Li Fanni, Shang Yukui, Shi Feiyu, Zhang Lei, Yan Jun, Sun Qi, She Junjun
Department of Talent Highland, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, People's Republic of China.
Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084, People's Republic of China.
Cancer Manag Res. 2020 Oct 2;12:9599-9608. doi: 10.2147/CMAR.S274892. eCollection 2020.
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 β6 participates in cancer invasion and metastasis have been described by numerous studies; however, the expression and clinical significance of integrin β6 in ESCC remain unknown.
To investigate the differential expression of integrin β6 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 β6 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.
The expression of integrin β6 was markedly increased in ESCC compared with matched adjacent normal tissues. Among the ESCC samples, positive expression of integrin β6 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 β6 and HAX-1. Furthermore, the expression of integrin β6 and HAX-1 were independent unfavorable indicators for prognosis. Patients with positive integrin β6 and high HAX-1 expression demonstrated worst outcomes.
The present findings suggested the predictive value of integrin β6 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 β6 and HAX-1 may provide a potential novel approach for the treatment of ESCC.
食管鳞状细胞癌（ESCC）的发生发展是一个复杂的过程，其中整合素介导的细胞黏附和运动通过将细胞骨架与细胞外基质相连而参与其中。众多研究描述了整合素β6参与癌症侵袭和转移的不同机制；然而，整合素β6在ESCC中的表达及临床意义仍不清楚。
为研究整合素β6在ESCC中的差异表达，对10对人样本进行了qPCR和免疫组织化学检测。另外纳入137例ESCC样本，评估整合素β6及其内吞转运调节因子HS1相关蛋白X-1（HAX-1）的表达水平，随后评估它们与临床病理参数的相关性。采用Kaplan-Meier法分析总生存期，通过多变量Cox回归分析进一步评估显著变量。
与配对的相邻正常组织相比，ESCC中整合素β6的表达明显增加。在ESCC样本中，41.6%的肿瘤中观察到整合素β6阳性表达，这与组织学分化、淋巴结转移和TNM分期相关。47.4%的肿瘤中检测到HAX-1高表达，整合素β6和HAX-1的表达水平之间存在正相关。此外，整合素β6和HAX-1的表达是预后的独立不良指标。整合素β6阳性且HAX-1高表达的患者预后最差。
目前的研究结果表明，整合素β6和HAX-1作为ESCC患者预后不良独立指标的预测价值，二者均可能促进肿瘤增殖和转移，导致ESCC进展。因此，联合靶向整合素β6和HAX-1可能为ESCC治疗提供一种潜在的新方法。
