Garattini Silvio Ken, Basile Debora, De Re Valli', Brisotto Giulia, Miolo Gianmaria, Canzonieri Vincenzo, Aprile Giuseppe, Corvaja Carla, Buriolla Silvia, Garattini Enrico, Puglisi Fabio
Department of Oncology, ASUFC University Hospital, Udine, Italy.
Department of Medical Oncology, San Giovanni di Dio Hospital, Crotone, Italy.
Front Oncol. 2024 Sep 11;14:1453934. doi: 10.3389/fonc.2024.1453934. eCollection 2024.
Gastric cancer is a heterogeneous collection of tumors characterized by low survival rates. All-trans retinoic acid (retinoic-acid) is a clinically useful therapeutic agent belonging to the chemical family of retinoids, which consists of both natural and synthetic derivatives of vitamin-A. Retinoids are essential components of the normal diet and they regulate different physiological processes. From a therapeutic point of view, retinoic-acid is the first example of clinically useful differentiating agent. Indeed, the differentiating properties of this compound have promoted the use of retinoic-acid as a standard of care in Acute-Promyelocytic-Leukemia, a rare form of acute myeloid leukemia. In this study, we determine the RNA expression of the six isoforms of -- (/////) in view of their potential use as gastric cancer progression markers and/or therapeutic targets. In addition, we evaluate associations between the expression of these receptors and a simplified molecular classification of stomach tumors as well as the clinical characteristics of the cohort of patients analyzed. Finally, we define the prognostic value of the various -- in gastric cancer.
In this single institution and retrospective study, we consider 55 consecutive gastric cancer patients. We extract total RNA from the pathological specimens and we perform a using a customized panel of genes. This allows us to determine the expression levels of the and mRNAs as well as other transcripts of interest.
Our data demonstrate ubiquitous expression of the and mRNAs in gastric cancers. High levels of , , and show a significant association with stage IV tumors, "" metastatic disease, microsatellite-stable-status, epithelial-to-mesenchymal-transition, as well as and expression. Finally, we observe a worse - in gastric cancer patients characterized by high /// mRNA levels.
In gastric cancer, high expression levels of /// transcripts are associated with poor clinical and molecular characteristics as well as with reduced -. Our data are consistent with the idea that , , and represent potential prognostic markers and therapeutic targets of gastric cancer.
胃癌是一组异质性肿瘤，生存率较低。全反式维甲酸（视黄酸）是一种临床有用的治疗药物，属于类视黄醇化学家族，该家族由维生素A的天然和合成衍生物组成。类视黄醇是正常饮食的重要组成部分，它们调节不同的生理过程。从治疗角度来看，视黄酸是临床上有用的分化剂的首个实例。事实上，这种化合物的分化特性促使视黄酸被用作急性早幼粒细胞白血病（一种罕见的急性髓系白血病形式）的标准治疗方法。在本研究中，我们鉴于其作为胃癌进展标志物和/或治疗靶点的潜在用途，确定了——（/////）六种亚型的RNA表达。此外，我们评估了这些受体的表达与胃肿瘤简化分子分类以及所分析患者队列的临床特征之间的关联。最后，我们确定了各种——在胃癌中的预后价值。
在这项单机构回顾性研究中，我们纳入了55例连续的胃癌患者。我们从病理标本中提取总RNA，并使用定制的基因面板进行——。这使我们能够确定——和——mRNA以及其他感兴趣转录本的表达水平。
我们的数据表明，——和——mRNA在胃癌中普遍表达。高水平的——、——、——和——与IV期肿瘤、“”转移疾病、微卫星稳定状态、上皮间质转化以及——和——表达显著相关。最后，我们观察到在以高///mRNA水平为特征的胃癌患者中——更差。
在胃癌中，///转录本的高表达水平与不良的临床和分子特征以及降低的——相关。我们的数据与——、——、——和——代表胃癌潜在预后标志物和治疗靶点的观点一致。
