PDF(Pubmed)
Abstract：
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is renowned for its formidable and lethal nature, earning it a notorious reputation among malignant tumors. Due to its challenging early diagnosis, high malignancy, and resistance to chemotherapy drugs, the treatment of pancreatic cancer has long been exceedingly difficult in the realm of oncology. γ-Glutamyl cyclotransferase (GGCT), a vital enzyme in glutathione metabolism, has been implicated in the proliferation and progression of several tumor types, while the biological function of GGCT in pancreatic ductal adenocarcinoma remains unknown.
METHODS: The expression profile of GGCT was validated through western blotting, immunohistochemistry, and RT-qPCR in both pancreatic cancer tissue samples and cell lines. Functional enrichment analyses including GSVA, ssGSEA, GO, and KEGG were conducted to explore the biological role of GGCT. Additionally, CCK8, Edu, colony formation, migration, and invasion assays were employed to evaluate the impact of GGCT on the proliferation and migration abilities of pancreatic cancer cells. Furthermore, the LASSO machine learning algorithm was utilized to develop a prognostic model associated with GGCT.
RESULTS: Our study revealed heightened expression of GGCT in pancreatic cancer tissues and cells, suggesting an association with poorer patient prognosis. Additionally, we explored the immunomodulatory effects of GGCT in both pan-cancer and pancreatic cancer contexts, found that GGCT may be associated with immunosuppressive regulation in various types of tumors. Specifically, in patients with high expression of GGCT in pancreatic cancer, there is a reduction in the infiltration of various immune cells, leading to poorer responsiveness to immunotherapy and worse survival rates. In vivo and in vitro assays indicate that downregulation of GGCT markedly suppresses the proliferation and metastasis of pancreatic cancer cells. Moreover, this inhibitory effect appears to be linked to the regulation of GGCT on c-Myc. A prognostic model was constructed based on genes derived from GGCT, demonstrating robust predictive ability for favorable survival prognosis and response to immunotherapy.
METHODS: The expression profile of GGCT was validated through western blotting, immunohistochemistry, and RT-qPCR in both pancreatic cancer tissue samples and cell lines. Functional enrichment analyses including GSVA, ssGSEA, GO, and KEGG were conducted to explore the biological role of GGCT. Additionally, CCK8, Edu, colony formation, migration, and invasion assays were employed to evaluate the impact of GGCT on the proliferation and migration abilities of pancreatic cancer cells. Furthermore, the LASSO machine learning algorithm was utilized to develop a prognostic model associated with GGCT.
RESULTS: Our study revealed heightened expression of GGCT in pancreatic cancer tissues and cells, suggesting an association with poorer patient prognosis. Additionally, we explored the immunomodulatory effects of GGCT in both pan-cancer and pancreatic cancer contexts, found that GGCT may be associated with immunosuppressive regulation in various types of tumors. Specifically, in patients with high expression of GGCT in pancreatic cancer, there is a reduction in the infiltration of various immune cells, leading to poorer responsiveness to immunotherapy and worse survival rates. In vivo and in vitro assays indicate that downregulation of GGCT markedly suppresses the proliferation and metastasis of pancreatic cancer cells. Moreover, this inhibitory effect appears to be linked to the regulation of GGCT on c-Myc. A prognostic model was constructed based on genes derived from GGCT, demonstrating robust predictive ability for favorable survival prognosis and response to immunotherapy.
摘要：
背景：胰腺导管腺癌（PDAC）以其强大而致命的性质而闻名，在恶性肿瘤中声名狼藉.由于其具有挑战性的早期诊断，恶性程度高,以及对化疗药物的耐药性，在肿瘤学领域，胰腺癌的治疗一直非常困难。γ-谷氨酰环基转移酶（GGCT），谷胱甘肽代谢中的一种重要酶，与几种肿瘤类型的增殖和进展有关，而GGCT在胰腺导管腺癌中的生物学功能尚不清楚。
方法：通过蛋白质印迹验证GGCT的表达谱，免疫组织化学，和RT-qPCR在胰腺癌组织样品和细胞系。功能富集分析，包括GSVA，ssGSEA,GO,和KEGG进行了研究，以探讨GGCT的生物学作用。此外,CCK8,Edu,菌落形成,迁移,并采用侵袭试验评价GGCT对胰腺癌细胞增殖和迁移能力的影响。此外，利用LASSO机器学习算法建立与GGCT相关的预后模型.
结果：我们的研究表明，GGCT在胰腺癌组织和细胞中的表达增加，提示与患者预后较差有关。此外,我们探索了GGCT在泛癌症和胰腺癌环境中的免疫调节作用，发现GGCT在各种类型的肿瘤中可能与免疫抑制调节有关。具体来说,在胰腺癌中GGCT高表达的患者中，各种免疫细胞的浸润减少，导致对免疫疗法的反应性较差，生存率较差。体内和体外实验表明，GGCT的下调可显着抑制胰腺癌细胞的增殖和转移。此外，这种抑制作用似乎与GGCT对c-Myc的调节有关。基于来自GGCT的基因构建了一个预后模型，证明了良好的生存预后和免疫疗法反应的强大预测能力。
方法：通过蛋白质印迹验证GGCT的表达谱，免疫组织化学，和RT-qPCR在胰腺癌组织样品和细胞系。功能富集分析，包括GSVA，ssGSEA,GO,和KEGG进行了研究，以探讨GGCT的生物学作用。此外,CCK8,Edu,菌落形成,迁移,并采用侵袭试验评价GGCT对胰腺癌细胞增殖和迁移能力的影响。此外，利用LASSO机器学习算法建立与GGCT相关的预后模型.
结果：我们的研究表明，GGCT在胰腺癌组织和细胞中的表达增加，提示与患者预后较差有关。此外,我们探索了GGCT在泛癌症和胰腺癌环境中的免疫调节作用，发现GGCT在各种类型的肿瘤中可能与免疫抑制调节有关。具体来说,在胰腺癌中GGCT高表达的患者中，各种免疫细胞的浸润减少，导致对免疫疗法的反应性较差，生存率较差。体内和体外实验表明，GGCT的下调可显着抑制胰腺癌细胞的增殖和转移。此外，这种抑制作用似乎与GGCT对c-Myc的调节有关。基于来自GGCT的基因构建了一个预后模型，证明了良好的生存预后和免疫疗法反应的强大预测能力。
