Demirkol Canli Secil, Uner Meral, Kucukkaraduman Baris, Karaoglu Diren Arda, Isik Aynur, Turhan Nesrin, Akyol Aytekin, Gomceli Ismail, Gure Ali Osmay
Molecular Pathology Application and Research Center, Hacettepe University, 06100 Ankara, Turkey.
Department of Molecular Biology and Genetics, Bilkent University, 06800 Ankara, Turkey.
Cancers (Basel). 2023 Jun 2;15(11):3035. doi: 10.3390/cancers15113035.
Molecular biomarkers that predict disease progression can help identify tumor subtypes and shape treatment plans. In this study, we aimed to identify robust biomarkers of prognosis in gastric cancer based on transcriptomic data obtained from primary gastric tumors.
Microarray, RNA sequencing, and single-cell RNA sequencing-based gene expression data from gastric tumors were obtained from public databases. Freshly frozen gastric tumors (n = 42) and matched FFPE (formalin-fixed, paraffin-embedded) (n = 40) tissues from a Turkish gastric cancer cohort were used for quantitative real-time PCR and immunohistochemistry-based assessments of gene expression, respectively.
A novel list of 20 prognostic genes was identified and used for the classification of gastric tumors into two major tumor subgroups with differential stromal gene expression ("Stromal-UP" (SU) and "Stromal-DOWN" (SD)). The SU group had a more mesenchymal profile with an enrichment of extracellular matrix-related gene sets and a poor prognosis compared to the SD group. Expression of the genes within the signature correlated with the expression of mesenchymal markers ex vivo. A higher stromal content in FFPE tissues was associated with shorter overall survival.
A stroma-rich, mesenchymal subgroup among gastric tumors identifies an unfavorable clinical outcome in all cohorts tested.
预测疾病进展的分子生物标志物有助于识别肿瘤亚型并制定治疗方案。在本研究中，我们旨在基于原发性胃肿瘤的转录组数据，确定胃癌预后的可靠生物标志物。
从公共数据库中获取基于微阵列、RNA测序和单细胞RNA测序的胃肿瘤基因表达数据。来自土耳其胃癌队列的新鲜冷冻胃肿瘤（n = 42）和匹配的福尔马林固定石蜡包埋（FFPE）（n = 40）组织分别用于基因表达的定量实时PCR和基于免疫组织化学的评估。
确定了一份包含20个预后基因的新列表，并用于将胃肿瘤分为两个具有不同基质基因表达的主要肿瘤亚组（“基质上调”（SU）和“基质下调”（SD））。与SD组相比，SU组具有更多的间充质特征，细胞外基质相关基因集富集，预后较差。特征内基因的表达与体外间充质标志物的表达相关。FFPE组织中较高的基质含量与较短的总生存期相关。
胃肿瘤中富含基质的间充质亚组在所有测试队列中均显示出不良的临床结局。
