Li Dongbing, Lyu Guizhen
Scientific Research Center, Beijing ChosenMed Clinical Laboratory Co., Ltd. Beijing, 100176, China.
Scientific Research Center, Dongguan Labway Medical Testing Laboratory Co., Ltd., Dongguan, 523429, China.
Curr Med Chem. 2025 May 12. doi: 10.2174/0109298673358646250421023339.
MAX dimerization (MXD) genes play integral roles in various types of tumors. The expression patterns, prognostic value, potential mechanisms, and roles in immunotherapy of MXD genes in gastric cancer (GC) remain not fully elucidated.
We aimed to explore the role of MXDs in GC.
The Wilcoxon rank sum test and t-test were employed to evaluate the differential expression of the MXD gene family members in GC tissues compared to non-paired normal gastric tissues. cBioPortal was utilized for examining genetic alterations within the MXD gene family. R software, specifically version 3.6.3, was used to scrutinize the expression patterns of MXD genes in GC, their correlation with clinical parameters, and to generate a correlation heat map. The survival package (v3.2-10) and the Cox regression model were implemented to evaluate the prognostic significance of the MXD gene family. The pROC package (v1.17.0.1) was applied to assess the diagnostic potential of the MXD gene family. R software (v3.6.3) was also used to explore potential regulatory networks involving members of the MXD gene family and related genes. The GSVA package (v1.34.0) was leveraged to investigate the link between the expression of the MXD gene family and immune cell infiltration. Visualization was facilitated by the ggplot2 (v3.3.3), survminer (v0.4.9), and clusterProfiler (v3.14.3) packages. Gene Set Cancer Analysis (GSCA) was employed to determine the sensitivity of the MXD gene family's expression to drugs from the GDSC database. The expression levels of MXD genes were validated across various cell lines using quantitative real-time PCR (qRT-PCR).
MXD1 was significantly upregulated in GC, while MXD3 and MXD4 were significantly downregulated. Significant correlations were identified between the expression levels of MXD3 and the T stage (p = 0.041) and age (p = 0.001) of GC patients. Additionally, a notable association was observed between MXD4 expression and the histologic grade (p = 0.006) in GC patients. Low MXD3 expression was associated with a poor prognosis in GC. Low MXD3 expression was an independent prognostic factor for poor outcomes in GC patients. MXD3 demonstrated some accuracy in predicting tumor and normal tissue outcomes (AUC = 0.884). MXDs mediate gastric carcinogenesis and progression by regulating immune cells and pathways, including endocytosis, cell cycle, and apoptosis. The expression of the MXD gene family was associated with immune cell infiltration and drug sensitivity. MXD3 and MXD4 expression levels were significantly downregulated in GC cell lines, while MXD1 expression was significantly upregulated.
The MXD gene family may serve as novel biomarkers of poor prognosis and as potential immunotherapeutic targets for GC.
MAX二聚化（MXD）基因在各类肿瘤中发挥着不可或缺的作用。MXD基因在胃癌（GC）中的表达模式、预后价值、潜在机制及在免疫治疗中的作用仍未完全阐明。
我们旨在探究MXD基因在GC中的作用。
采用Wilcoxon秩和检验和t检验评估GC组织中MXD基因家族成员与未配对正常胃组织相比的差异表达。利用cBioPortal检查MXD基因家族内的基因改变。使用R软件（具体版本为3.6.3）来仔细研究GC中MXD基因的表达模式、它们与临床参数的相关性，并生成相关热图。实施生存包（v3.2 - 10）和Cox回归模型来评估MXD基因家族的预后意义。应用pROC包（v1.17.0.1）评估MXD基因家族的诊断潜力。还使用R软件（v3.6.3）探索涉及MXD基因家族成员和相关基因的潜在调控网络。利用GSVA包（v1.34.0）研究MXD基因家族表达与免疫细胞浸润之间的联系。借助ggplot2（v3.3.3）、survminer（v0.4.9）和clusterProfiler（v3.14.3）包进行可视化。采用基因集癌症分析（GSCA）确定MXD基因家族表达对来自GDSC数据库药物的敏感性。使用定量实时PCR（qRT-PCR）在各种细胞系中验证MXD基因的表达水平。
MXD1在GC中显著上调，而MXD3和MXD4显著下调。MXD3的表达水平与GC患者的T分期（p = 0.041）和年龄（p = 0.001）之间存在显著相关性。此外，观察到MXD4表达与GC患者的组织学分级（p = 0.006）之间存在显著关联。低MXD3表达与GC患者的不良预后相关。低MXD3表达是GC患者不良结局的独立预后因素。MXD3在预测肿瘤和正常组织结局方面具有一定准确性（AUC = 0.884）。MXD基因通过调节免疫细胞和途径（包括内吞作用、细胞周期和细胞凋亡）介导胃癌的发生和进展。MXD基因家族的表达与免疫细胞浸润和药物敏感性相关。在GC细胞系中，MXD3和MXD4的表达水平显著下调，而MXD1的表达显著上调。
MXD基因家族可能作为预后不良的新型生物标志物以及GC潜在的免疫治疗靶点。
