口腔鳞状细胞癌中整合素αV和β超家族成员及局灶粘附激酶活性的临床意义:一项回顾性观察研究

S. Sakurai, Y. Ishida, T. Shintani, Sachiko Yamasaki, K. Matsui, T. Hamana, Tadayoshi Nobumoto, Souichi Yanamoto, Y. Hayashido
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摘要

目的:整合素是由α链和β链组成的异源二聚体跨膜质膜蛋白。它们作为 ECM 蛋白受体与细胞外基质(ECM)和细胞骨架蛋白结合。与 ECM 蛋白结合后,整合素会激活局灶粘附激酶(FAK)并传递各种信号。尽管整合素和FAK非常重要,但它们在口腔鳞状细胞癌(OSCC)组织中的表达以及OSCC患者的预后仍然难以确定:在一项回顾性观察研究中,我们对96名OSCC患者的整合素αV、β1、β3、β5、β6、FAK和磷酸化-FAK(pFAK)表达进行了免疫组化评估,并将其作为预后预测指标。根据染色强度将患者分为阳性和阴性两组,并比较两组患者的临床病理特征和存活率。我们还研究了上述整合素相关蛋白与 OSCC 组织中 PD-1 或 PD-L1 之间的关联:结果:我们观察到免疫组化整合素αV、β1、β6、β8和FAK在OSCC组织的细胞膜和细胞质中表达,但整合素β3和β5在OSCC细胞的细胞质中没有表达。与阴性组相比,pFAK阳性的OSCC患者总生存率明显降低,而整合素β8阳性的OSCC患者颈淋巴结转移率明显增加(P<0.05)。在OSCC组织中未观察到整合素相关蛋白与PD-1或PD-L1之间的关联:我们的研究结果表明,pFAK和整合素β8是OSCC的预后因素。因此,以 pFAK 和整合素 β8 为靶点的新型口腔癌诊断和治疗方法具有广阔的前景。
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Clinical significance of integrin αV and β superfamily members and focal adhesion kinase activity in oral squamous cell carcinoma: a retrospective observational study
Objectives: Integrins are heterodimeric transmembrane plasma membrane proteins composed of α- and β-chains. They bind to extracellular matrix (ECM) and cytoskeletal proteins as ECM protein receptors. Upon ECM protein binding, integrins activate focal adhesion kinase (FAK) and transduce various signals. Despite their importance, integrin and FAK expression in oral squamous cell carcinoma (OSCC) tissue and the prognosis of patients with OSCC remains elusive.Methods: In a retrospective observational study, we immunohistochemically evaluated integrin αV, β1, β3, β5, β6, FAK, and phosphorylated-FAK (pFAK) expressions as prognostic predictors in 96 patients with OSCC. Patients were classified as positive or negative based on staining intensity, and clinicopathologic characteristics and survival rates of the two groups were compared. The association between above integrin-related proteins and PD-1 or PD-L1 in OSCC tissues was investigated.Results: We observed immunohistochemical integrin αV, β1, β6, β8, and FAK expressions in the cell membrane and cytoplasm but not integrin β3 and β5 in the OSCC tissues. pFAK was expressed in the cytoplasm of OSCC cells. The overall survival rate significantly decreased in pFAK-positive OSCC patients compared to the negative group, and cervical lymph node metastasis significantly increased in integrin β8-positive patients with OSCC (p < 0.05). No association between integrin-related proteins and PD-1 or PD-L1 in OSCC tissues was observed.Conclusion: Our results indicate that pFAK and integrin β8 are prognostic factors for OSCC. Therefore, pFAK- and integrin β8-targeting new oral cancer diagnostic and therapeutic methods hold a promising potential.
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