Background

Tumor mutation burden (TMB) as a prognostic marker for immunotherapy has shown prognostic value in many cancers. However, there is no systematic investigation on TMB in papillary thyroid carcinoma (PTC).

Methods

Based on the somatic mutation data of 487 PTC patients from The Cancer Genome Atlas (TCGA), TMB was calculated, and we classified the samples into high-TMB (H-TMB) and low-TMB (L-TMB) groups. Bioinformatics methods were used to explore the characteristics and potential mechanism of TMB in PTC.

Results

High TMB predicts shorter progression-free survival (PFS) (P < 0.001). TMB was positively correlated with age, stage, tumor size, metastasis, the male sex and tall cell PTC. Compared to the L-TMB group, the H-TMB group presented with lower immune cell infiltration, a higher proportion of tumor-promoting immune cells (M0 macrophages, activated dendritic cells and monocytes) and a lower proportion of antitumor immune cells (M1 macrophages, CD8⁺ T cells and B cells). Additionally, the characteristics displayed by different TMB groups were not driven by critical driver mutations such as BRAF and RAS.

Conclusions

PTC patients with high TMB have a worse prognosis. By stratifying PTC patients according to their TMB, advanced PTC patients who are candidates for immunotherapy could be selected.

中文翻译：

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肿瘤突变负担高的甲状腺乳头状癌预后较差

背景

肿瘤突变负担（TMB）作为免疫治疗的预后标志物已显示出对许多癌症的预后价值。但是，目前尚无关于甲状腺乳头状癌（PTC）中TMB的系统研究。

方法

根据来自癌症基因组图谱（TCGA）的487 PTC患者的体细胞突变数据，计算了TMB，并将样本分为高TMB（H-TMB）和低TMB（L-TMB）组。利用生物信息学方法探讨了TMB在PTC中的特征和潜在机制。

结果

高TMB预测较短的无进展生存期（PFS）（P  <0.001）。TMB与年龄，分期，肿瘤大小，转移，男性和高细胞PTC呈正相关。与L-TMB组相比，H-TMB组的免疫细胞浸润率较低，促肿瘤的免疫细胞（M0巨噬细胞，活化的树突状细胞和单核细胞）的比例较高，而抗肿瘤免疫细胞（M1巨噬细胞）的比例较低，CD8 ⁺ T细胞和B细胞）。此外，由不同的TMB组显示的特性不是由诸如BRAF和RAS的关键驱动程序突变驱动的。

结论

高TMB的PTC患者预后较差。通过根据他们的TMB对PTC患者进行分层，可以选择可以进行免疫治疗的晚期PTC患者。