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

 

Authors Li F, Wu X, Sun Z, Cai P, Wu L, Li D

Received 15 April 2020

Accepted for publication 26 July 2020

Published 14 August 2020 Volume 2020:13 Pages 8141—8148

DOI https://doi.org/10.2147/OTT.S257529

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Editor who approved publication: Dr Sanjay Singh

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, prognosis, overall survival