Espiau-Romera Pilar, Courtois Sarah, Parejo-Alonso Beatriz, Sancho Patricia
Translational Research Unit, Hospital Universitario Miguel Servet, IIS Aragon, 50009 Zaragoza, Spain.
J Clin Med. 2020 Dec 21;9(12):4128. doi: 10.3390/jcm9124128.
Pancreatic ductal adenocarcinoma (PDAC), the most common form of pancreatic cancer, is an extremely lethal disease due to late diagnosis, aggressiveness and lack of effective therapies. Considering its intrinsic heterogeneity, patient stratification models based on transcriptomic and genomic signatures, with partially overlapping subgroups, have been established. Besides molecular alterations, PDAC tumours show a strong desmoplastic response, resulting in profound metabolic reprogramming involving increased glucose and amino acid consumption, as well as lipid scavenging and biosynthesis. Interestingly, recent works have also revealed the existence of metabolic subtypes with differential prognosis within PDAC, which correlated to defined molecular subclasses in patients: lipogenic subtype correlated with a classical/progenitor signature, while glycolytic tumours associated with the highly aggressive basal/squamous profile. Bioinformatic analyses have demonstrated that the representative genes of each metabolic subtype are up-regulated in PDAC samples and predict patient survival. This suggests a relationship between the genetic signature, metabolic profile, and aggressiveness of the tumour. Considering all this, defining metabolic subtypes represents a clear opportunity for patient stratification considering tumour functional behaviour independently of their mutational background.
胰腺导管腺癌(PDAC)是胰腺癌最常见的形式,由于诊断延迟、侵袭性强以及缺乏有效治疗方法,它是一种极其致命的疾病。考虑到其内在的异质性,已经建立了基于转录组和基因组特征的患者分层模型,这些模型的亚组部分重叠。除了分子改变外,PDAC肿瘤还表现出强烈的促纤维增生反应,导致深刻的代谢重编程,包括葡萄糖和氨基酸消耗增加,以及脂质清除和生物合成。有趣的是,最近的研究还揭示了PDAC中存在预后不同的代谢亚型,这与患者中确定的分子亚类相关:脂肪生成亚型与经典/祖细胞特征相关,而糖酵解肿瘤与高度侵袭性的基底/鳞状特征相关。生物信息学分析表明,每种代谢亚型的代表性基因在PDAC样本中上调,并可预测患者的生存情况。这表明肿瘤的基因特征、代谢谱和侵袭性之间存在关联。考虑到所有这些,考虑肿瘤功能行为而不考虑其突变背景来定义代谢亚型为患者分层提供了一个明确的机会。