Phosphoproteomic subtyping of gastric cancer reveals dynamic transformation with chemotherapy and guides targeted cancer treatment.

IF 7.5 1区生物学 Q1 CELL BIOLOGY

Cell reports Pub Date : 2024-10-22 Epub Date: 2024-10-01 DOI:10.1016/j.celrep.2024.114774

Hirokazu Shoji, Hidekazu Hirano, Yosui Nojima, Daigo Gunji, Akina Shinkura, Satoshi Muraoka, Yuichi Abe, Ryohei Narumi, Chioko Nagao, Masahiko Aoki, Kazutaka Obama, Kazufumi Honda, Kenji Mizuguchi, Takeshi Tomonaga, Yutaka Saito, Takaki Yoshikawa, Ken Kato, Narikazu Boku, Jun Adachi

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引用次数: 0

Abstract

There are only a few effective molecular targeted agents for advanced unresectable or recurrent advanced gastric cancer (AGC), which has a poor prognosis with a median survival time of less than 14 months. Focusing on phosphorylation signaling in cancer cells, we have been developing deep phosphoproteome analysis from minute endoscopic biopsy specimens frozen within 20 s of collection. Phosphoproteomic analysis of 127 fresh-frozen endoscopic biopsy samples from untreated patients with AGC revealed three subtypes reflecting different cellular signaling statuses. Subsequent serial biopsy analysis has revealed the dynamic mesenchymal transitions within cancer cells, along with the concomitant rewiring of the kinome network, ultimately resulting in the conversion to the epithelial-mesenchymal transition (EMT) subtype throughout treatment. We present our investigation of intracellular signaling related to the EMT in gastric cancer and propose therapeutic approaches targeting AXL. This study also provides a wealth of resources for the future development of treatments and biomarkers for AGC.

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胃癌磷蛋白体亚型分析揭示了化疗的动态转变，并为癌症靶向治疗提供指导。

晚期胃癌（AGC）预后较差，中位生存期不到 14 个月，目前只有少数几种有效的分子靶向药物可用于治疗晚期无法切除或复发的胃癌。我们以癌细胞中的磷酸化信号为研究重点，对采集后 20 秒内冷冻的微小内镜活检标本进行了深度磷酸化蛋白质组分析。对未经治疗的 AGC 患者的 127 份新鲜冷冻内窥镜活检样本进行的磷酸化蛋白质组分析显示，有三种亚型反映了不同的细胞信号状态。随后的连续活检分析揭示了癌细胞内的动态间质转化，以及随之而来的激酶组网络的重新布线，最终导致在整个治疗过程中转化为上皮-间质转化（EMT）亚型。我们介绍了与胃癌 EMT 相关的细胞内信号转导研究，并提出了针对 AXL 的治疗方法。这项研究还为未来开发 AGC 的治疗方法和生物标记物提供了丰富的资源。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cell reports CELL BIOLOGY-

CiteScore

13.80

自引率

1.10%

发文量

1305

审稿时长

77 days

期刊介绍： Cell Reports publishes high-quality research across the life sciences and focuses on new biological insight as its primary criterion for publication. The journal offers three primary article types: Reports, which are shorter single-point articles, research articles, which are longer and provide deeper mechanistic insights, and resources, which highlight significant technical advances or major informational datasets that contribute to biological advances. Reviews covering recent literature in emerging and active fields are also accepted. The Cell Reports Portfolio includes gold open-access journals that cover life, medical, and physical sciences, and its mission is to make cutting-edge research and methodologies available to a wide readership. The journal's professional in-house editors work closely with authors, reviewers, and the scientific advisory board, which consists of current and future leaders in their respective fields. The advisory board guides the scope, content, and quality of the journal, but editorial decisions are independently made by the in-house scientific editors of Cell Reports.