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Abstract：
BACKGROUND: Papillary thyroid carcinoma (PTC) is globally prevalent and associated with an increased risk of lymph node metastasis (LNM). The role of cancer-associated fibroblasts (CAFs) in PTC remains unclear.
METHODS: We collected postoperative pathological hematoxylin-eosin (HE) slides from 984 included patients with PTC to analyze the density of CAF infiltration at the invasive front of the tumor using QuPath software. The relationship between CAF density and LNM was assessed. Single-cell RNA sequencing (scRNA-seq) data from GSE193581 and GSE184362 datasets were integrated to analyze CAF infiltration in PTC. A comprehensive suite of in vitro experiments, encompassing EdU labeling, wound scratch assays, Transwell assays, and flow cytometry, were conducted to elucidate the regulatory role of CD36+CAF in two PTC cell lines, TPC1 and K1.
RESULTS: A significant correlation was observed between high fibrosis density at the invasive front of the tumor and LNM. Analysis of scRNA-seq data revealed metastasis-associated myoCAFs with robust intercellular interactions. A diagnostic model based on metastasis-associated myoCAF genes was established and refined through deep learning methods. CD36 positive expression in CAFs can significantly promote the proliferation, migration, and invasion abilities of PTC cells, while inhibiting the apoptosis of PTC cells.
CONCLUSIONS: This study addresses the significant issue of LNM risk in PTC. Analysis of postoperative HE pathological slides from a substantial patient cohort reveals a notable association between high fibrosis density at the invasive front of the tumor and LNM. Integration of scRNA-seq data comprehensively analyzes CAF infiltration in PTC, identifying metastasis-associated myoCAFs with strong intercellular interactions. In vitro experimental results indicate that CD36 positive expression in CAFs plays a promoting role in the progression of PTC. Overall, these findings provide crucial insights into the function of CAF subset in PTC metastasis.
METHODS: We collected postoperative pathological hematoxylin-eosin (HE) slides from 984 included patients with PTC to analyze the density of CAF infiltration at the invasive front of the tumor using QuPath software. The relationship between CAF density and LNM was assessed. Single-cell RNA sequencing (scRNA-seq) data from GSE193581 and GSE184362 datasets were integrated to analyze CAF infiltration in PTC. A comprehensive suite of in vitro experiments, encompassing EdU labeling, wound scratch assays, Transwell assays, and flow cytometry, were conducted to elucidate the regulatory role of CD36+CAF in two PTC cell lines, TPC1 and K1.
RESULTS: A significant correlation was observed between high fibrosis density at the invasive front of the tumor and LNM. Analysis of scRNA-seq data revealed metastasis-associated myoCAFs with robust intercellular interactions. A diagnostic model based on metastasis-associated myoCAF genes was established and refined through deep learning methods. CD36 positive expression in CAFs can significantly promote the proliferation, migration, and invasion abilities of PTC cells, while inhibiting the apoptosis of PTC cells.
CONCLUSIONS: This study addresses the significant issue of LNM risk in PTC. Analysis of postoperative HE pathological slides from a substantial patient cohort reveals a notable association between high fibrosis density at the invasive front of the tumor and LNM. Integration of scRNA-seq data comprehensively analyzes CAF infiltration in PTC, identifying metastasis-associated myoCAFs with strong intercellular interactions. In vitro experimental results indicate that CD36 positive expression in CAFs plays a promoting role in the progression of PTC. Overall, these findings provide crucial insights into the function of CAF subset in PTC metastasis.
摘要：
背景：甲状腺乳头状癌（PTC）在全球范围内普遍存在，并且与淋巴结转移（LNM）的风险增加有关。癌症相关成纤维细胞（CAFs）在PTC中的作用尚不清楚。
方法：我们收集984例PTC患者的术后病理苏木精-伊红（HE）切片，使用QuPath软件分析肿瘤浸润前的CAF浸润密度。评估了CAF密度与LNM之间的关系。整合来自GSE193581和GSE184362数据集的单细胞RNA测序(scRNA-seq)数据以分析PTC中的CAF浸润。一套全面的体外实验，包括EdU标签，伤口划痕试验,Transwell分析，和流式细胞术，进行了阐明CD36+CAF在两种PTC细胞系中的调节作用，TPC1和K1。
结果：在肿瘤侵袭性前部的高纤维化密度与LNM之间观察到显着的相关性。对scRNA-seq数据的分析显示，与转移相关的myoCAFs具有强大的细胞间相互作用。通过深度学习方法建立并完善了基于转移相关myoCAF基因的诊断模型。CD36阳性表达可显著促进CAFs的增殖,迁移,和PTC细胞的侵袭能力，同时抑制PTC细胞凋亡。
结论：这项研究解决了PTC中LNM风险的重要问题。对来自大量患者队列的术后HE病理切片的分析显示，肿瘤侵袭性前部的高纤维化密度与LNM之间存在显着关联。整合scRNA-seq数据全面分析PTC中的CAF浸润，鉴定具有强细胞间相互作用的与转移相关的肌CAFs。体外实验结果表明，CAFs中CD36阳性表达对PTC的进展具有促进作用。总的来说,这些发现为CAF亚群在PTC转移中的功能提供了重要见解。
方法：我们收集984例PTC患者的术后病理苏木精-伊红（HE）切片，使用QuPath软件分析肿瘤浸润前的CAF浸润密度。评估了CAF密度与LNM之间的关系。整合来自GSE193581和GSE184362数据集的单细胞RNA测序(scRNA-seq)数据以分析PTC中的CAF浸润。一套全面的体外实验，包括EdU标签，伤口划痕试验,Transwell分析，和流式细胞术，进行了阐明CD36+CAF在两种PTC细胞系中的调节作用，TPC1和K1。
结果：在肿瘤侵袭性前部的高纤维化密度与LNM之间观察到显着的相关性。对scRNA-seq数据的分析显示，与转移相关的myoCAFs具有强大的细胞间相互作用。通过深度学习方法建立并完善了基于转移相关myoCAF基因的诊断模型。CD36阳性表达可显著促进CAFs的增殖,迁移,和PTC细胞的侵袭能力，同时抑制PTC细胞凋亡。
结论：这项研究解决了PTC中LNM风险的重要问题。对来自大量患者队列的术后HE病理切片的分析显示，肿瘤侵袭性前部的高纤维化密度与LNM之间存在显着关联。整合scRNA-seq数据全面分析PTC中的CAF浸润，鉴定具有强细胞间相互作用的与转移相关的肌CAFs。体外实验结果表明，CAFs中CD36阳性表达对PTC的进展具有促进作用。总的来说,这些发现为CAF亚群在PTC转移中的功能提供了重要见解。
