Pu Wen-Feng, Yang Xiao, Wang Xiao-Qing, Guo Xiao-Guang, Yang Mi-Yuan
Department of Gastroenterology, Beijing Anzhen Nanchong Hospital of Capital Medical University and Nanchong Central Hospital, Nanchong 637000, Sichuan Province, China.
College of Pharmacy, Chongqing Medical University, Chongqing 400000, China.
World J Gastrointest Oncol. 2025 Jul 15;17(7):107211. doi: 10.4251/wjgo.v17.i7.107211.
Tumors characterized by high cellular stemness often have unfavorable clinical outcomes, primarily due to their heightened potential for metastasis and resistance to chemotherapy. Among the model genes, the clinical relevance and prognostic significance of Niemann-Pick type C2 (NPC2) in gastric cancer (GC) remained largely unexplored.
To identify stemness-associated genes in GC.
In this study, epithelial cells were categorized as either tumor or normal epithelial cells using the infer copy number variation method. Stemness scores were calculated for both cell types. The hierarchical Weighted Gene Co-expression Network Analysis identified two gene modules with the strongest association with stemness. Prognostically significant stemness-related genes were pinpointed using univariate Cox regression based on The Cancer Genome Atlas dataset. A predictive model related to stemness was constructed using Least Absolute Shrinkage and Selection Operator regression followed by multivariate Cox analysis.
Functional roles of NPC2 were validated using single-cell and bulk RNA sequencing data. Further experimental validation revealed that elevated NPC2 expression promoted tumor cell stemness, invasiveness, migratory ability, and resistance to standard chemotherapeutic agents. Importantly, high NPC2 expression correlated with poorer overall survival in GC patients.
In summary, the proposed model offers prognostic insights that outperform traditional clinical staging and may inform more tailored therapeutic approaches for gastric cancer management.
以高细胞干性为特征的肿瘤通常具有不良的临床结局，主要是因为它们具有更高的转移潜力和对化疗的耐药性。在模型基因中，尼曼-皮克C2型（NPC2）在胃癌（GC）中的临床相关性和预后意义在很大程度上仍未得到探索。
鉴定胃癌中与干性相关的基因。
在本研究中，使用推断拷贝数变异方法将上皮细胞分类为肿瘤上皮细胞或正常上皮细胞。计算两种细胞类型的干性评分。分层加权基因共表达网络分析确定了与干性关联最强的两个基因模块。基于癌症基因组图谱数据集，使用单变量Cox回归确定具有预后意义的干性相关基因。使用最小绝对收缩和选择算子回归，随后进行多变量Cox分析，构建与干性相关的预测模型。
使用单细胞和批量RNA测序数据验证了NPC2的功能作用。进一步的实验验证表明，NPC2表达升高促进了肿瘤细胞的干性、侵袭性、迁移能力以及对标准化疗药物的耐药性。重要的是，NPC2高表达与GC患者较差的总生存期相关。
总之，所提出的模型提供了优于传统临床分期的预后见解，并可能为胃癌管理提供更具针对性的治疗方法。
