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

• Main Authors: Li F, Wu X, Sun Z, Cai P, Wu L, Li D
• Format: Article
• Language: English
• Published: Dove Medical Press 2020-08-01
• Series: OncoTargets and Therapy
• Subjects: esophageal squamous cell carcinoma; fibroblast activation protein-α; lymph node metastasis; prognosis; overall survival
• Online Access: https://www.dovepress.com/fibroblast-activation-protein-alpha-expressing-fibroblasts-promote-lym-peer-reviewed-article-OTT

Feng Li,1,* Xia Wu,2,* Zhixiang Sun,3,* Peng Cai,1 Ligao Wu,2 Duojie Li1 1Department of Radiotherapy, First Affiliated Hospital of Bengbu Medical College, Bengbu 233000, People’s Republic of China; 2Department of Pathology, First Affiliated Hospital of Bengbu Medical College, Bengbu 233000, People’s Republic of China; 3Department of Neurosurgery, First Affiliated Hospital of Bengbu Medical College, Bengbu 233000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ligao Wu; Duojie Li Email [e-mail]; [e-mail] 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