AUTHOR=Li Wei , Liu Zhiyong , Cen Xiaoxia , Xu Jing , Zhao Suo , Wang Bin , Zhang Wei , Qiu Ming TITLE=Integrated analysis of fibroblasts molecular features in papillary thyroid cancer combining single-cell and bulk RNA sequencing technology JOURNAL=Frontiers in Endocrinology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2022.1019072 DOI=10.3389/fendo.2022.1019072 ISSN=1664-2392 ABSTRACT=Background

Papillary thyroid cancer (PTC) is the most common pathological type of thyroid cancer with a high incidence globally. Increasing evidence reported that fibroblasts infiltration in cancer was correlated with prognostic outcomes. However, fibroblasts related study in thyroid cancer remains deficient.

Methods

Single-cell sequencing data of PTC were analyzed by Seurat R package to explore the ecosystem in PTC and identify fibroblasts cluster. The expression profiles and prognostic values of fibroblast related genes were assessed in TCGA dataset. A fibrosis score model was established for prognosis prediction in thyroid cancer patients. Differentially expressed genes and functional enrichment between high and low fibrosis score groups in TCGA dataset were screened. The correlation of immune cells infiltration and fibrosis score in thyroid cancer patients was explored. Expression levels and prognostic values of key fibroblast related factor were validated in clinical tissues another PTC cohort.

Results

Fibroblasts were highly infiltrated in PTC and could interact with other type of cells by single-cell data analysis. 34 fibroblast related terms were differentially expressed in thyroid tumor tissues. COX regression analysis suggested that the constructed fibrosis score model was an independent prognostic predictor for thyroid cancer patients (HR = 5.17, 95%CI 2.31-11.56, P = 6.36E-05). Patients with low fibrosis scores were associated with a significantly better overall survival (OS) than those with high fibrosis scores in TCGA dataset (P = 7.659E-04). Specific immune cells infiltration levels were positively correlated with fibrosis score, including monocytes, M1 macrophages and eosinophils.

Conclusion

Our research demonstrated a comprehensive horizon of fibroblasts features in thyroid cancer microenvironment, which may provide potential value for thyroid cancer treatment.