小柯机器人

复旦大学樊嘉等研究人员合作绘制出肝内胆管癌的蛋白基因组图谱。相关论文于2021年12月30日在线发表在《癌细胞》杂志上。

研究人员利用262名患者的配对肿瘤和邻近的肝脏组织对肝内胆管癌（iCCA）进行了蛋白基因组学特征分析。综合蛋白基因组学分析优先考虑了基因畸变，并揭示了iCCA发病机制的特征。黄曲霉毒素特征与肿瘤的发生、增殖和免疫抑制有关。与突变相关的信号谱显示，TP53和KRAS共同突变可能通过integrin-FAK-SRC途径促进iCCA的转移。FGFR2融合激活了Rho GTP酶途径，可能是新抗原的潜在来源。

蛋白质组分析确定了四个患者亚组（S1-S4），并有亚组特异性生物标志物。这些蛋白质组亚组在预后、基因改变、微环境失调、肿瘤微生物群组成和潜在的治疗方法方面具有明显的特征。SLC16A3和HKDC1被进一步确定为与iCCA细胞的代谢重编程有关的潜在预后生物标志物。

这项研究为研究人员和临床医生提供了宝贵的资源，可用于进一步确定iCCA的分子发病机制和治疗机会。

附：英文原文

Title: Proteogenomic characterization identifies clinically relevant subgroups of intrahepatic cholangiocarcinoma

Author: Liangqing Dong, Dayun Lu, Ran Chen, Youpei Lin, Hongwen Zhu, Zhou Zhang, Shangli Cai, Peng Cui, Guohe Song, Dongning Rao, Xinpei Yi, Yingcheng Wu, Nixue Song, Fen Liu, Yunhao Zou, Shu Zhang, Xiaoming Zhang, Xiaoying Wang, Shuangjian Qiu, Jian Zhou, Shisheng Wang, Xu Zhang, Yongyong Shi, Daniel Figeys, Li Ding, Pei Wang, Bing Zhang, Henry Rodriguez, Qiang Gao, Daming Gao, Hu Zhou, Jia Fan

Issue&Volume: 2021-12-30

Abstract: We performed proteogenomic characterization of intrahepatic cholangiocarcinoma (iCCA)using paired tumor and adjacent liver tissues from 262 patients. Integrated proteogenomicanalyses prioritized genetic aberrations and revealed hallmarks of iCCA pathogenesis.Aflatoxin signature was associated with tumor initiation, proliferation, and immunesuppression. Mutation-associated signaling profiles revealed that TP53 and KRAS co-mutations may contribute to iCCA metastasis via the integrin-FAK-SRC pathway.FGFR2 fusions activated the Rho GTPase pathway and could be a potential source of neoantigens.Proteomic profiling identified four patient subgroups (S1–S4) with subgroup-specificbiomarkers. These proteomic subgroups had distinct features in prognosis, geneticalterations, microenvironment dysregulation, tumor microbiota composition, and potentialtherapeutics. SLC16A3 and HKDC1 were further identified as potential prognostic biomarkersassociated with metabolic reprogramming of iCCA cells. This study provides a valuableresource for researchers and clinicians to further identify molecular pathogenesisand therapeutic opportunities in iCCA.

DOI: 10.1016/j.ccell.2021.12.006

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(21)00659-0

Cancer Cell：《癌细胞》，创刊于2002年。隶属于细胞出版社，最新IF：38.585
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