甲状腺乳头状癌突变等位基因肿瘤异质性的临床及其与预后相关性研究

Clinical and prognostic significance of mutant-allele tumor heterogeneity in thyroid papillary carcinoma

目的探讨突变等位基因肿瘤异质性(MATH)在甲状腺乳头状癌(PTC)中的临床意义。方法从癌症基因图谱公共数据集下载并预处理PTC肿瘤测序数据及临床资料数据,分析MATH与PTC临床病理特征的相关性,使用Kaplan-Meier法进行生存分析,验证MATH对PTC患者的预后价值。结果 PTC患者中MATH值为2.57-93.72,平均29.45±16.19;将≥29.45者纳入高MATH组,<29.45者纳入低MATH组。高MATH组与低MATH组的患者年龄、性别、临床分期、BRAF基因型差异无统计学意义(P> 0.05)。MATH不是PTC患者总体生存期(OS)的显著预测因素(P=0.4595);在BRAF突变型PTC患者中,高MATH者的OS低于低MATH者(P=0.0252),而在BRAF野生型PTC患者中,高MATH者的OS高于低MATH者(P=0.0495)。结论 MATH可在BRAF突变型和野生型亚组中可预测PTC患者的预后及指导临床治疗。

Objective To investigate the clinical significance of mutant-allele tumor heterogeneity(MATH) levels in papillary thyroid carcinoma(PTC). Methods The sequencing data and clinical data of PTC were downloaded from the public data sets of The Cancer Genome Atlas(TCGA) and preprocessed. The correlation between MATH and clinicopathological features of PTC was analyzed. Kaplan-Meier survival analysis was used to verify the prognostic value of MATH in patients with PTC. Results MATH scores ranged from 2.57 to 93.72 in PTC patients, with an average of 29.45±16.19. The patients with an MATH score ≥ 29.45 were assigned to a high-MATH group, and those with an MATH score < 29.45 were assigned to a low-MATH group. There was no significant difference in age, gender, tumor stage and BRAF genotype between the high-MATH group and low-MATH group(P > 0.05). MATH was not a significant predictor of overall survival(OS) in patients with PTC(P=0.4595). Whereas in PTC patients with BRAF mutation, the OS in patients with a high MATH score was significantly worse than that in patients with a low MATH score(P=0.0252). In PTC patients with wild-type BRAF, the OS was significantly better in patients with a high MATH score than in those with a low MATH(P=0.0495). Conclusion MATH can predict the prognosis of PTC patients with wild type or mutant BRAF, which can be used to guide clinical treatment.