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Gastric cancer peritoneal metastasis related signature predicts prognosis and sensitivity to immunotherapy in gastric cancer
Authors:YuQin Sun  YueQing Chen  Wei Zhuang  ShunYong Fang  QiuXian Chen  MingQiao Lian  ChenBin Lv  JianMing Weng  Ran Wei  Yao Lin  LiSheng Cai  QingShui Wang
Institution:1. Department of Gastrointestinal Surgery, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, China

Contribution: Conceptualization (equal), Data curation (equal), Writing - original draft (equal);2. Department of Pathology, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, China

Contribution: Methodology (equal), Resources (equal);3. Department of Urology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China

Contribution: Data curation (equal), Formal analysis (equal);4. Department of Gastrointestinal Surgery, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, China

Contribution: Data curation (equal), ​Investigation (equal);5. Department of Gastrointestinal Surgery, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, China

Contribution: Formal analysis (equal), Methodology (equal);6. Department of Gastrointestinal Surgery, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, China

Contribution: ​Investigation (equal), Methodology (equal);7. Department of Gastrointestinal Surgery, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, China

Contribution: Data curation (equal), Formal analysis (equal);8. Department of Pathology, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, China

Contribution: Methodology (equal), Software (equal);9. Changzhou Key Laboratory of Respiratory Medical Engineering, Institute of Biomedical Engineering and Health Sciences, School of Medical and Health Engineering, Changzhou University, Changzhou, China;10. Central Laboratory at the Second Affiliated Hospital of Fujian University of Traditional Chinese Medical UniversityMedicine, Fujian-Macao Science and Technology Cooperation Base of Traditional Chinese Medicine-Oriented Chronic Disease Prevention and Treatment, Innovation and Transformation Center, Fujian University of Traditional Chinese Medicine, Fuzhou, China;11. Department of Gastrointestinal Surgery, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, China

Abstract:Gastric cancer peritoneal metastases (GCPM) is a leading cause of GC-related death. Early detection of GCPM is critical for improving the prognosis of advanced GC. Differentially expressed genes (DEGs) were identified in the GSE62254 database to distinguish between GCPM and non-GCPM. The gastric cancer peritoneal metastases signature (GCPMs) was developed using DEGs. We analysed the effectiveness of GCPMs as indicators for prognosis, chemotherapy, and immune therapy response in GC patients. Subsequently, we analysed the correlation between GCPMs and immune microenvironment as well as immune escape in GC patients. Random forest model and immunohistochemistry was utilized to identify the crucial genes that can aid in the diagnosis of GCPM. We identified five DEGs and utilized their expression to construct GCPMs. Patients with high GCPMs had a higher likelihood of a poor prognosis, while those with low GCPMs appeared to potentially benefit more from chemotherapy. GCPMs were a dependable marker for predicting the response to immunotherapy. Additionally, GCPMs was found to be significantly linked to stromal score and cancer-associated fibroblasts. SYNPO2 has been identified as the gene with the highest significance in the diagnosis of GCPM. Immunohistochemistry suggests that SYNPO2-positive expression in tumour cells, fibroblasts, inflammatory cell may be associated with promoting peritoneal metastasis in GC. GCPMs have shown to be a promising biomarker for predicting the prognosis and response of GC patients to chemotherapy and immunotherapy. The use of GCPMs for individual tumour evaluation may pave the way for personalized treatment for GC patients in the future.
Keywords:fibroblasts  gastric cancer  immunotherapy  peritoneal metastases  tumour microenvironment
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