ITGA5 与头颈部鳞状细胞癌的预后标志物和免疫抑制有关。

ITGA5 is associated with prognosis marker and immunosuppression in head and neck squamous cell carcinoma.

机构信息

Department of Head and Neck Surgery, Sichuan Cancer Hospital, Chengdu City, Sichuan Province, China.

Department of Otolaryngology/Head and Neck surgery, People's Hospital of Deyang City, Deyang City, Sichuan Province, China.

出版信息

Diagn Pathol. 2024 Oct 7;19(1):134. doi: 10.1186/s13000-024-01559-1.

DOI:10.1186/s13000-024-01559-1

PMID:39375732

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11457354/

Abstract

BACKGROUND

Head and neck squamous cell carcinoma (HNSCC) is a major tumor that seriously threatens the health of the head and neck or mucosal system. It is manifested as a malignant phenotype of high metastasis and invasion caused by squamous cell transformation in the tissue area. Therefore, it is necessary to search for a biomarker that can systematically correlate and reflect the prognosis of HNSCC based on the characteristics of head and neck tumors.

METHODS

Based on TCGA-HNSCC data, R software was used to analyze gene expression, correlation, Venn diagram, immune invasive and immunosuppressive phenotypes respectively. The intrinsic effect of ITGA5 on the malignant phenotype of HNSCC cells was verified by cell experiments. Immunohistochemical images from The Human Protein Atlas (THPA) database display the differences in the expression of related proteins in HNSCC tissues. Based on functional enrichment and correlation analysis, the prognostic value of ITGA5 for HNSCC was explored, and the expression level of ITGA5 may affect the chemotherapy of targeting the PI3K-AKT.

RESULTS

In this study, the target gene ITGA5 may be identified as a valuable prognostic marker for HNSCC. The results of enrichment analysis showed that ITGA5 was mainly involved in the dynamic process of extracellular matrix, which may affect the migration or metastasis of tumor cells. Meanwhile, ITGA5 may be closely related to the infiltration of M2 macrophages, and its secretory phenotypes TGFB1, PDGFA and PDGFB may affect the immunosuppressive phenotypes of tumor cells, which reflects the systemic influence of ITGA5 in HNSCC. In addition, the expression levels of ITGA5 were negatively correlated with the efficacy of targeting PI3K-AKT chemotherapy.

CONCLUSION

ITGA5 can be used as a potential marker to systematically associate with prognosis of HNSCC, which may be associated with HNSCC malignant phenotype, immunosuppression and chemotherapy resistance.

摘要

背景

头颈部鳞状细胞癌（HNSCC）是一种严重威胁头颈部或黏膜系统健康的主要肿瘤。其表现为组织区域鳞状细胞转化引起的高转移和侵袭的恶性表型。因此，有必要寻找一种生物标志物，能够基于头颈部肿瘤的特征，系统地关联和反映 HNSCC 的预后。

方法

基于 TCGA-HNSCC 数据，使用 R 软件分别进行基因表达、相关性、Venn 图、免疫浸润和免疫抑制表型分析。通过细胞实验验证 ITGA5 对 HNSCC 细胞恶性表型的内在影响。从 The Human Protein Atlas（THPA）数据库的免疫组织化学图像显示 HNSCC 组织中相关蛋白表达的差异。基于功能富集和相关性分析，探讨了 ITGA5 对 HNSCC 的预后价值，ITGA5 的表达水平可能影响针对 PI3K-AKT 的化疗。

结果

本研究中，靶基因 ITGA5 可能被鉴定为 HNSCC 的有价值的预后标志物。富集分析结果表明，ITGA5 主要参与细胞外基质的动态过程，可能影响肿瘤细胞的迁移或转移。同时，ITGA5 可能与 M2 巨噬细胞的浸润密切相关，其分泌表型 TGFB1、PDGFA 和 PDGFB 可能影响肿瘤细胞的免疫抑制表型，这反映了 ITGA5 在 HNSCC 中的系统影响。此外，ITGA5 的表达水平与针对 PI3K-AKT 化疗的疗效呈负相关。