胰腺导管内乳头状黏液样腺瘤分子学改变的研究进展  

Research progress in molecular changes of intraductal papillary mucinous neoplasms

作　　者：谢思琦 赵磊[1] 陈振东[1] 王蕊[1] 关景明[1] XIE Siqi;ZHAO Lei;CHEN Zhendong;WANG Rui;GUAN Jingming(Department of Gastroenterology,the Second Affiliated Hospital of Harbin Medical University,Harbin 150086,China)

机构地区：[1]哈尔滨医科大学附属第二医院消化内科,黑龙江哈尔滨150086

出　　处：《胃肠病学和肝病学杂志》2024年第4期463-467,共5页Chinese Journal of Gastroenterology and Hepatology

摘　　要：胰腺囊性肿瘤(pancreatic cystic neoplasms,PCN)是一组异质性囊性肿瘤,包括胰腺导管内乳头状黏液腺瘤(intraductal papillary mucinous neoplasms,IPMN)、黏液性囊性肿瘤(mucinous cystic neoplasms,MCN)、浆液性囊性肿瘤(serous cystic neoplasms,SCN)和其他罕见的囊性病变。其中,IPMN是最常见的一种,和MCN同属于癌前病变。IPMN临床表现各异,包括腹痛、急性胰腺炎、黄疸、糖尿病等,也有无明显症状者。易患因素有胰岛素使用史的糖尿病、慢性胰腺炎和胰腺导管癌(pancreatic ductal carcinoma,PDAC)家族史等。目前常用的检查手段包括影像学、病理学检查等,敏感性和准确性并不高,EUS-FNA取样囊液,对其中脱落囊壁上皮的遗传物质进行下一代靶向基因测序等针对分子学改变的检测准确率高、特异性好。在检测中,KRAS和GNAS突变单独出现或同时出现几乎可在所有IPMN个体中发现。二者分别通过GNAS-PKA-cAMP-SIK和KRAS-PI3K-PIP3-AKT通路影响激素敏感性脂肪酶(hormone-sensitive lipase,HSL)水平,进而细胞的脂质代谢,这可能对肿瘤的启动和维持以及进展浸润起到推进作用。此外,RNF43也在IPMN中发现,推测与泛素E3连接酶作用相关。SMAD4、TP53、PIK3CA、PTEN、KLF4、CDKN2A等也偶可发现,但大部分与高级别异形病变和恶性进展相关。本文阐述了IPMN常发生的突变及其相关可能机制。Pancreatic cystic neoplasms(PCN)is a group of heterogeneous cystic tumors,including intraductal papillary mucinous neoplasms(IPMN),mucinous cystic neoplasms(MCN),serous cystic neoplasms(SCN)and other rare cystic lesions.Among them,IPMN is the most common.IPMN and MCN are both precancerous lesions.The clinical manifestations of IPMN are different,including abdominal pain,acute pancreatitis,jaundice,diabetes and so on.The risk factors include diabetes mellitus with a history of insulin use,chronic pancreatitis and family history of pancreatic ductal carcinoma(PDAC).At present,the sensitivity and accuracy of commonly used examination methods,such as imaging and pathological examination,are not good.EUS-FNA sampling cyst fluid and targeted next generation gene sequencing(NGS)of the genetic material of exfoliated cyst wall epithelium can detect gene mutations with high accuracy and good specificity.KRAS and GNAS mutations can be found in almost all individuals with IPMN alone or together.Both of them affect HSL levels through GNAS-PKA-cAMP-SIK and KRAS-PI3K-PIP3-AKT pathways,and then influence cell lipid metabolism,which may promote tumor initiation and maintenance,as well as invasion.In addition,RNF43 is also found in IPMNs,which is presumably related ubiquitin E3 ligase.SMAD4,TP53,PIK3CA,PTEN,KLF4 and CDKN2A can also be found occasionally,but most of them are related to high-grade abnormal lesions and malignant progression.This paper described the common mutations of IPMN and their possible mechanisms.

关 键 词：胰腺导管内乳头状黏液腺瘤 KRAS GNAS RNF43 胰腺导管腺癌 

分 类 号：R735.7[医药卫生—肿瘤]