Zhang Jiaqi, Song Shunzhe, Li Yuqing, Gong Aixia
Department of Digestive Endoscopy, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People's Republic of China.
Department of Obstetrics and Gynecology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People's Republic of China.
Cancer Med. 2025 Jan;14(2):e70617. doi: 10.1002/cam4.70617.
Altered glucose metabolism is a critical characteristic from the beginning stage of esophageal squamous cell carcinoma (ESCC), and the phenomenon is presented as a pink-color sign under endoscopy after iodine staining. Therefore, calculating the metabolic score based on the glucose metabolic gene sets may bring some novel insights, enabling the prediction of prognosis and the identification of treatment choices for ESCC.
A total of 8, 99, and 140 individuals from The Gene Expression Omnibus database, The Cancer Genome Atlas database, and the Memorial Sloan Kettering Cancer Center, respectively, were encompassed in the investigation. Patients diagnosed with ESCC after surgery were enrolled for further validation.
A total of 13 kinds of cell clusters were screened, and the squamous epithelium was identified with the highest score. And 558 differential genes were selected from the single-cell RNA sequencing (scRNA-seq) dataset. Four glucose metabolism-related genes, namely, SERP1, CTSC, RAP2B, and SSR4, were identified as hub genes to develop a risk prognostic model. The model was validated in another external cohort. According to the risk score (RS) determined by the model, the patients were categorized into low- and high-risk groups (LRG and HRG). Compared with LRG, HRG indicated poor survival and decreased drug sensitivity. Additionally, the immune microenvironment and pathway enrichment were different between the two groups. Immunohistochemical staining revealed that hub genes were expressed differently in ESCC tissues, high- and low-grade intraepithelial neoplasia, and adjacent normal tissues.
Four hub genes (SERP1, CTSC, RAP2B, and SSR4) screened based on glucose metabolism developed a predictive model in ESCC patients. The RS was established as an independent risk factor for predicting prognosis. These findings may enhance understanding of ESCC's molecular profile and serve as a new prognostic tool for better patient stratification and treatment planning in clinical practice.
糖代谢改变是食管鳞状细胞癌（ESCC）起始阶段的一个关键特征，该现象在内镜碘染色后表现为粉红色征象。因此，基于糖代谢基因集计算代谢评分可能会带来一些新见解，有助于预测ESCC的预后并确定治疗方案。
本研究纳入了分别来自基因表达综合数据库、癌症基因组图谱数据库和纪念斯隆凯特琳癌症中心的8例、99例和140例个体。纳入术后诊断为ESCC的患者进行进一步验证。
共筛选出13种细胞簇，其中鳞状上皮的评分最高。从单细胞RNA测序（scRNA-seq）数据集中筛选出558个差异基因。确定了4个与糖代谢相关的基因，即SERP1、CTSC、RAP2B和SSR4，作为构建风险预后模型的核心基因。该模型在另一个外部队列中得到验证。根据模型确定的风险评分（RS），将患者分为低风险组和高风险组（LRG和HRG）。与LRG相比，HRG的生存率较差且药物敏感性降低。此外，两组之间的免疫微环境和通路富集情况不同。免疫组织化学染色显示，核心基因在ESCC组织、高级别和低级别上皮内瘤变以及相邻正常组织中的表达存在差异。
基于糖代谢筛选出的4个核心基因（SERP1、CTSC、RAP2B和SSR4）在ESCC患者中构建了一个预测模型。RS被确定为预测预后的独立危险因素。这些发现可能会加深对ESCC分子特征的理解，并作为一种新的预后工具，在临床实践中更好地进行患者分层和治疗规划。
