目的:腹膜假黏液瘤(PMP)是一种罕见的临床恶性肿瘤综合征,其特征是大量黏液性腹水在腹膜腔内不可控制地积聚,导致“果冻肚子”。肿瘤进展和粘蛋白高分泌的机制仍然是未知的。但是GNAS突变是一个有前途的因素。本文旨在系统地总结GNAS的生物学背景和变异特征,以及GNAS突变对粘蛋白表达的影响,肿瘤细胞增殖,临床病理特征,和PMP的预后。
方法:使用NCBIPubMed数据库(英文)和WANFANGDATA(中文)进行文献检索。NCBI基因和蛋白质数据库,Ensembl基因组浏览器,COSMIC,UniProt,和RCSBPDB数据库用于基因和蛋白质审查。
结果:GNAS编码鸟嘌呤核苷酸结合蛋白α亚基(Gsα)。PMP中GNAS突变的突变位点相对稳定,通常在Chr20:57,484,420(碱基对:C-G)和Chr20:57,484,421(碱基对:G-C)。典型的GNAS突变导致Gsα中GTP酶活性降低,导致无法水解GTP并释放磷酸,最终GTP与Gsα的连续结合。激活的Gsα可通过刺激cAMP-PKA信号通路持续促进粘蛋白分泌,这是导致PMP粘蛋白分泌增加的可能机制。
结论:GNAS突变是PMP中最重要的分子生物学特征之一,具有促进粘蛋白高分泌的主要功能。
OBJECTIVE: Pseudomyxoma peritonei (PMP) is a rare clinical malignancy syndrome characterized by the uncontrollable accumulation of copious mucinous ascites in the peritoneal cavity, resulting in \"jelly belly\". The mechanism of tumor progression and
mucin hypersecretion remains largely unknown, but GNAS mutation is a promising contributor. This
review is to systemically summarize the biological background and variant features of GNAS, as well as the impacts of GNAS mutations on
mucin expression, tumor cell proliferation, clinical-pathological characteristics, and prognosis of PMP.
METHODS: NCBI PubMed database (in English) and WAN FANG DATA (in Chinese) were used for literature search. And NCBI Gene and Protein databases, Ensembl Genome Browser, COSMIC, UniProt, and RCSB PDB database were used for gene and protein
review.
RESULTS: GNAS encodes guanine nucleotide-binding protein α subunit (Gsα). The mutation sites of GNAS mutation in PMP are relatively stable, usually at Chr20: 57,484,420 (base pair: C-G) and Chr20: 57,484,421 (base pair: G-C). Typical GNAS mutation results in the reduction of GTP enzyme activity in Gsα, causing failure to hydrolyze GTP and release phosphoric acid, and eventually the continuous binding of GTP to Gsα. The activated Gsα could thus continuously promote mucin secretion through stimulating the cAMP-PKA signaling pathway, which is a possible mechanism leading to elevated
mucin secretion in PMP.
CONCLUSIONS: GNAS mutation is one of the most important molecular biological features in PMP, with major functions to promote mucin hypersecretion.