Gu Wenchao, Mo Shaocong, Wang Yulin, Kawabata-Iwakawa Reika, Zhang Wei, Yang Zongcheng, Sun Chenyu, Tsushima Yoshito, Xu Huaxiang, Nakajima Takahito
Department of Diagnostic Radiology and Nuclear Medicine, Gunma University Graduate School of Medicine, Maebashi 371-8511, Japan.
Department of Diagnostic and Interventional Radiology, University of Tsukuba, Ibaraki 305-8577, Japan.
Cancers (Basel). 2022 Apr 4;14(7):1825. doi: 10.3390/cancers14071825.
Pancreatic ductal adenocarcinoma (PDAC) is a malignant tumor with a dismal prognosis. PDAC have extensively reprogrammed metabolic characteristics influenced by interactions with normal cells, the effects of the tumor microenvironment and oncogene-mediated cell-autonomous pathways. In this study, we found that among all cancer hallmarks, metabolism played an important role in PDAC. Subsequently, a 16-gene prognostic signature was established with genes derived from crucial metabolic pathways, including glycolysis, bile acid metabolism, cholesterol homeostasis and xenobiotic metabolism (gbcx). The signature was used to distinguish overall survival in multiple cohorts from public datasets as well as a validation cohort followed up by us at Shanghai Cancer Center. Notably, the gbcx-related risk score (gbcxMRS) also accurately predicted poor PDAC subtypes, such as pure-basal-like and squamous types. At the same time, it also predicted PDAC recurrence. The gbcxMRS was also associated with immune cells, especially CD8 T cells, Treg cells. Furthermore, a high gbcxMRS may indicate high drug sensitivity to irinotecan and docetaxel and CTLA4 inhibitor immunotherapy. Taken together, these results indicate a robust and reproducible metabolic-related signature based on analysis of the overall pathogenesis of pancreatic cancer, which may have excellent prognostic and therapeutic implications for PDAC.
胰腺导管腺癌（PDAC）是一种预后极差的恶性肿瘤。PDAC具有广泛重编程的代谢特征，受与正常细胞的相互作用、肿瘤微环境的影响以及癌基因介导的细胞自主通路的作用。在本研究中，我们发现，在所有癌症特征中，代谢在PDAC中起重要作用。随后，利用源自关键代谢途径（包括糖酵解、胆汁酸代谢、胆固醇稳态和外源性物质代谢，即gbcx）的基因建立了一个16基因预后特征。该特征用于区分来自公共数据集的多个队列以及我们在上海癌症中心随访的一个验证队列中的总生存期。值得注意的是，gbcx相关风险评分（gbcxMRS）也准确预测了PDAC的不良亚型，如纯基底样和鳞状类型。同时，它还预测了PDAC的复发。gbcxMRS还与免疫细胞相关，尤其是CD8 T细胞、调节性T细胞。此外，高gbcxMRS可能表明对伊立替康、多西他赛和CTLA4抑制剂免疫疗法具有高药物敏感性。综上所述，这些结果表明基于胰腺癌整体发病机制分析的一个强大且可重复的代谢相关特征，这可能对PDAC具有出色的预后和治疗意义。
