Expression of VCAN and THBS2 proteins and their relationship with cancer-asso-ciated fibroblasts in papillary thyroid carcinoma
10.13315/j.cnki.cjcep.2025.01.010
- VernacularTitle:甲状腺乳头状癌中VCAN、THBS2蛋白的表达与肿瘤相关成纤维细胞的关系
- Author:
Yintong WU
1
;
Yan FANG
;
Wei PENG
;
Shujing WANG
;
Shan HUANG
;
Xian WANG
;
Hongzhen YU
;
Qiang WU
Author Information
1. 安徽医科大学第二附属医院病理科,合肥 230601
- Publication Type:Journal Article
- Keywords:
thyroid neoplasm;
papillary thyroid carcinoma;
cancer-associated fibroblasts;
VCAN;
THBS2
- From:
Chinese Journal of Clinical and Experimental Pathology
2025;41(1):60-69
- CountryChina
- Language:Chinese
-
Abstract:
Purpose To investigate the expression of Versican(VCAN)and thrombospondin 2(THBS2)and their relationship with cancer-associated fibroblast(CAFs)and clinicopathological significance in papillary thyroid car-cinoma(PTC).Methods Bioinformatics analyses were performed using PTC single-cell sequencing data from the GEO and TCGA database.Weighted correlation network analysis identified CAFs-related genes,and enrichment analy-sis highlighted pivotal genes associated with CAFs;the expression of VCAN,THBS2,and α-SMA in 130 PTC tissue samples were detected by immunohistochemistry EnVision method.Masson staining evaluated tumor stromal fibrosis.Relationships between these markers,clinicopathological parameters,and CAF proliferation were analyzed.Results Bioinformatics analysis identified VCAN and THBS2 as core genes significantly associated with CAFs,and extracellular matrix-related pathways.The proliferation rate of CAFs in PTC was 83.1%(108/130),with positivity rate of 96.9%(126/130)for VCAN and 75.4%(98/130)for THBS2.The median mesenchymal fibrosis index was 32.4(inter-quartile range:22.7-50.0).High CAF proliferation correlated positively with lymph node metastasis(P<0.001),higher TNM stage(P<0.05),and specific histologic subtypes of PTC.Similarly,VCAN expression,THBS2 expres-sion,and the degree of PTC stromal fibrosis were positively correlated with lymph node metastasis(P<0.001,P<0.05,and P<0.001,respectively).Both THBS2 expression and the degree of PTC stromal fibrosis correlated with the histologic subtype of PTC.The percentage of tumor mesenchymal α-SMA-positive cells strongly correlated with the im-mune response score(IRS)of VCAN and THBS2(rs=0.713,P<0.001;rs=0.646,P<0.001).Additionally,the percentage of Masson-stained area was positively correlated with the percentage of tumor mesenchymal α-SMA-posi-tive cells,and the IRS of VCAN and THBS2(rs=0.892,P<0.001;rs=0.729,P<0.001;rs=0.616,P<0.001).Conclusion VCAN and THBS2 serve as potential markers for assessing invasiveness and lymph node metas-tasis of PTC.Their strong association with CAFs provides a basis for further investigation of the malignant biological be-havior of PTC.