晚期胃癌（GC）侵犯胃浆膜的预后往往不佳，主要由于腹膜复发的高发生率。腹膜转移的患者通常接受新辅助腹腔内和全身化疗（NIPS）。对NIPS的良好反应者通常进行手术治疗。本研究旨在探讨预测腹膜转移（PM）发生的生物标志物，并评估NIPS在GC患者中的疗效。我们通过腹腔内接入口收集了两名患有PM、两名未患PM以及两名经NIPS后PM减轻的患者的六个腹膜灌洗（PL）样本。我们从PL样本的外泌体中等量分离了微RNA（miRNA）用于深度测序。筛选出两个miRNA（hsa-let-7g-3p和hsa-miR-10395-3p），并利用qRT-PCR检查了99名GC患者PL样本中它们的表达水平。此外，我们进行了体内外功能实验，以研究这些miRNA对GC细胞转移和化疗抗性的影响。PL样本的六个外泌体miRNA表达谱表明，减轻PM患者的PL外泌体中的miRNA签名类似于未患PM患者的PL。hsa-let-7g-3p和hsa-miR-10395-3p的表达水平与PM相关。体内外功能实验确认，hsa-let-7g-3p和hsa-miR-10395-3p参与了GC转移和化疗抗性。GC PL中的外泌体含有与PM相关的大量miRNA。此外，hsa-let-7g-3p和hsa-miR-10395-3p可以用作预测PM和NIPS疗效的生物标志物，参与了GC的转移和化疗抗性。© 2023年。本文作者在国际胃癌协会和日本胃癌协会独家许可下发表。

The prognosis of advanced gastric cancer (GC) invading the gastric serosa remains poor, mainly owing to high incidence of peritoneal recurrence. Patients with peritoneal metastases are often treated with neoadjuvant intraperitoneal and systemic chemotherapies (NIPS). Good responders to NIPS often undergo conversion gastrectomy. This study aims to explore biomarkers predicting the occurrence of peritoneal metastasis (PM) and evaluating the efficacy of NIPS in GC patients.We collected six peritoneal lavage (PL) samples from two patients with PM, two without PM, and two with diminished PM after NIPS via intraperitoneal access ports. We equally isolated microRNAs from exosomes derived from PL samples for deep sequencing. Two microRNAs (hsa-let-7g-3p and hsa-miR-10395-3p) were identified, and their expression levels were examined in PL samples of 99 GC patients using qRT-PCR. Moreover, we performed in vivo and in vitro functional assays to investigate effects of these microRNAs on metastasis and chemoresistance of GC cells.Exosomal microRNA expression profiling of six PL samples indicated that the microRNA signature in exosomes of PLs from patients with diminished PM was similar to that from patients without PM. Expression levels of hsa-let-7g-3p and hsa-miR-10395-3p were associated with PM. In vivo and in vitro functional assays confirmed that hsa-let-7g-3p and hsa-miR-10395-3p are involved in GC metastasis and chemoresistance.PL-derived exosomes in GC contain large amounts of microRNAs related to PM. Moreover, hsa-let-7g-3p and hsa-miR-10395-3p could be used as biomarkers predicting PM and NIPS efficacy and are involved in GC metastasis and chemoresistance.© 2023. The Author(s) under exclusive licence to The International Gastric Cancer Association and The Japanese Gastric Cancer Association.