Wang Wangbiao, Li Yuxiang, Li Shiang, Lin Feng, Guo Jun, Liu Fuzhong, Abudusaimaiti Gulinaizaier, Liu Junyuan, Sun Gang
Oncology, Aksu Regional Chinese Medicine Hospital, Aksu, 843000, Xinjiang, China.
Xinjiang Cancer Center/Key Laboratory of Oncology of Xinjiang Uygur Autonomous Region, Urumqi, 830001, Xinjiang, China.
Sci Rep. 2025 May 30;15(1):19021. doi: 10.1038/s41598-025-99909-6.
GULP PTB domain containing engulfment adaptor 1 (GULP1) protein is involved in regulating biological processes such as endocytosis and apoptosis. The function of GULP1 in cancer, however, has been the subject of fewer studies; its importance as a potential prognostic factor in pancreatic cancer is still uncertain. Thus, the purpose of this work was to investigate GULP1's immunologic and oncogenic activities in a range of malignancies, as well as any potential relevance to pancreatic cancer. Using multiple bioinformatic databases, GULP1 expression, prognostic significance, mutation status, methylation and phosphorylation levels, biological functions, immune cell infiltration and immunotherapeutic responses and drug sensitivity were comprehensively assessed in pan-cancer and functionally validated in pancreatic cancer. The results revealed that GULP1 was differentially expressed in most tumours and correlated with poor prognostic indicators in most tumours, which may be related to the fact that GULP1 is involved in the regulation of apoptotic pathways. In addition, the differential expression of GULP1 was linked to immune cell infiltration levels, immunotherapy response, and chemotherapy resistance. GULP1 could hinder the body's ability to fight tumors and respond to immunotherapy by promoting the accumulation of immune cells and suppressing the activity of cytotoxic T lymphocytes. In pancreatic cancer, down-regulation of GULP1 expression inhibits proliferation, invasion and migration of pancreatic cancer cells. These phenotypic changes may be achieved by regulating HIPPO, mTOR, and RTK signaling pathways. Taken together, it makes sense to think that GULP1 could be a biomarker for immunotherapy and prognosis in pan- and pancreatic cancer.
含吞噬衔接蛋白1(GULP1)的GULP PTB结构域蛋白参与调节诸如内吞作用和细胞凋亡等生物学过程。然而,GULP1在癌症中的功能研究较少;其作为胰腺癌潜在预后因素的重要性仍不确定。因此,本研究旨在探讨GULP1在一系列恶性肿瘤中的免疫和致癌活性,以及与胰腺癌的潜在相关性。利用多个生物信息学数据库,对泛癌中的GULP1表达、预后意义、突变状态、甲基化和磷酸化水平、生物学功能、免疫细胞浸润、免疫治疗反应及药物敏感性进行了综合评估,并在胰腺癌中进行了功能验证。结果显示,GULP1在大多数肿瘤中差异表达,且与大多数肿瘤的不良预后指标相关,这可能与GULP1参与凋亡途径的调节有关。此外,GULP1的差异表达与免疫细胞浸润水平、免疫治疗反应及化疗耐药性有关。GULP1可通过促进免疫细胞积累和抑制细胞毒性T淋巴细胞活性来阻碍机体对抗肿瘤和免疫治疗的能力。在胰腺癌中,GULP1表达下调可抑制胰腺癌细胞的增殖、侵袭和迁移。这些表型变化可能通过调节HIPPO、mTOR和RTK信号通路来实现。综上所述,GULP1有望成为泛癌和胰腺癌免疫治疗及预后的生物标志物。