Zhong Mingyang, Yu Zhuoqun, Wu Qianqian, Lu Bing, Sun PingPing, Zhang Xiaojing, Yang Lei, Wu Han
Department of General Surgery, Medical School of Nantong University, & Department of Gastrointestinal Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China.
Clinical and Translational Research Center & Institute of Oncology, Affiliated Hospital of Nantong University, Department of Oncology, Medical School of Nantong University, Nantong, Jiangsu, China.
Front Immunol. 2024 Dec 2;15:1500478. doi: 10.3389/fimmu.2024.1500478. eCollection 2024.
Gastric cancer (GC) is one of the most common malignant tumors and is associated with poor prognosis. To improve the prognosis of GC patients, an effective immune-related prognostic biomarker is urgent. Here, we aim to explore the correlation between the expression of procalcitonin gamma subfamily A, 10 (PCDHGA10) and clinicopathological characteristics, especially its relation with tumor-infiltrating immune cells (TILs) in GC.
The differential mRNA expression of PCDHGA10 between GC tissues and normal gastric mucosa and prognostic potential were assessed from The Cancer Genome Atlas (TCGA). Then, based on tissue microarrays (TMAs) with multiplex immunohistochemistry (mIHC) from GC patients, we statistically assess the correlation between PCDHGA10 protein expression and the clinical profiles and prognosis of the patients. Additionally, with IHC and mIHC, we applied the machine-learning algorithms to evaluate the localization and expression levels of TILs and immune checkpoints in the tumor microenvironment. We analyzed the relationship between PCDHGA10 protein expression and TILs and immune checkpoints.
Through the database and TMA analysis, the expression of PCDHGA10 was significantly higher in GC tissues compared with normal tissues. High PCDHGA10 expression independently predicted poor prognosis in GC. Additionally, elevated PCDHGA10 expression was positively associated with the number of CD8 T cells, CD68 macrophages, Foxp3 T cells, and CD4 T cells in GC tissues and the stromal region. Besides, the expression of PCDHGA10 was positively correlated with immune checkpoints, including CTLA-4, LAG3, and PD-L1.
PCDHGA10 might be a potential prognostic marker and an immunological therapeutic target for GC.
胃癌（GC）是最常见的恶性肿瘤之一，预后较差。为改善GC患者的预后，急需一种有效的免疫相关预后生物标志物。在此，我们旨在探讨原钙黏蛋白γ A亚家族10（PCDHGA10）的表达与临床病理特征之间的相关性，尤其是其与GC中肿瘤浸润免疫细胞（TILs）的关系。
从癌症基因组图谱（TCGA）评估GC组织和正常胃黏膜之间PCDHGA10的差异mRNA表达及预后潜力。然后，基于GC患者的组织芯片（TMAs）和多重免疫组化（mIHC），我们统计学评估PCDHGA10蛋白表达与患者临床特征及预后之间的相关性。此外，通过免疫组化（IHC）和mIHC，我们应用机器学习算法评估肿瘤微环境中TILs和免疫检查点的定位及表达水平。我们分析了PCDHGA10蛋白表达与TILs和免疫检查点之间的关系。
通过数据库和TMA分析，与正常组织相比，GC组织中PCDHGA10的表达显著更高。高PCDHGA10表达独立预测GC患者预后不良。此外，GC组织和基质区域中PCDHGA10表达升高与CD8 T细胞、CD68巨噬细胞、Foxp3 T细胞和CD4 T细胞数量呈正相关。此外，PCDHGA10的表达与免疫检查点，包括CTLA-4、LAG3和PD-L1呈正相关。
PCDHGA10可能是GC的潜在预后标志物和免疫治疗靶点。
