小柯机器人

韩国国立癌症中心Jong Bae Park等研究人员合作揭示胶质母细胞瘤演化的综合蛋白质组学特征。相关论文于2024年1月11日在线发表在《癌细胞》杂志上。

研究人员对123对纵向胶质母细胞瘤进行了综合蛋白质基因组学分析，确定了诊断时高度增殖的细胞状态，以及复发性肿瘤中神经元过渡和突触生成通路的激活所取代的细胞状态。蛋白质组和磷酸化蛋白质组分析表明，复发时向神经元状态的分子转变以无翼鸟相关整合位点（WNT）/平面细胞极性（PCP）信号通路和BRAF蛋白激酶的翻译后激活为标志。

对患者衍生异种移植物（PDX）模型的多组学分析也反映了类似的演化轨迹。抑制B-raf原癌基因（BRAF）激酶会损害复发性肿瘤细胞的神经元转换和迁移能力，这是治疗后进展的表型特征。替莫唑胺（TMZ）与BRAF抑制剂维罗非尼的联合治疗可显著延长PDX模型的生存期。这项研究全面揭示了胶质母细胞瘤演变和耐药的生物学机制，为临床干预提供了有前景的治疗策略。

据悉，胶质母细胞瘤（GBM）的演化轨迹是一个多方面的生物学过程，不仅仅是基因改变。

附：英文原文

Title: Integrated proteogenomic characterization of glioblastoma evolution

Author: Kyung-Hee Kim, Simona Migliozzi, Harim Koo, Jun-Hee Hong, Seung Min Park, Sooheon Kim, Hyung Joon Kwon, Seokjun Ha, Luciano Garofano, Young Taek Oh, Fulvio DAngelo, Chan Il Kim, Seongsoo Kim, Ji Yoon Lee, Jiwon Kim, Jisoo Hong, Eun-Hae Jang, Bertrand Mathon, Anna-Luisa Di Stefano, Franck Bielle, Alice Laurenge, Alexey I. Nesvizhskii, Eun-Mi Hur, Jinlong Yin, Bingyang Shi, Youngwook Kim, Kyung-Sub Moon, Jeong Taik Kwon, Shin Heon Lee, Seung Hoon Lee, Ho Shin Gwak, Anna Lasorella, Heon Yoo, Marc Sanson, Jason K. Sa, Chul-Kee Park, Do-Hyun Nam, Antonio Iavarone, Jong Bae Park

Issue&Volume: 2024-01-11

Abstract: The evolutionary trajectory of glioblastoma (GBM) is a multifaceted biological processthat extends beyond genetic alterations alone. Here, we perform an integrative proteogenomicanalysis of 123 longitudinal glioblastoma pairs and identify a highly proliferativecellular state at diagnosis and replacement by activation of neuronal transition andsynaptogenic pathways in recurrent tumors. Proteomic and phosphoproteomic analysesreveal that the molecular transition to neuronal state at recurrence is marked bypost-translational activation of the wingless-related integration site (WNT)/ planarcell polarity (PCP) signaling pathway and BRAF protein kinase. Consistently, multi-omicanalysis of patient-derived xenograft (PDX) models mirror similar patterns of evolutionarytrajectory. Inhibition of B-raf proto-oncogene (BRAF) kinase impairs both neuronaltransition and migration capability of recurrent tumor cells, phenotypic hallmarksof post-therapy progression. Combinatorial treatment of temozolomide (TMZ) with BRAFinhibitor, vemurafenib, significantly extends the survival of PDX models. This studyprovides comprehensive insights into the biological mechanisms of glioblastoma evolutionand treatment resistance, highlighting promising therapeutic strategies for clinicalintervention.

DOI: 10.1016/j.ccell.2023.12.015

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(23)00443-9

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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