatidylinositol-3 kinase/AKT pathway (22.5%), and 7 with TERT promoter mutations (17.5%). Both TP53 and phosphatidylinositol-3 kinase/AKT pathway alterations were associated with reduced overall survival (hazard ratio, 5.19; 95% confidence interval, 1.59-16.70, P = .02 and hazard ratio, 10.12; 95% confidence interval, 1.61-63.76, P = .01). Cox regression showed histologic type anaplastic thyroid cancer (hazard ratio, 12.93, P = .004), poorly differentiated thyroid cancer (hazard ratio, 5.19, P = .039), and TP53 and/or phosphatidylinositol-3 kinase/AKT pathway mutations (hazard ratio, 4.73, P = .017) were independently associated with overall survival.TP53 and/or phosphatidylinositol-3 kinase/AKT pathway mutations correlated with overall survival independently of histotype in patients with advanced thyroid cancer. Comprehensive genomic profiling has potential to inform prognosis, as well as identifying treatment targets for patients with advanced thyroid cancer.