Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Department of Head and Neck Surgery, Shanghai Cancer Center, Fudan University, Shanghai, China.
Endocrine. 2022 Dec;78(3):517-530. doi: 10.1007/s12020-022-03179-5. Epub 2022 Sep 7.
Patients with anaplastic thyroid cancer (ATC) have a very poor prognosis. Immunotherapy is a potential treatment, while the current outcome is limited which may be due to the complicated tumor microenvironment (TME). Tumor associated macrophages (TAMs) is the most abundant cell in the TME of ATC. We aimed to clarify the novel indicators based on TAM in ATC.
Transcriptome files were downloaded from the Gene Expression Omnibus (GEO) dataset. Weighted gene co-expression network analysis, cox regression, support vector machine, and random forest were utilized to identify TAM-related prognostic genes. Consensus clustering and principal component analysis were performed for integrated analysis. Moreover, external validation (Fudan University Shanghai Cancer Center cohort) was conducted in 23 ATC samples via immunohistochemistry.
ATC patients with an abundance of TAMs had a poorer prognosis. Four TAM related genes (FZD6, RBBP8, PREX1, HSD3B7) were identified and a TAM-related prognostic index (TAMRPI) was constructed with high area under the curve (AUC). Next, high TAMRPI was related to the higher level of TAM infiltration and upregulation of several pathways, such as E2F targets, IL6-JAK-STAT3, and G2M checkpoint. Immune checkpoint TIM-3 and CSF1R were positively associated with TAMRPI, and dysfunction of T cells was increased in high TAMRPI subset. Moreover, in the external validation of protein level, strong expression of TAM related genes was related to poorer prognosis, which was further supported by time-dependent AUC analysis.
TAM is negatively correlated to the prognosis of ATC. FZD6, RBBP8, PREX1, and HSD3B7 are potential biomarkers of ATC.
间变性甲状腺癌（ATC）患者的预后非常差。免疫疗法是一种潜在的治疗方法，而目前的结果有限，这可能是由于复杂的肿瘤微环境（TME）所致。肿瘤相关巨噬细胞（TAM）是 ATC 中最丰富的细胞。我们旨在阐明基于 TAM 的 ATC 的新指标。
从基因表达综合数据库（GEO）数据集下载转录组文件。利用加权基因共表达网络分析、Cox 回归、支持向量机和随机森林来识别与 TAM 相关的预后基因。进行共识聚类和主成分分析进行综合分析。此外，通过免疫组织化学对 23 例 ATC 样本进行了复旦大学上海癌症中心队列的外部验证。
TAM 丰富的 ATC 患者预后较差。鉴定出 4 个与 TAM 相关的基因（FZD6、RBBP8、PREX1、HSD3B7），并构建了具有高曲线下面积（AUC）的 TAM 相关预后指数（TAMRPI）。接下来，高 TAMRPI 与 TAM 浸润水平升高和几个途径的上调有关，如 E2F 靶点、IL6-JAK-STAT3 和 G2M 检查点。免疫检查点 TIM-3 和 CSF1R 与 TAMRPI 呈正相关，并且在高 TAMRPI 亚组中 T 细胞功能障碍增加。此外，在蛋白水平的外部验证中，TAM 相关基因的强表达与预后较差相关，这进一步得到了时间依赖性 AUC 分析的支持。
TAM 与 ATC 的预后呈负相关。FZD6、RBBP8、PREX1 和 HSD3B7 是 ATC 的潜在生物标志物。
