PPT1在胃癌中的预后价值及其对癌细胞脂质代谢的作用和机制
- 2026-11-07 18:22:49
KLF10通过下调NF-κB/NLRP3通路改善大鼠焦虑性抑郁行为及神经炎症KLF10
黄炳轶1,2,3, 高玉洁1,2,3, 谢靖宜1,2,3, 严晨2,3, 顾梦茹2,3, 张志郅2,3, 郭锦涛1,2,3, 刘嵩1,2,3, 王子良1,2,3, 杨玉萍4, 左芦根1,2, 陈德利1,2
1.
2.
3.
4.
摘要
目的探讨棕榈酰蛋白硫酯酶1（PPT1）在胃癌组织中的表达规律及其与患者临床预后的关系，并阐明其调控癌细胞脂质代谢的分子机制。
方法 联合TCGA-STAD数据库与临床样本免疫组化染色，分析PPT1在胃癌组织及癌旁组织中的表达差异。回顾性纳入136例接受根治性切除的胃癌患者，提取其病理与随访参数，运用Kaplan-Meier法、单因素及多因素Cox回归模型分析PPT1表达与术后5年生存率的关联，据此建立生存预测列线图并使用ROC曲线评估其效能。此外，结合GO及REACTOME数据库进行生物学通路富集。体外水平上，通过慢病毒转染构建胃癌细胞系模型，利用CCK-8法及Transwell小室法分别检测细胞增殖、迁移和侵袭能力。采用油红O染色、Western blotting实验以及抑制剂U0126逆转实验，探讨PPT1介导ERK信号通路对脂质代谢的调控作用。
结果 PPT1蛋白定位于细胞质，其在胃癌组织中的表达水平显著高于癌旁正常组织。PPT1高表达与患者外周血CEA、CA19-9水平的上升以及较高的T、N分期密切相关（P<0.05）。生存分析及Cox回归提示，PPT1高表达是导致患者术后5年生存率下降的独立危险因素。基于该指标构建的列线图显示出良好的预测准确度（C-index=0.812），其对应的ROC曲线AUC值为0.837。体外实验证实，下调PPT1表达可显著抑制胃癌细胞的增殖及侵袭转移能力，而过表达PPT1则起到反向的促进作用（P<0.05）。机制方面，过表达PPT1不仅诱导了细胞内脂质的异常蓄积，还显著上调了SREBP-1及FASN等脂质合成关键蛋白的表达（P<0.05）。该促脂质生成效应及其伴随的ERK通路激活，均可被U0126有效逆转。
结论胃癌组织中PPT1呈显著的高表达状态且提示患者预后不良。PPT1可能通过激活ERK信号通路影响胃癌细胞脂质代谢，从而助推肿瘤的恶性进展。PPT1有望作为胃癌的新型预后生物标志物与潜在干预靶点。
关键词：
↓更多详情请点击最下方“阅读原文”查看全文↓
Prognostic value of palmitoyl-protein thioesterase-1 in gastric cancer and its regulatory role in tumor cell lipid metabolism
HUANG Bingyi1,2,3, GAO Yujie1,2,3, XIE Jingyi1,2,3, YAN Chen2,3, GU Mengru2,3, ZHANG Zhizhi2,3, GUO Jintao1,2,3, LIU Song1,2,3, WANG Ziliang1,2,3, YANG Yuping4, ZUO Lugen1,2, CHEN Deli1,2
1.
2.
3.
4.
Abstract
Objective To investigate palmitoyl-protein thioesterase-1 (PPT1) expression in gastric cancer (GC), its prognostic significance, and its regulatory role in tumor cell lipid metabolism.
MethodsPPT1 expression was analyzed using TCGA-STAD data and immunohistochemistry of clinical samples. In a retrospective cohort of 136 GC patients undergoing radical resection, the association between PPT1 and 5-year survival was evaluated using Kaplan-Meier and Cox regression analyses, and a nomogram was constructed and validated by ROC analysis. GO and REACTOME enrichment analyses were conducted to identify the pathways involved. In cultured GC cell lines with PPT1 knockdown or overexpression, the changes in cell proliferation, migration and invasion were assessed using CCK-8 and Transwell assays. Oil Red O staining, Western blotting and U0126 rescue experiments were performed to explore the role of PPT1-mediated ERK signaling in tumor cell lipid metabolism.
Results PPT1 protein, localized in the cytoplasm, was significantly upregulated in GC tissues compared with adjacent normal tissues. High PPT1 expression was closely correlated with elevated serum CEA and CA19-9 levels and advanced T and N stages (P<0.05), and was an independent risk factor for reduced 5-year postoperative survival. The nomogram incorporating PPT1 showed good predictive accuracy (C-index=0.812) with an AUC of 0.837. In cultured GC cells, PPT1 knockdown significantly suppressed while PPT1 overexpression promoted cell proliferation, migration and invasion. PPT1 overexpression induced abnormal intracellular lipid accumulation in GC cells and significantly upregulated the expressions of the key lipogenic proteins SREBP 1 and FASN, and this pro-lipogenic effect and subsequent ERK signaling activation were effectively reversed by U0126.
Conclusion PPT1 is overexpressed in GC tissues and predicts poor prognosis. PPT1 overexpression promotes GC progression by activating the ERK signaling pathway and thereby modulating lipid metabolism, suggesting its potential as a novel prognostic biomarker and a therapeutic target for GC.
Keywords：
↓更多详情请点击最下方“阅读原文”查看全文↓
本文引用格式
黄炳轶, 高玉洁, 谢靖宜, 严晨, 顾梦茹, 张志郅, 郭锦涛, 刘嵩, 王子良, 杨玉萍, 左芦根, 陈德利.
HUANG Bingyi, GAO Yujie, XIE Jingyi, YAN Chen, GU Mengru, ZHANG Zhizhi, GUO Jintao, LIU Song, WANG Ziliang, YANG Yuping, ZUO Lugen, CHEN Deli.
CN 44-1627/R
ISSN 2097-4868 (网络)
ISSN 1673-4254 (印刷)
编辑：李 昊
初审：郎 朗
复审：林 萍
终审：孙昌朋
