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整合素α3(ITGA3)和整合素α5(ITGA5)在口腔鳞状细胞癌中的免疫作用及预后价值

Immunological role and prognostic value of ITGA3 and ITGA5 in oral squamous cell carcinoma.

作者信息

Wang Lujuan, Xu Xuemeng, Zeng Deyu, Peng Qiu

机构信息

Hunan Key Laboratory of Tumor Models and Individualized Medicine, The Second Xiangya Hospital, Central South University, Changsha, China.

Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, 283 Tongzipo Road, Changsha, 410013, Hunan, China.

出版信息

Sci Rep. 2025 Aug 17;15(1):30046. doi: 10.1038/s41598-025-16026-0.

Abstract

Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer, originating from the squamous cells of the oral mucosa. The global occurrence is significant and is closely linked to smoking, alcohol use, and HPV infection, with a generally poor prognosis, highlighting the importance of early detection and treatment. Integrins are heterodimeric transmembrane receptors composed of α and β subunits, forming a recognized family of about 24 subtypes. ITGA3 and ITGA5, integrin family members, are crucial for cytoskeletal organization, cell migration, proliferation, and survival. ITGA3 acts as a cell membrane adhesion molecule, engaging with laminin family extracellular matrix proteins linked to tumors. ITGA5 and β1 combine to form a receptor for extracellular fibronectin, playing a role in malignant tumor cells and vasculature. Our study identified that ITGA3 and ITGA5 were overexpressed in oral cancer tissues, correlating with a significantly poorer prognosis for patients exhibiting high levels of these integrins. Further, we found that ITGA3 and ITGA5 were associated with the infiltration of a variety of immune cells as well as with the expression of a variety of immune checkpoints and ferroptosis-related genes. Our findings indicate that ITGA3 and ITGA5 expression levels are associated with the sensitivity to commonly used oral cancer treatments. These findings suggest that ITGA3 and ITGA5 could be potential targets for the prognosis, diagnosis, and treatment of OSCC.

摘要

口腔鳞状细胞癌(OSCC)是最常见的口腔癌类型,起源于口腔黏膜的鳞状细胞。全球发病率很高,与吸烟、饮酒和人乳头瘤病毒(HPV)感染密切相关,总体预后较差,这凸显了早期检测和治疗的重要性。整合素是由α和β亚基组成的异二聚体跨膜受体,构成一个约有24种亚型的公认家族。整合素家族成员ITGA3和ITGA5对细胞骨架组织、细胞迁移、增殖和存活至关重要。ITGA3作为一种细胞膜黏附分子,与与肿瘤相关的层粘连蛋白家族细胞外基质蛋白结合。ITGA5和β1结合形成细胞外纤连蛋白的受体,在恶性肿瘤细胞和脉管系统中发挥作用。我们的研究发现,ITGA3和ITGA5在口腔癌组织中过表达,这与这些整合素水平高的患者预后明显较差相关。此外,我们发现ITGA3和ITGA5与多种免疫细胞的浸润以及多种免疫检查点和铁死亡相关基因的表达有关。我们的研究结果表明,ITGA3和ITGA5的表达水平与常用口腔癌治疗的敏感性相关。这些发现表明,ITGA3和ITGA5可能是口腔鳞状细胞癌预后、诊断和治疗的潜在靶点。

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