Cancer Management and Research (Oct 2020)
Expression of Integrin β6 and HAX-1 Correlates with Aggressive Features and Poor Prognosis in Esophageal Squamous Cell Carcinoma
Abstract
Fanni Li,1 Yukui Shang,2 Feiyu Shi,3 Lei Zhang,3 Jun Yan,3 Qi Sun,3 Junjun She3 1Department of Talent Highland, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, People’s Republic of China; 2Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084, People’s Republic of China; 3Department of General Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, People’s Republic of ChinaCorrespondence: Qi Sun; Junjun SheDepartment of General Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, 277 Yanta West Road, Xi’an, Shaanxi 710061, People’s Republic of ChinaTel/Fax +86 29 85433720Email [email protected]; [email protected]: The development of esophageal squamous cell carcinoma (ESCC) is a complicated process in which cell adhesion and motility, mediated by integrins, are involved through connecting the cytoskeleton to extracellular matrix. Different mechanisms via which integrin β 6 participates in cancer invasion and metastasis have been described by numerous studies; however, the expression and clinical significance of integrin β 6 in ESCC remain unknown.Methods: To investigate the differential expression of integrin β 6 in ESCC, qPCR and immunohistochemistry assays were performed in 10 paired human samples. A total of 137 ESCC samples were further enrolled to evaluate the expression levels of integrin β 6 and its endocytic trafficking regulator HS1-associated protein X-1 (HAX-1), followed by the evaluation of their correlation with clinicopathological parameters. The overall survival was analyzed using the Kaplan–Meier method, with significant variables further evaluated by multivariate Cox regression analyses.Results: The expression of integrin β 6 was markedly increased in ESCC compared with matched adjacent normal tissues. Among the ESCC samples, positive expression of integrin β 6 was observed in 41.6% tumors, which was associated with histological differentiation, lymph node metastasis and TNM stage. High expression of HAX-1 was detected in 47.4% tumors, and there was a positive relationship between the expression levels of integrin β 6 and HAX-1. Furthermore, the expression of integrin β 6 and HAX-1 were independent unfavorable indicators for prognosis. Patients with positive integrin β 6 and high HAX-1 expression demonstrated worst outcomes.Conclusion: The present findings suggested the predictive value of integrin β 6 and HAX-1 as independent indicators of poor prognosis for patients with ESCC, both of which may contribute to the tumor proliferation and metastasis, leading to ESCC progression. Therefore, combined targeting of integrin β 6 and HAX-1 may provide a potential novel approach for the treatment of ESCC.Keywords: integrin, HAX-1, esophageal squamous cell carcinoma, prognosis
