胃恶性肿瘤的分子特征

Yuriy A. Gevorkyan, A. Dashkov, N. Soldatkina, V. E. Kolesnikov, N. Timoshkina, D. S. Krutilin, О. К. Bondarenko
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引用次数: 1

摘要

胃癌是最普遍的癌症之一,在全球恶性肿瘤死亡率中占有重要地位。临床症状的晚发是该病常常在晚期诊断的主要原因,这限制了可用的治疗方法。尽管已经开展了广泛的研究,以确定该疾病发生和进展的机制和标志物,但其结果目前尚未完全纳入临床实践。其结果是,长期生存仅取得了微小的改善,患者预后仍然很差。了解胃恶性肿瘤的分子遗传特征,有助于深入了解其发病机制,有助于发现新的预后和诊断生物标志物,并确定新的治疗靶点。近几十年来,高通量测序技术的进步提高了对胃癌分子遗传学方面的认识。本文综述了分子水平的变化,包括肿瘤抑制基因、癌基因、细胞周期和凋亡调节因子、细胞粘附分子、杂合性丧失、微卫星不稳定性和表观遗传畸变(甲基化水平和组蛋白修饰的变化)的信息。本文还从分子层面探讨了胃癌的发病机制——参与胃癌发展的信号通路的变化;本文从分子遗传学的角度对散发性胃癌和遗传性胃癌进行了分类。本文在遗传和表观遗传水平上介绍了胃癌的特点和分类,证实了该病的异质性。这些数据可用于开发和测试潜在的标记物和新的靶向治疗方法。
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Molecular features of malignant gastric tumors
Gastric cancer is one of the most widespread cancers and makes a significant contribution to the global mortality rate from malignant neoplasms. The late onset of clinical symptoms is the main reason why the disease is often diagnosed at an advanced stage, and this limits the available therapeutic approaches. Despite the fact, that extensive studies have been carried out to identify the mechanisms and markers of the development and progression of the disease, their results are currently not fully included in clinical practice. As a consequence, only marginal improvement in long-term survival has been achieved and patient prognosis remains poor. Understanding the molecular genetic features of gastric malignant tumors can provide insight into their pathogenesis, help identify new biomarkers for prognosis and diagnosis, and identify new therapeutic targets. In recent decades, advances in high throughput sequencing technologies have improved understanding of the molecular genetic aspects of gastric cancer. This review considers molecular level changes, including information on tumor suppressor genes, oncogenes, cell cycle and apoptosis regulators, cell adhesion molecules, loss of heterozygosity, micro-satellite instability and epigenetic aberrations (change in methylation level and modification of histones). The review is also devoted to the molecular aspects of pathogenesis – changes in the signaling pathways involved in the gastric cancer development; the classification of sporadic and hereditary gastric cancer at the molecular genetic level is considered. The characteristics and classification of GC presented in this review at the genetic and epigenetic levels confirms that this disease is heterogeneous. These data can be used both to develop and test potential markers and new targeted therapeutic approaches.
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