Comprehensive Analysis of Molecular Biologic Characteristics of Pancreatic Ductal Adenocarcinoma Concomitant with Intraductal Papillary Mucinous Neoplasm
Comprehensive Analysis of Molecular Biologic Characteristics of Pancreatic Ductal Adenocarcinoma Concomitant with Intraductal Papillary Mucinous Neoplasm
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DOI：
10.1245/s10434-022-11704-z
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发表时间：
2022-05-23
影响因子：
3.7
通讯作者：
Kodama, Yuzo
中科院分区：
文献类型：
--
作者：
Tsujimae, Masahiro;Masuda, Atsuhiro;Kodama, Yuzo
背景胰腺导管腺癌（PDAC）伴发导管内乳头状黏液性肿瘤（IPMN）是指胰腺导管腺癌（PDAC）发生于导管内乳头状黏液性肿瘤（IPMN）之外。本研究通过与传统PDAC的比较，全面研究了PDAC合并IPMN在主要遗传学改变、肿瘤微环境和预后方面的分子生物学特征。方法回顾性分析158例经手术切除的PDAC患者的资料。评价了驱动基因改变状态（KRAS、TP 53、CDKN 2A、SMAD 4和GNAS）以及肿瘤中的免疫和纤维化状态。比较PDAC合并IPMN与常规PDAC的预后。结果PDAC联合IPMN治疗组与常规PDAC治疗组在主要驱动基因的改变频率、肿瘤微环境的免疫和纤维化状态方面差异无统计学意义。在倾向匹配的受试者中，接受PDAC联合IPMN治疗的患者与接受常规PDAC治疗的患者之间的总生存期和无病生存期无统计学显著差异。此外，在多变量校正的考克斯比例风险模型中，IPMN的共存不是不良预后因素（风险比，0.95; 95%置信区间，0.51-1.78）。结论在本研究中，PDAC联合IPMN在主要驱动基因改变、肿瘤微环境和预后方面具有与常规PDAC相似的肿瘤特征。
Background Pancreatic ductal adenocarcinoma (PDAC) concomitant with intraductal papillary mucinous neoplasm (IPMN) is defined as PDAC occurring apart from IPMN. This study comprehensively investigated the molecular biologic characteristics of PDAC concomitant with IPMN in major genetic alterations, tumor microenvironment, and prognosis by contrast with those of conventional PDAC. Methods The study retrospectively reviewed the data of 158 surgically resected PDAC patients. The driver gene alteration status (KRAS, TP53, CDKN2A, SMAD4, and GNAS) together with the immune and fibrotic status in tumor was evaluated. The prognosis of PDAC concomitant with IPMN and that of conventional PDAC also were compared. Results No statistically significant difference was found between PDAC concomitant with IPMN and conventional PDAC in the alteration frequency analysis of the major driver genes and the immune and fibrotic status in the tumor microenvironment. Overall survival and disease-free survival between patients who had PDAC concomitant with IPMN and those who had conventional PDAC did not show statistically significant differences in propensity-matched subjects. Furthermore, the co-existence of IPMN was not a poor prognostic factor in the multivariable-adjusted Cox proportional hazards model (hazard ratio, 0.95; 95 % confidence interval, 0.51-1.78). Conclusions In this study, PDAC concomitant with IPMN had tumor characteristics similar to those of conventional PDAC in terms of the major driver gene alterations, tumor microenvironment, and prognosis.