诊断学理论与实践 ›› 2022, Vol. 21 ›› Issue (05): 581-587.doi: 10.16150/j.1671-2870.2022.05.006

• 论著 • 上一篇    下一篇

胰腺导管腺癌重要驱动基因突变与临床病理特征、预后间相关性的分析

谢吻, 梁怀予, 董磊, 袁菲, 王朝夫, 郭滟()   

  1. 上海交通大学医学院附属瑞金医院病理科,上海 200025
  • 收稿日期:2020-07-07 出版日期:2022-10-25 发布日期:2023-01-29
  • 通讯作者: 郭滟 E-mail:guoyan@histomed.com
  • 基金资助:
    国家自然科学基金(81500476)

Analysis of genetic status of pivotal driver genes in pancreatic ductal adenocarcinoma and their correlation with clinicopathologic features

XIE Wen, LIANG Huaiyu, DONG Lei, YUAN Fei, WANG Chaofu, GUO Yan()   

  1. Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
  • Received:2020-07-07 Online:2022-10-25 Published:2023-01-29
  • Contact: GUO Yan E-mail:guoyan@histomed.com

摘要:

目的:探讨胰腺导管腺癌(pancreatic ductal adenocarcinoma, PDAC)重要驱动基因突变特点与临床病理特征间的关系。方法:采用靶向测序技术检测269例PDAC患者中相关基因的突变情况,并分析其中重要驱动基因(KRASTP53SMAD4CDKN2A)突变状态与包括年龄、肿瘤分化程度、预后等在内的各项临床病理特征之间的关系。结果:在269例PDAC患者中,KRASTP53SMAD4CDKN2A的突变率分别为82.53%(222/269)、55.02%(148/269)、15.24%(41/269)、11.15%(30/269)。KRAS突变均为错义突变,其中94.59%发生于2号外显子的12位密码子,5.41%则发生于3号外显子的61位密码子。KRAS突变与年龄相关,小于70岁患者中KRAS突变率为80.09%,大于70岁患者中为93.75%(P<0.05);TP53突变与肿瘤分化程度相关,中、高分化患者中TP53突变率为52.52%,低分化患者中为74.19%(P<0.05);SMAD4CDKN2A突变与患者的各项临床病理特征均无关。单因素及多因素生存分析结果显示,TP53突变是影响PDAC患者术后生存的独立危险因素(突变患者的死亡风险为非突变患者的4.3倍)。结论:4种重要驱动基因突变状态中,KRASTP53基因突变状态分别与患者年龄、肿瘤分化程度相关,且TP53突变状态可作为预测PDAC术后患者预后的参考指标。

关键词: 胰腺导管腺癌, 驱动基因, 临床病理特征, 预后

Abstract:

Objective: To investigate the relationship between genetic characteristics of pivotal driver genes and clinicopathological features in pancreatic ductal adenocarcinoma(PDAC). Methods: Mutations in related genes in 269 PDAC patients were detected with targeted sequencing, and the relationship between the genetic status of pivotal driver genes (KRASTP53SMAD4 and CDKN2A) and clinicopathological features (including age, tumor differentiation, and prognosis, etc) were analyzed. Results: Among 269 patients, KRAS, TP53, SMAD4 and CDKN2A mutations were identified in 222 cases (82.53%), 148 cases (55.02%), 41 cases (15.24%) and 30 cases (11.15%) respectively. KRAS mutations were missense mutations, of which 94.59% occurred in codon 12 of exon 2 and 5.41% in codon 61 in exon 3. KRAS mutation might be correlated with age, with a mutation rate of 80.09% in patients younger than 70 years old and 93.75% in patients older than 70 years old (P<0.05); TP53 mutation was correlated with the tumor differentiation, with a mutation rate of 52.52% in well/moderately differentiated patients and 74.19% in poorly differentiated patients (P<0.05); SMAD4 or CDKN2A mutations were not significantly associated with the clinicopathological features. Univariate and multivariate analysis showed that TP53 mutation was an independent risk factor for prognosis of PDAC patients. Conclusions: The genetic status of KRAS and TP53 genes are accociated with the age and tumor differentiation respectively, and TP53 mutation can be used as a reference index to predict the prognosis of PDAC patients.

Key words: Pancreatic ductal adenocarcinoma, Driver gene, Clinicopathological feature, Prognosis

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