Sun Pingping, Zhang Hui, Shi Jiawen, Xu Manyu, Cheng Tong, Lu Bing, Yang Lei, Zhang Xiaojing, Huang Jianfei
Department of Clinical Biobank, Affiliated Hospital of Nantong University & Medical School of Nantong University, Nantong, Jiangsu 226001, China.
Department of Clinical Biobank, Affiliated Hospital of Nantong University & Medical School of Nantong University, Nantong, Jiangsu 226001, China.
Colloids Surf B Biointerfaces. 2023 Feb;222:113124. doi: 10.1016/j.colsurfb.2023.113124. Epub 2023 Jan 2.
Alterations in protein glycosylation affect tumor progression and immune responses in the tumor microenvironment. Keratinocyte-associated protein 2 (KRTCAP2) encodes the corresponding proteins involved in N-glycosylation. The clinical predictive significance and immune role of KRTCAP2 in hepatocellular carcinoma (HCC) largely remain elusive. Combining bioinformatics tools and multiplex immunohistochemistry analysis, we evaluated the KRTCAP2 expression in the HCC tumor microenvironment. The results showed that KRTCAP2 mRNA and protein expression were markedly increased in HCC tissues. Furthermore, high KRTCAP2 expression was an independent predictive factor of unfavorable prognosis in HCC. Moreover, high KRTCAP2 protein expression was associated with a lower proportion of CD8 T cells and CD68 macrophages in the stroma region. There was also a lower proportion of CD8 T cells in the tumor region with high KRTCAP2 protein expression. Specifically, KRTCAP2 expression showed an inverse relationship with programmed cell death ligand-1 in HCC. Analysis of immunophenoscore showed that the low KRTCAP2 expression group had a stronger ability to predict response to immune checkpoint inhibitors. In conclusion, KRTCAP2 had a significant prognostic value for HCC and was correlated with the immune microenvironment. Our findings suggest that KRTCAP2 is a prognostic marker for HCC patients with potential clinical implications for predicting immunotherapeutic responsiveness.
蛋白质糖基化的改变会影响肿瘤进展以及肿瘤微环境中的免疫反应。角质形成细胞相关蛋白2（KRTCAP2）编码参与N-糖基化的相应蛋白。KRTCAP2在肝细胞癌（HCC）中的临床预测意义和免疫作用在很大程度上仍不清楚。结合生物信息学工具和多重免疫组化分析，我们评估了KRTCAP2在HCC肿瘤微环境中的表达。结果显示，KRTCAP2 mRNA和蛋白表达在HCC组织中显著增加。此外，KRTCAP2高表达是HCC预后不良的独立预测因素。而且，KRTCAP2蛋白高表达与基质区域中CD8 T细胞和CD68巨噬细胞的比例较低相关。在KRTCAP2蛋白高表达的肿瘤区域中，CD8 T细胞的比例也较低。具体而言，KRTCAP2表达在HCC中与程序性细胞死亡配体-1呈负相关。免疫表型评分分析显示，KRTCAP2低表达组预测对免疫检查点抑制剂反应的能力更强。总之，KRTCAP2对HCC具有显著的预后价值，并与免疫微环境相关。我们的研究结果表明，KRTCAP2是HCC患者的预后标志物，对预测免疫治疗反应具有潜在的临床意义。
