Integrated analysis of fibroblasts molecular features in papillary thyroid cancer combining single-cell and bulk RNA sequencing technology

BackgroundPapillary 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 d...

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Main Authors: Wei Li, Zhiyong Liu, Xiaoxia Cen, Jing Xu, Suo Zhao, Bin Wang, Wei Zhang, Ming Qiu
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-10-01
Series:Frontiers in Endocrinology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fendo.2022.1019072/full
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author Wei Li
Zhiyong Liu
Xiaoxia Cen
Jing Xu
Suo Zhao
Bin Wang
Wei Zhang
Ming Qiu
author_facet Wei Li
Zhiyong Liu
Xiaoxia Cen
Jing Xu
Suo Zhao
Bin Wang
Wei Zhang
Ming Qiu
author_sort Wei Li
collection DOAJ
description BackgroundPapillary 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.MethodsSingle-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.ResultsFibroblasts 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.ConclusionOur research demonstrated a comprehensive horizon of fibroblasts features in thyroid cancer microenvironment, which may provide potential value for thyroid cancer treatment.
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spelling doaj.art-535e72d7fb584c61acc46e5ba5155a3f2022-12-22T02:35:42ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922022-10-011310.3389/fendo.2022.10190721019072Integrated analysis of fibroblasts molecular features in papillary thyroid cancer combining single-cell and bulk RNA sequencing technologyWei Li0Zhiyong Liu1Xiaoxia Cen2Jing Xu3Suo Zhao4Bin Wang5Wei Zhang6Ming Qiu7Department of General Surgery, Changzheng Hospital, Navy Medical University, Shanghai, ChinaDepartment of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai, ChinaDepartment of General Surgery, Changzheng Hospital, Navy Medical University, Shanghai, ChinaDepartment of General Surgery, Changzheng Hospital, Navy Medical University, Shanghai, ChinaDepartment of General Surgery, Changzheng Hospital, Navy Medical University, Shanghai, ChinaDepartment of General Surgery, Changzheng Hospital, Navy Medical University, Shanghai, ChinaDepartment of General Surgery, Changzheng Hospital, Navy Medical University, Shanghai, ChinaDepartment of General Surgery, Changzheng Hospital, Navy Medical University, Shanghai, ChinaBackgroundPapillary 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.MethodsSingle-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.ResultsFibroblasts 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.ConclusionOur research demonstrated a comprehensive horizon of fibroblasts features in thyroid cancer microenvironment, which may provide potential value for thyroid cancer treatment.https://www.frontiersin.org/articles/10.3389/fendo.2022.1019072/fullthyroid cancersingle-cell sequencingtumor environmentfibroblastsprognosis
spellingShingle Wei Li
Zhiyong Liu
Xiaoxia Cen
Jing Xu
Suo Zhao
Bin Wang
Wei Zhang
Ming Qiu
Integrated analysis of fibroblasts molecular features in papillary thyroid cancer combining single-cell and bulk RNA sequencing technology
Frontiers in Endocrinology
thyroid cancer
single-cell sequencing
tumor environment
fibroblasts
prognosis
title Integrated analysis of fibroblasts molecular features in papillary thyroid cancer combining single-cell and bulk RNA sequencing technology
title_full Integrated analysis of fibroblasts molecular features in papillary thyroid cancer combining single-cell and bulk RNA sequencing technology
title_fullStr Integrated analysis of fibroblasts molecular features in papillary thyroid cancer combining single-cell and bulk RNA sequencing technology
title_full_unstemmed Integrated analysis of fibroblasts molecular features in papillary thyroid cancer combining single-cell and bulk RNA sequencing technology
title_short Integrated analysis of fibroblasts molecular features in papillary thyroid cancer combining single-cell and bulk RNA sequencing technology
title_sort integrated analysis of fibroblasts molecular features in papillary thyroid cancer combining single cell and bulk rna sequencing technology
topic thyroid cancer
single-cell sequencing
tumor environment
fibroblasts
prognosis
url https://www.frontiersin.org/articles/10.3389/fendo.2022.1019072/full
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