OncoTargets and Therapy (Aug 2020)

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

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

Journal volume & issue
Vol. Volume 13
pp. 8141 – 8148

Abstract

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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 [email protected]; [email protected] 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

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