小柯机器人

新加坡国立大学Patrick Tan、Khay Guan Yeoh Jimmy Bok Yan So以及韩国首尔大学Hyunsoo Chung研究组合作发现，肠上皮化生(IM)的时空基因组图谱揭示了胃癌(GC)进展的克隆动力学。2023年10月26日出版的《癌细胞》发表了这项成果。

在一项为期10年的前瞻性研究中，研究人员分析了692名受试者的1256份胃样本(1152份IMs)，确定了26个IM驱动基因，包括染色质调控(ARID1A)和肠道稳态(SOX9)。单细胞和空间剖面突出了组织生态学和IM谱系异质性的变化，包括与早期恶性肿瘤相关的肠干细胞显性细胞室。扩展的转录组分析揭示了IM的基于表达的分子亚型与不完整的组织学、胃/肠细胞类型、ARID1A突变、炎症和通常与健康口腔相关的微生物群落相关。

他们证明，联合临床基因组模型在预测IMs转化为GC的可能性方面优于仅临床模型。通过强调准确识别胃癌高风险IM患者的策略以及微生物生态失调在IM进展中的作用，他们的研究结果为胃癌的精确预防和拦截提供了机会。

据悉，IM是一种与GC风险增加相关的胃粘膜恶性前病变。

附：英文原文

Title: Spatiotemporal genomic profiling of intestinal metaplasia reveals clonal dynamics of gastric cancer progression

Author: Kie Kyon Huang, Haoran Ma, Roxanne Hui Heng Chong, Tomoyuki Uchihara, Benedict Shi Xiang Lian, Feng Zhu, Taotao Sheng, Supriya Srivastava, Su Ting Tay, Raghav Sundar, Angie Lay Keng Tan, Xuewen Ong, Minghui Lee, Shamaine Wei Ting Ho, Tom Lesluyes, Hassan Ashktorab, Duane Smoot, Peter Van Loo, Joy Shijia Chua, Kalpana Ramnarayanan, Louis Ho Shing Lau, Takuji Gotoda, Hyun Soo Kim, Tiing Leong Ang, Christopher Khor, Jonathan Wei Jie Lee, Stephen Kin Kwok Tsao, Wei Lyn Yang, Ming Teh, Hyunsoo Chung, Jimmy Bok Yan So, Khay Guan Yeoh, Patrick Tan

Issue&Volume: 2023-10-26

Abstract: Intestinal metaplasia (IM) is a pre-malignant condition of the gastric mucosa associated with increased gastric cancer (GC) risk. Analyzing 1,256 gastric samples (1,152 IMs) across 692 subjects from a prospective 10-year study, we identify 26 IM driver genes in diverse pathways including chromatin regulation (ARID1A) and intestinal homeostasis (SOX9). Single-cell and spatial profiles highlight changes in tissue ecology and IM lineage heterogeneity, including an intestinal stem-cell dominant cellular compartment linked to early malignancy. Expanded transcriptome profiling reveals expression-based molecular subtypes of IM associated with incomplete histology, antral/intestinal cell types, ARID1A mutations, inflammation, and microbial communities normally associated with the healthy oral tract. We demonstrate that combined clinical-genomic models outperform clinical-only models in predicting IMs likely to transform to GC. By highlighting strategies for accurately identifying IM patients at high GC risk and a role for microbial dysbiosis in IM progression, our results raise opportunities for GC precision prevention and interception.

DOI: 10.1016/j.ccell.2023.10.004

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(23)00360-4

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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