Peritoneal Metastasis of Gastric Cancer: From Basic Research to Clinical Application

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About this Research Topic

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Background

Gastric cancer (GC) is one of the leading causes of cancer-related deaths worldwide, and the 5-year survival rate is only 20%-40%. Peritoneal metastasis is the most common and important prognostic factor of advanced gastric cancer. Previous studies reported that about 20% of the patients with gastric cancer were diagnosed with peritoneal metastases (PM) preoperatively or intraoperatively, and over 50% of T3/T4 GC patients appear PM after radical resection. According to statistics, the median overall survival of these patients is only 15.6 months, even though they received aggressive treatment.

PM is a complicated biological process involving detachment from the primary tumor, seeding and survival with the cavum abdominis, adhesion to the peritoneum, invasion through the basement membrane to sub-peritoneal tissue, and proliferation with blood vascular neogenesis. Epithelial–mesenchymal transition (EMT) is essential for epithelial-derived malignant tumor cells to acquire the ability of migration and invasion; and cellular stemness can effectively suppress anoikis of free GC cells in the abdominal cavity and promote colonization in the peritoneal milky spots.

In recent years, intercellular crosstalk between tumor and microenvironment is the research focus of PM. “Seed-and-soil” hypothesis is highly approved by scientists. Gastric cancer cells could induce fibrosis and apoptosis of mesothelial cells, and the CXCL12 and CXCL16 chemokines released by the damaged mesothelial cells enhanced the ability of adhesion and invasion of cancer cells. In the last decade, exosomes have been identified as contributors to PM. GC-derived exosomes can remodel the premetastatic microenvironment by destroying mesothelial barriers, and then promote PM of GC. More precise mechanisms need to be further studied.

Conventional imaging technique is limited for diagnosis of PM in GC patients. Some invasive tests, such as intraperitoneal free cancer cells (cytology, CY) and diagnostic laparoscopy, are recommended for guiding therapeutic strategy of PM. CY helps detection of peritoneal micro-metastases but with low sensitivity. Radiomics is a novel and non-invasive image analysis method based on the mineable data from images. Benefiting from artificial intelligence (AI), radiomics can effectively improve diagnostic and prognostic accuracy of cancers, especially when integrated with clinical and molecular profile data. Thus, radiomics analysis of PM is a worthwhile research direction for preoperative assessment of GC.

In addition, Studies reported that certain tumors have the tendency of organotropic metastasis. Different cancer-derived PM seems to have specific abnormal gene expression, implicating the crucial role of genomics in PM diagnosis. Thus, potential biomarkers of fluid biopsies, such as ascites, need to be explored and verified effectively. Studies also showed that the composition of exosomes contains proteins, lipids, and nucleic acids; exosomal components as biomarkers of PM also need to be further explored.

This Research Topic welcomes Original Articles and Reviews encompassing basic and clinical studies on the peritoneal metastasis of gastric cancer, focusing on but not limited to the following topics:
(1) Potential diagnostic or prognostic biomarkers for PM of GC;
(2) Techniques for peritoneal micro-metastasis detection;
(3) Effective clinical, imaging, or molecular staging of PM;
(4) Mechanisms of “Seed-and-soil”;
(5) Research on tumor microenvironment or exosomes that reveal precise mechanisms of PM.

Keywords: Gastric Cancer, Peritoneal Metastasis, Biomarker, Therapy

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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