Yao Guoliang, Zhu Yanfeng, Liu Chunhui, Man Yanwen, Liu Kefeng, Zhang Qin, Tan Yuan, Duan Qianqian, Chen Dongsheng, Du Zunguo, Fan Yonggang
Department of General Surgery, The First Affiliated Hospital of Henan University of Science and Technology, 636 Guanlin Road, Luoyang, China.
Department of Nursing, Huashan Hospital, Fudan University, No.12 Middle Urumqi Road, Shangha, China.
Heliyon. 2024 Jul 30;10(15):e35428. doi: 10.1016/j.heliyon.2024.e35428. eCollection 2024 Aug 15.
Pancreatic ductal adenocarcinoma (PDAC) often presents with liver or peritoneal metastases at diagnosis. Despite similar treatment approaches, patient outcomes vary between these metastatic sites. To improve targeted therapies for metastatic PDAC, a comprehensive analysis of the genetic profiles and evolutionary patterns at these distinct metastatic locations is essential.
We performed whole exome sequencing on 44 tissue samples from 27 PDAC patients, including primary tumours and matched liver or peritoneal metastases. We analysed somatic mutation profiles, signatures, and affected pathways for each group, and examined clonal evolution using subclonal architectures and phylogenetic trees.
mutations remained the predominant driver alteration, with a prevalence of 89 % across all tumours. Notably, we observed site-specific differences in mutation frequencies, with alterations detected in 77.8 % (7/9) of peritoneal metastases and 87.5 % (7/8) of liver metastases. mutations exhibited a similar pattern, occurring in 55.6 % (5/9) of peritoneal and 37.5 % (3/8) of liver metastases. Intriguingly, we identified site-specific alterations in DNA repair pathway genes, including and , with distinct mutational profiles in liver versus peritoneal metastases. Furthermore, liver metastases demonstrated a significantly higher tumor mutational burden (TMB) compared to peritoneal metastases (median [IQR]: 2.14 [1.77-2.71] vs. 1.29 [1.21-1.69] mutations/Mb; P = 0.048).
In conclusion, metastasis of pancreatic cancer may be influenced by variables other than mutations, such as . PDAC peritoneal and liver metastases may differ in potential therapeutic biomarkers. Further inquiry is needed on the biological mechanisms underlying metastasis and the treatment of diverse metastases.
胰腺导管腺癌（PDAC）在诊断时常常伴有肝转移或腹膜转移。尽管采用了相似的治疗方法，但这些转移部位的患者预后各不相同。为了改善转移性PDAC的靶向治疗，对这些不同转移部位的基因图谱和进化模式进行全面分析至关重要。
我们对27例PDAC患者的44个组织样本进行了全外显子测序，包括原发性肿瘤以及匹配的肝转移或腹膜转移样本。我们分析了每组的体细胞突变谱、特征和受影响的通路，并使用亚克隆结构和系统发育树研究了克隆进化。
突变仍然是主要的驱动改变，在所有肿瘤中的发生率为89%。值得注意的是，我们观察到突变频率存在部位特异性差异，在77.8%（7/9）的腹膜转移和87.5%（7/8）的肝转移中检测到改变。突变呈现出类似的模式，发生在55.6%（5/9）的腹膜转移和37.5%（3/8）的肝转移中。有趣的是，我们在DNA修复通路基因中发现了部位特异性改变，包括和，在肝转移与腹膜转移中有不同的突变谱。此外，与腹膜转移相比，肝转移显示出显著更高的肿瘤突变负荷（TMB）（中位数[IQR]：2.14[1.77 - 2.71]与1.29[1.21 - 1.69]个突变/Mb；P = 0.048）。
总之，胰腺癌的转移可能受除突变之外的其他变量影响，如。PDAC的腹膜转移和肝转移在潜在治疗生物标志物方面可能存在差异。需要进一步探究转移的生物学机制以及不同转移灶的治疗方法。
