PDF(Pubmed)
Abstract：
Integrin β4 (ITGB4) is a member of the integrin family, which plays a crucial role in mediating cell adhesion to the extracellular matrix. Recent studies have demonstrated that ITGB4 is involved in tumorigenesis and metastasis during the development of cancer. However, the role of ITGB4 in oral squamous cell carcinoma (OSCC) remains unclear. A Multiplex immunohistochemistry (OPAL™, mIHC) assay was employed to stain ITGB4, ALDH1, PD-L1, cytokeratin (CK), CD8 and PD-1 in a human OSCC tissue microarray, containing 26 normal oral epithelium samples, 21 oral epithelium dysplasia samples and 76 OSCC samples. The expression pattern and clinicopathological characteristics of ITGB4 were analyzed and compared with those of PD-1, PD-L1, ALDH1 and CD8. The correlation between subgroups of tumor cells, including ITGB4+PD-L1+ and ITGB4+ALDH1+, and subgroups of T cells, including CD8+ and CD8+PD-1+, was evaluated using two-tailed Pearson\'s statistics. A Kaplan-Meier curve was built, and a log-rank test was performed to analyze the survival rate of different subgroups. The mIHC staining results show that ITGB4 was mostly expressed in the tumor cells, with a significant increase in the OSCC specimens compared with normal oral epithelium and oral epithelium dysplasia. The paired analysis, conducted between the OSCC tumor tissue and normal paracancer mucosa, confirmed the results. The study further revealed that ITGB4+PD-L1+ cancer cells, but not ITGB4+ALDH1+ cancer cells, were significantly associated with the infiltration of CD8+ T cells (positivity p = 0.005, positive number p = 0.03). Additionally, ITGB4+PD-L1+ tumor cells were positively correlated with CD8+PD-1+ T cells (positivity p = 0.02, positive number p = 0.03). Most intriguingly, the subgroup of ITGB4/PD-L1high with CD8/PD-1high displayed the best prognosis compared with the other considered subgroups. The results show that the expression of ITGB4 was increased in OSCC compared with normal oral mucosa. Furthermore, a specific subgroup with high levels of expression of ITGB4/PD-L1 and CD8/PD-1 was found to have a relatively better prognosis compared with the other subgroups. Ultimately, this study sheds light on the potential role of ITGB4 in OSCC and provides a basis for further investigation.
摘要：
整合素β4（ITGB4）是整合素家族的成员，在介导细胞与细胞外基质的粘附中起着至关重要的作用。最近的研究表明，ITGB4参与了肿瘤发生和转移过程。然而,ITGB4在口腔鳞状细胞癌(OSCC)中的作用尚不清楚.多重免疫组织化学(OPAL™，mIHC）测定用于染色ITGB4，ALDH1，PD-L1，细胞角蛋白（CK），人类OSCC组织微阵列中的CD8和PD-1，含有26个正常口腔上皮样本，21个口腔上皮发育不良样本和76个OSCC样本。分析ITGB4的表达模式和临床病理特征，并与PD-1，PD-L1，ALDH1和CD8进行比较。肿瘤细胞亚群之间的相关性，包括ITGB4+PD-L1+和ITGB4+ALDH1+，和T细胞亚群，包括CD8+和CD8+PD-1+，使用双尾皮尔森的统计数据进行评估。建立了卡普兰-迈耶曲线，并进行对数秩检验以分析不同亚组的生存率。mIHC染色结果显示，ITGB4大部分在肿瘤细胞中表达，与正常口腔上皮和口腔上皮发育不良相比，OSCC标本显着增加。配对分析，在OSCC肿瘤组织和正常癌旁粘膜之间进行，证实了结果。该研究进一步揭示了ITGB4+PD-L1+癌细胞，但不是ITGB4+ALDH1+癌细胞，与CD8+T细胞浸润显著相关(阳性p=0.005,阳性数量p=0.03)。此外,ITGB4+PD-L1+肿瘤细胞与CD8+PD-1+T细胞呈正相关(阳性p=0.02,阳性数量p=0.03)。最有趣的是，与其他考虑的亚组相比,CD8/PD-1high的ITGB4/PD-L1亚组的预后最佳.结果表明，与正常口腔粘膜相比，OSCC中ITGB4的表达增加。此外，发现ITGB4/PD-L1和CD8/PD-1高表达的特定亚组与其他亚组相比具有相对更好的预后.最终,本研究揭示了ITGB4在OSCC中的潜在作用，为进一步研究提供了依据。
