Comparative genomic analysis of head and body/tail of pancreatic ductal adenocarcinoma at early and late stages.
Comparative genomic analysis of head and body/tail of pancreatic ductal adenocarcinoma at early and late stages.
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早期和晚期胰腺导管腺癌头体/尾部比较基因组分析
DOI：
10.1111/jcmm.16281
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发表时间：
2021-03
影响因子：
5.3
通讯作者：
Ling Q
中科院分区：
文献类型：
--
作者：
Zhang X;Feng S;Wang Q;Huang H;Chen R;Xie Q;Zhang W;Wang A;Zhang S;Wang L;Yao M;Ling Q
胰腺导管腺癌（Pancreatic ductal adenocarcinoma， PDAC）是人类最致命的癌症之一，在解剖学上可分为头癌和体尾癌。我们之前报道了可切除PDAC中肿瘤位置与预后的相关性。本研究旨在进一步探讨pdac头部和体尾分子多样性的机制。我们使用下一代测序面板检测了154例可切除（手术）和不可切除（活检）的pdac的肿瘤基因组。使用Wilcoxon秩检验或Fisher精确检验来评估两组患者的临床特征、突变频率和生存率之间的关系。与胰头癌相比，胰体/尾癌的KRAS（97.1%比82.4%,P = 0.004）和SMAD4（42.0%比21.2%,P = 0.008）的基因组改变显著增加。在早期阶段（I‐II）， SMAD4在胰体/尾癌中的突变率显著高于胰头癌（56.0% vs 26.5%, P = 0.021）。在晚期（III - IV期），胰腺体/尾癌的KRAS突变率（100.0% vs 75.8%, P = 0.001）、MAPK通路突变频率（100% vs 87.8%, P = 0.040）和可药物基因组改变率（30.8% vs 57.6%, P = 0.030）显著高于胰头癌。我们的工作指出，胰腺体/尾癌在晚期似乎比胰腺头癌更恶性。
Pancreatic ductal adenocarcinoma (PDAC), one of the most lethal human cancers, can be divided into head and body/tail cancers anatomically. We previously reported a prognostic relevance of tumour location in resectable PDAC. This study aimed to further explore the mechanism underlying the molecular diversity between the head and body/tail of PDACs. We detected tumour genomes in 154 resectable (surgery) and non‐resectable (biopsy) PDACs using a next‐generation sequencing panel. Wilcoxon's rank test or Fisher's exact test was used for evaluating associations between clinical characteristics, mutation frequency and survival probability between the two cohorts. Compared with pancreatic head cancers, pancreatic body/tail cancers showed significantly more enriched genomic alterations in KRAS (97.1% vs 82.4%, P = 0.004) and SMAD4 (42.0% vs 21.2%, P = 0.008). At early stages (I‐II), the SMAD4 mutation rate was significantly higher in pancreatic body/tail cancers than pancreatic head cancers (56.0% vs 26.5%, P = 0.021). At late stages (III‐IV), pancreatic body/tail cancers presented significantly higher KRAS mutation rate (100.0% vs 75.8%, P = 0.001), higher frequency of MAPK pathway mutation (100% vs 87.8%, P = 0.040) and lower rates of druggable genomic alterations (30.8% vs 57.6%, P = 0.030) than pancreatic head cancers. Our work points out that pancreatic body/tail cancer seems to be more malignant than pancreatic head cancer at late stages.
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