Yang Yu-Ping, Bai Min, Cheng Yin-Xia, Feng Xin, Zhang Yan-Ying, Zhang Yuan-Yuan, Liu Meng-Ya, Duan Yong-Qiang
Gansu University of Traditional Chinese Medicine, College of Basic Medical Sciences, Lanzhou, 730000, PR China.
Ningxia Medical University, College of Traditional Chinese Medicine, Yinchuan, 750000, PR China.
Heliyon. 2024 Mar 16;10(7):e27362. doi: 10.1016/j.heliyon.2024.e27362. eCollection 2024 Apr 15.
Primary liver cancer (PLC) is a prevalent malignancy of the digestive system characterized by insidious symptom onset and a generally poor prognosis. Recent studies have highlighted a significant correlation between the initiation and prognosis of liver cancer and the immune function of PLC patients.
Revealing the expression of PLC-related immune genes and the characteristics of immune cell infiltration provides assistance for the analysis of clinical pathological parameters and prognosis of PLC patients.
PLC-related differentially expressed genes (DEGs) with a median absolute deviation (MAD > 0.5) were identified from TCGA and GEO databases. These DEGs were intersected with immune-related genes (IRGs) from the ImmPort database to obtain PLC-related IRGs. The method of constructing a prognostic model through immune-related gene pairs (IRGPs) is used to obtain IRGPs and conduct the selection of central immune genes. The central immune genes obtained from the selection of IRGPs are validated in PLC. Subsequently, the relative proportions of 22 types of immune cells in different immune risk groups are evaluated, and the differential characteristics of PLC-related immune cells are verified through animal experiments.
Through database screening and the construction of an IRGP prognosis model, 84 pairs of IRGPs ( < 0.001) were ultimately obtained. Analysis of these 84 IRGPs revealed 11 central immune genes related to PLC, showing differential expression in liver cancer tissues compared to normal liver tissues. Results from the CiberSort platform indicate differential expression of immune cells such as naive B cells, macrophages, and neutrophils in different immune risk groups. Animal experiments demonstrated altered immune cell proportions in H22 tumor-bearing mice, validating findings from peripheral blood and spleen homogenate analyses.
Our study successfully predicted and validated PLC-related IRGs and immune cells, suggesting their potential as prognostic indicators and therapeutic targets for PLC.
原发性肝癌(PLC)是消化系统常见的恶性肿瘤,其症状隐匿,预后通常较差。最近的研究强调了肝癌的发生和预后与PLC患者免疫功能之间的显著相关性。
揭示PLC相关免疫基因的表达及免疫细胞浸润特征,为分析PLC患者的临床病理参数和预后提供帮助。
从TCGA和GEO数据库中鉴定出中位数绝对偏差(MAD>0.5)的PLC相关差异表达基因(DEG)。将这些DEG与ImmPort数据库中的免疫相关基因(IRG)进行交叉分析,以获得PLC相关的IRG。采用通过免疫相关基因对(IRGP)构建预后模型的方法来获得IRGP并进行核心免疫基因的筛选。从IRGP筛选中获得的核心免疫基因在PLC中进行验证。随后,评估不同免疫风险组中22种免疫细胞的相对比例,并通过动物实验验证PLC相关免疫细胞的差异特征。
通过数据库筛选和构建IRGP预后模型,最终获得84对IRGP(<0.001)。对这84对IRGP的分析揭示了11个与PLC相关的核心免疫基因,与正常肝组织相比,这些基因在肝癌组织中表现出差异表达。CiberSort平台的结果表明,不同免疫风险组中幼稚B细胞、巨噬细胞和中性粒细胞等免疫细胞存在差异表达。动物实验表明,荷H22肿瘤小鼠的免疫细胞比例发生了变化,验证了外周血和脾匀浆分析的结果。
我们的研究成功预测并验证了PLC相关的IRG和免疫细胞,表明它们作为PLC预后指标和治疗靶点的潜力。