Correlation Of Cancer Associated Fibroblasts With Lymph Node Metastasis In Papillary Thyroid Carcinoma

Objective:To investigate the association between cancer-associated fibroblasts（CAFs）and lymph node metastasis（LNM）in papillary thyroid carcinoma（PTC）by evaluating the expression ofα-smooth muscle actin（α-SMA）-positive CAFs and D2–40-positive lymphatic vessel density（LVD）in PTC tissues and nodular goiter（NG）tissues.Method:Sixty pathological specimens were obtained from patients who underwent surgical resection at The Second Hospital of Jilin University between October 2019 and December 2021.Included were 44 cases of PTC tissues,16 cases of NG tissues.Immunohistochemical analysis was performed to detect the expression levels of the CAFs markerα-SMA and D2–40-positive LVD in PTC and NG tissues.Statistical analysis was used to compare the experimental results of different groups.Result:1.Of the 44 samples of PTC,33 cases（75%）showed the expression ofα-SMA labelled CAFs were positive in the tumor stroma.The expression ofα-SMA labelled CAFs was negative in NG tissues（0%,16 cases）.Statistical difference was found between the two groups（c~2=26.67,p<0.001）.The results of chi-square test showed that the enrichment ofα-SMA positive CAFs was significantly related to lymph node metastasis（c~2=14.87,p<0.001）,but not related to gender,age,tumor size,multifocality,and capsule invasion（p>0.05）.2.The peritumoral LVD in PTC was significantly higher than LVD in NG tissues.Nonparametric testing showed that statistical difference was found between the two groups（p<0.001）.Nonparametric testing revealed a significant correlation between LVD and lymph node metastasis in PTC（p<0.001）.Independent samples t-tests revealed that the level of LVD in PTC was not associated with gender,age,tumor size,multifocality,and capsule invasion（p>0.05）.3.Univariate analysis revealed thatα-SMA positive CAFs and D2–40 positive LVD were important risk factors for lymph node metastasis in PTC（p=0.003,p=0.001）.Multivariate analysis found that D2–40 positive LVD was an independent risk factor for lymph node metastasis in PTC（p=0.041）.4.Independent samples t-tests revealed a significant correlation between high LVD and the enrichment ofα-SMA positive CAFs in PTC（p<0.001）.Conclusion:1.In NG tissues,there was no infiltration ofα-SMA-positive CAFs.The positive area ofα-SMA in PTC stroma suggested thatα-SMA positive CAFs were enriched in PTC stroma.The positive expression rate of CAFs was related to lymph node metastasis,suggesting thatα-SMA positive CAFs may participate in the pathogenesis and development of PTC,and contribute to lymph node metastasis2.The peritumoral LVD in PTC showed a significantly higher LVD than in NG.Higher LVD of PTC tissues showed significantly increased cervical LNM,indicating that lymphangiogenesis may promote the lymph node metastasis of PTC.3.α-SMA-positive CAFs and D2-40-positive LVD were significant risk factors of cervical lymph node metastasis in PTC,but LVD was an independent risk factor of lymph node metastasis in PTC,suggesting thatα-SMA positive CAFs and D2–40positive LVD could be significant predictors of lymph node metastasis in PTC.4.A significant correlation between high LVD and the enrichment ofα-SMA positive CAFs in PTC suggested that CAFs may contribute to lymph node metastasis by involving in the lymphangiogenesis of PTC.