Department of General Surgery, Affiliated Hospital 6 of Nantong University, Yancheng Third People's Hospital, No. 75, Juchang Road, Yancheng, 224001, China.
Central Laboratory of Yancheng Third People's Hospital, Yancheng, China.
Genes Genomics. 2024 Oct;46(10):1149-1164. doi: 10.1007/s13258-024-01557-z. Epub 2024 Aug 16.
Traditional liquid biopsy markers show a low rate of positivity and accurate in gastric cancer. With the rapid advancement of sequencing technology, scientists have identified promising research avenues in this field. Autophagy and macropinocytosis utilize diverse pathways and mechanisms to supply resources and fuel for tumor growth. Nonetheless, their potential interplay introduces an untapped avenue for the discovery of novel tumor biomarkers.
To develop an innovative prognostic signature based on autophagy- and micropinocytosis-related genes, with the aim to predict the outcome and therapeutic response of gastric cancer patients. Additionally, to validate the prognostic impact of this signature, and elucidate the role of representative molecules in gastric cancer.
To construct and validate a prognostic signature for gastric cancer, bioinformatics methods such as COX regression, LASSO regression, survival analysis, ROC curve, and nomogram were utilized based on the sequencing and clinical data of gastric cancer patients retrieved from the TCGA and GEO databases. GSEA functional enrichment analyses were employed to predict the biological functions. Meanwhile, qRT-PCR and Western blot experiments were utilized to quantify the mRNA and protein expression levels. Furthermore, the EdU assay and colony formation assay were utilized to examine the cell proliferation ability while the Transwell assays were conducted to assess the migration and invasion abilities of gastric cancer cells.
Through consistency clustering and univariate COX analyses, potential prognostic genes involved in both autophagy and macropinocytosis were identified. Based on these genes, a 9-gene signature was constructed, which demonstrated high accuracy in predicting gastric cancer patients' survival period, immunotherapeutic response, and chemotherapy drug tolerance. Furthermore, qRT-PCR analyses of gastric cancer tissue samples showed that the representative genes of this signature were aberrantly overexpressed in gastric cancer, with MATN3, as the most notable molecule, exhibiting significant carcinogenic effects on cancer cells by actively regulating their proliferation, migration, and invasion abilities.
Our newly created prognostic signature possesses significant potential as a biomarker for gastric cancer, while MATN3 is identified as an oncogenic factor in gastric cancer. This brings to light new perspectives, which can contribute to enhancing the diagnosis and treatment of gastric cancer.
传统的液体活检标志物在胃癌中的阳性率较低且准确性不高。随着测序技术的快速发展，科学家们在该领域发现了有前途的研究途径。自噬和巨胞饮作用利用多种途径和机制为肿瘤生长提供资源和燃料。然而，它们潜在的相互作用为发现新的肿瘤生物标志物开辟了一个未开发的途径。
基于自噬和巨胞饮相关基因开发一种创新的预后标志物，旨在预测胃癌患者的预后和治疗反应。此外，验证该标志物的预后影响，并阐明代表性分子在胃癌中的作用。
利用 COX 回归、LASSO 回归、生存分析、ROC 曲线和列线图等生物信息学方法，基于从 TCGA 和 GEO 数据库中检索到的胃癌患者的测序和临床数据，构建和验证用于胃癌的预后标志物。进行 GSEA 功能富集分析以预测生物学功能。同时，使用 qRT-PCR 和 Western blot 实验来定量测定 mRNA 和蛋白质表达水平。此外，通过 EdU 测定和集落形成测定来检测胃癌细胞的增殖能力，通过 Transwell 测定来评估胃癌细胞的迁移和侵袭能力。
通过一致性聚类和单变量 COX 分析，确定了涉及自噬和巨胞饮的潜在预后基因。基于这些基因，构建了一个 9 基因标志物，该标志物在预测胃癌患者的生存期、免疫治疗反应和化疗药物耐受性方面具有很高的准确性。此外，对胃癌组织样本的 qRT-PCR 分析表明，该标志物的代表性基因在胃癌中异常高表达，其中 MATN3 作为最显著的分子，通过积极调节癌细胞的增殖、迁移和侵袭能力，对癌细胞具有显著的致癌作用。
我们新创建的预后标志物具有作为胃癌生物标志物的显著潜力，而 MATN3 被鉴定为胃癌中的致癌因子。这为增强胃癌的诊断和治疗提供了新的视角。
