腹膜转移是进展期胃癌根治手术失败的主要原因，申请者在前期研究中发现早期胃癌腹膜转移患者腹腔中同时存在“成团型”及孤立脱落癌细胞，通过肿瘤球及克隆形成实验证实“成团型”脱落癌细胞具有很强的干细胞特性；在配对基因检测中我们发现了在“成团型”脱落癌细胞中TXNIP基因表达显著上调，TXNIP可以通过诱导线粒体DNA损伤，启动细胞自噬。基于此我们提出高表达TXNIP的细胞团通过自噬维持细胞团内部养分供给，抵制失巢性死亡并维持其干细胞特性。同时，自噬的“成团型”脱落癌细胞亦可抵御全身化疗和腹腔灌注化疗的细胞毒性损伤进而造成腹膜转移。本研究以TXNIP调控“成团型”脱落癌细胞的形成及自噬发生，自噬对“成团型”脱落癌细胞干细胞特性及转移潜能的维持为核心研究内容，以新的视角解释胃癌腹膜转移的成因。

Peritoneal metastasis is the major reason for the failure of radical surgery in advanced gastric cancer. In this study, we have shown clustered and isolated tumor exfoliated cells existed in abdominal cavities of early-stage gastric cancer patients simultaneously, and we confirmed that clustered tumor exfoliated cells have strong stemness characters of stem cell by tumorsphere formation and .clonogenic assay. In gene chip paired analysis, we discovered that TXNIP expression significantly increased in clustered tumor exfoliated cells, TXNIP can activate cell autophagy through inducing DNA damage of mitochondrial. Based on the above content, we propose that clustered tumor cells with high-expressed TXNIP maintain interior nutrient supply by cell autophagy, resisted cell anoikis and retained the stemness characters of stem cell. At the same time, clustered tumor cells with cell autophagy inside could resist the peritoneal metastasis caused by the cytotoxic damage of systemic chemotherapy and hyperthermic intraoperative intraperitoneal chemotherapy. This study will focus on the clustered tumor cell formation and autophagy regulated by TXNIP, the role of autophagy in maintaining the stem cell characters of clustered tumor cells and potential of metastasis will be highly concerned. A total fresh perspective will be offered to explain the reason of gastric cancer peritoneal metastasis.