Spatially Resolved Niche and Tumor Microenvironmental Alterations in Gastric Cancer Peritoneal Metastases.
Обработка статьи · этапы, ошибки и управление
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Zhao Joseph J, Ong Chin-Ann Johnny, Srivastava Supriya, Chia Daryl Kai Ann, Ma Haoran, Huang Kiekyon, Sheng Taotao, Ramnarayanan Kalpana, Ong Xuewen, Tay Su Ting, Hagihara Takeshi, Tan Angie Lay Keng, Teo Melissa Ching Ching, Tan Qiu Xuan, Ng Gillian, Tan Joey Wee-Shan, Ng Matthew Chau Hsien, Gwee Yong Xiang, Walsh Robert, Law Jia Hao, Shabbir Asim, Kim Guowei, Tay Yvonne, Her Zhisheng, Leoncini Giuseppe, Teh Bin Tean, Hong Jing Han, Tay Ryan Yong Kiat, Teo Chong Boon, Dings Mark P G, Bijlsma Maarten, Lum Jeffrey Huey Yew, Mathur Sachin, Pietrantonio Filippo, Blum Steven M, van Laarhoven Hanneke, Klempner Samuel J, Yong Wei Peng, So Jimmy Bok Yan, Chen Qingfeng, Tan Patrick, Sundar Raghav
Аннотация
METHODS: We conducted a comprehensive multi-omic analysis of 548 samples from 326 patients, including primary tumors, matched normal tissues; peritoneal metastases, and adjacent-normal peritoneal tissues. We used whole exome sequencing, whole transcriptome sequencing, and digital spatial profiling to investigate molecular alterations, gene expression patterns, and TME characteristics associated with PM.
RESULTS: Our analysis identified specific genomic alterations in primary tumors, including mutations in ELF3, CDH1, and PIGR, and TME signatures, such as stromal infiltration and M2 macrophage enrichment, associated with increased risk of PM. We observed distinct transcriptional programs and immune compositions in GCPM compared with liver metastases, highlighting the importance of the TME in transcoelomic metastasis. We found differential expression of therapeutic targets between primary tumors and PM, with lower CLDN18.2 and FGFR2b expression in PM. We unravel the roles of the TME in niche reprogramming within the peritoneum, and provide evidence of pre-metastatic niche conditioning even in early GC without clinical PM. These findings were further validated using a humanized mouse model, which demonstrated niche remodeling in the peritoneum during transcoelomic metastasis.
CONCLUSION: Our study provides a comprehensive molecular characterization of GCPM and unveils key biological principles underlying transcoelomic metastasis. The identified predictive markers, therapeutic targets, and TME alterations offer potential avenues for targeted interventions and improved patient outcomes.