Cancer-Associated Fibroblasts Positively Correlate with Dedifferentiation and Aggressiveness of Thyroid Cancer.
Cancer-Associated Fibroblasts Positively Correlate with Dedifferentiation and Aggressiveness of Thyroid Cancer.
复制标题
癌症相关成纤维细胞与甲状腺癌的去分化和侵袭性呈正相关
DOI：
10.2147/ott.s294725
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发表时间：
2021
影响因子：
4
通讯作者：
Ji Q
中科院分区：
文献类型：
--
作者：
Wen S;Qu N;Ma B;Wang X;Luo Y;Xu W;Jiang H;Zhang Y;Wang Y;Ji Q
背景和目的靶向肿瘤相关成纤维细胞（CAF）是一种提高肿瘤治疗效果的方法。CAF在甲状腺乳头状癌（PTC）向去分化甲状腺癌（DDTC）恶变中的作用尚不清楚。本研究旨在探讨CAF与甲状腺癌去分化及临床病理特征的关系。材料与方法我们应用三种不同的基于mRNA的CAF基因标签来定量我们的队列、基因表达综合（GEO）队列和癌症基因组图谱（TCGA）队列中的CAF，并通过免疫组织化学分析甲状腺癌中α-SMA的表达。分析CAF评分与临床病理特征、基因突变、肿瘤相关信号通路和免疫景观的相关性。结果DDTC组织中CAF评分明显高于正常甲状腺组织和PTC组织，α-SMA阳性CAF在DDTC组织中明显富集。DDTC的CAF评分高与间变性表型有关，PTC的CAF评分低与甲状腺分化程度有关。高CAF评分的患者在DDTC和PTC中均显著增加了侵袭性结局的风险。此外，CAF评分与基因突变、致癌信号通路、免疫评分和肿瘤微环境（TME）靶标记物表达增加呈正相关。结论CAFs与甲状腺癌的去分化和侵袭性预后呈正相关，靶向治疗CAFs可能对DDTC患者有益。
Background and Objectives Targeting cancer-associated fibroblast (CAF) is being explored as an approach to improve cancer therapies. The roles of CAF remain unclarified in malignant transformation of papillary thyroid cancer (PTC) into dedifferentiated thyroid cancer (DDTC). This study aimed to investigate correlations of CAF with dedifferentiation and clinicopathological characteristics of thyroid cancer. Materials and Methods We applied three different mRNA-based CAF gene signatures to quantify CAF in our cohort, the Gene Expression Omnibus (GEO) cohort and The Cancer Genome Atlas (TCGA) cohort, and analyzed expression of α-SMA by immunohistochemistry in thyroid cancer. The CAF score was analyzed for its associations with clinicopathological characteristics, genetic mutations, tumor-associated signaling pathways and immune landscape. Results The CAF score increased significantly in DDTCs compared with normal thyroid tissues and PTCs, and the α-SMA-positive CAFs were found enriched in DDTCs. The high CAF score showed a significant correlation with the anaplastic phenotype in DDTC and low thyroid differentiation score in PTC. Patients with a high CAF score remarkably increased the risk of aggressive outcomes in both DDTC and PTC. Furthermore, the CAF score was positively correlated with genetic mutations, oncogenic signaling pathways, the immune score and increased expression of tumor microenvironment (TME) target markers. Conclusion Our findings suggest CAFs positively correlate with dedifferentiation and aggressive outcomes of thyroid cancer, and targeting CAFs as a therapeutic approach may benefit DDTC patients.