Fibroblast Activation Protein-α Expressing Fibroblasts Promote Lymph Node Metastasis in Esophageal Squamous Cell Carcinoma

Onco Targets Ther. 2020 Aug 14:13:8141-8148. doi: 10.2147/OTT.S257529. eCollection 2020.

Abstract

Background and objectives: Esophageal squamous cell carcinoma (ESCC) remains one of the most common malignancies in China and has a high metastasis rate and poor prognosis. Fibroblast activation protein-α (FAP-α) is a serine peptidase the expression of which in cancer-associated fibroblasts has been associated with a higher risk of metastases and poor survival. This study aimed to analyze the correlation of FAP-α expression with the lymph node metastasis and prognostic significance in ESCC.

Methods: FAP-α expression was examined in 121 resected ESCC specimens and 10 adjacent normal tissue using immunohistochemistry. FAP-α expression was scored in the stromal fibroblasts adjacent to neoplastic nests. A chi-square test was used to analyze the correlation between FAP-α expression in tumors stromal and lymph node metastasis of ESCC. The association between FAP-α expression and prognosis was evaluated using univariable and multivariable statistical modeling.

Results: FAP-α expression was absent in the benign controls. FAP-α expression was evident in the stromal 37% (45/121) of ESCC. Expression of FAP-α level is significantly associated with lymph node metastasis (p=0.023), but it is not correlated to age, gender, and tumor location in ESCC patients. Stromal FAP-α expression was significantly associated with poor survival in univariable (HR 2.009; 95% CI 1.259-3.205; p=0.003) and multivariable analysis (HR 1.833; 95% CI 1.144-2.937; p=0.012).

Conclusion: FAP-α may be an important regulator in lymph node metastasis of ESCC and may provide a novel therapeutic target in ESCC.

Keywords: esophageal squamous cell carcinoma; fibroblast activation protein-α; lymph node metastasis; overall survival; prognosis.