Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China.
Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 100021, Beijing, China.
World J Surg Oncol. 2023 Feb 23;21(1):61. doi: 10.1186/s12957-023-02940-y.
Lymph node metastasis (LNM) is an important factor affecting the prognosis of patients with gastric adenocarcinoma (STAD), which is the most common malignancy of the human digestive system. Current detection techniques have limited sensitivity and specificity, and there is a lack of effective biomarkers to screen for LNM. Therefore, it is critical to screen for biomarkers that predict LNM in STAD. Gene expression differential analysis (false discovery rate < 0.05, |logFold change| ≥1.5) was performed on 102 LNM samples, 224 non-LNM samples, and 29 normal gastric tissue samples from The Cancer Genome Atlas (TCGA) STAD dataset, and 269 LNM-specific genes (DEGs) were obtained. Enrichment analysis showed that LNM-specific genes functioned mainly in cytokine-cytokine receptor interactions, calcium signaling, and other pathways. Ten DEGs significantly associated with overall survival in STAD patients were screened by multivariate Cox regression, and an LNM-based 10-mRNA prognostic signature was established (Logrank P < 0.0001). This 10-mRNA signature was well predicted in both the TCGA training set and the Gene Expression Omnibus validation dataset (GSE84437) and was associated with survival in patients with LNM or advanced-stage STAD. Using Kaplan-Meier survival, receiver operating characteristic curve, C-index analysis, and decision curve analysis, the 10-mRNA signature was found to be a more effective predictor of prognosis in STAD patients than the other two reported models (P < 0.0005). Protein-protein interaction network and gene set enrichment analysis of the 10-mRNA signature revealed that the signature may affect the expression of multiple biological pathways and related genes. Finally, the expression levels of prognostic genes in STAD tissues and cell lines were verified using qRT-PCR, Western blot, and the Human Protein Atlas database. Taken together, the prognostic signature constructed in this study may become an indicator for clinical prognostic assessment of LNM-STAD and provide a new strategy for future targeted therapy.
淋巴结转移（LNM）是影响胃腺癌（STAD）患者预后的重要因素，STAD 是人类消化系统最常见的恶性肿瘤。目前的检测技术敏感性和特异性有限，缺乏有效的生物标志物来筛查 LNM。因此，筛选预测 STAD 中 LNM 的生物标志物至关重要。对来自癌症基因组图谱（TCGA）STAD 数据集的 102 个 LNM 样本、224 个非 LNM 样本和 29 个正常胃组织样本进行基因表达差异分析（错误发现率<0.05，|logFold change|≥1.5），获得 269 个 LNM 特异性基因（DEGs）。富集分析表明，LNM 特异性基因主要在细胞因子-细胞因子受体相互作用、钙信号等途径中发挥作用。通过多变量 Cox 回归筛选出与 STAD 患者总生存期显著相关的 10 个 DEG，并建立了基于 LNM 的 10-mRNA 预后特征（Logrank P<0.0001）。该 10-mRNA 特征在 TCGA 训练集和基因表达综合数据库验证数据集（GSE84437）中得到了很好的预测，并与 LNM 或晚期 STAD 患者的生存相关。使用 Kaplan-Meier 生存分析、接收者操作特征曲线、C 指数分析和决策曲线分析，发现 10-mRNA 特征在预测 STAD 患者预后方面比另外两个报道的模型更有效（P<0.0005）。对 10-mRNA 特征的蛋白质-蛋白质相互作用网络和基因集富集分析表明，该特征可能影响多个生物途径和相关基因的表达。最后，使用 qRT-PCR、Western blot 和人类蛋白质图谱数据库验证了 STAD 组织和细胞系中预后基因的表达水平。总之，本研究构建的预后特征可能成为 LNM-STAD 临床预后评估的指标，并为未来的靶向治疗提供新策略。
