研究动态
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鉴定自噬和巨胞饮相关的预后特征,用于预测胃癌的预后和治疗反应。

Identification of an autophagy- and macropinocytosis-related prognostic signature for the prediction of prognosis and therapeutic response in gastric cancer.

发表日期:2024 Aug 16
作者: Yuhua Shi, Aifeng Qiu, Hengfeng Cui, Heng Lv, Lei Zhou
来源: Cellular & Molecular Immunology

摘要:

传统的液体活检标志物在胃癌中的阳性率和准确率较低。随着测序技术的快速进步,科学家们在该领域找到了有前途的研究途径。自噬和巨胞饮作用利用不同的途径和机制为肿瘤生长提供资源和燃料。尽管如此,它们潜在的相互作用为发现新型肿瘤生物标志物开辟了一条尚未开发的途径。开发基于自噬和微胞饮相关基因的创新预后特征,旨在预测胃癌患者的结果和治疗反应。此外,为了验证该特征的预后影响,并阐明代表性分子在胃癌中的作用。为了构建和验证胃癌的预后特征,采用COX回归、LASSO回归、生存分析、ROC曲线等生物信息学方法,以及列线图的使用基于从 TCGA 和 GEO 数据库检索的胃癌患者的测序和临床数据。采用GSEA功能富集分析来预测生物学功能。同时,利用qRT-PCR和Western blot实验来定量mRNA和蛋白表达水平。此外,EdU实验和集落形成实验用于检测细胞增殖能力,Transwell实验用于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,发现参与自噬的潜在预后基因和巨胞饮作用被鉴定。基于这些基因,构建了9个基因标签,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表现出较高的准确性。此外,对胃癌组织样本的qRT-PCR分析表明,该特征的代表性基因在胃癌中异常过度表达,其中MATN3作为最显着的分子,通过主动调节癌细胞的增殖、迁移、我们新创建的预后特征具有作为胃癌生物标志物的巨大潜力,而 MATN3 被确定为胃癌的致癌因素。这带来了新的视角,有助于加强胃癌的诊断和治疗。© 2024。作者获得韩国遗传学会的独家许可。
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.© 2024. The Author(s) under exclusive licence to The Genetics Society of Korea.