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Abstract：
OBJECTIVE: Pancreatic cancer is a lethal malignancy with a grim prognosis. Previous studies have proven that Leucine Rich Repeat of Flightless-1 Interacting Protein 1 (LRRFIP1) plays a pivotal role in cell biological processes, while its clinical significance and function in pancreatic cancer remain to be elucidated. Hence, we aimed to explore the roles and mechanisms of LRRFIP1 in pancreatic cancer.
METHODS: The expression of LRRFIP1 in pancreatic cancer tissues and its clinical significance for pancreatic cancer were analyzed by immunohistochemistry assay and bioinformatic analysis. The influences of LRRFIP1 on the proliferation and migration of pancreatic cancer cells were assessed in vitro. The underlying mechanisms of LRRFIP1 in pancreatic cancer progression were explored using gene set enrichment analysis (GSEA) and molecular experiments.
RESULTS: The results showed that LRRFIP1 expression was significantly upregulated in pancreatic cancer tissues compared to the normal tissues, and such upregulation was associated with poor prognosis of patients with pancreatic cancer. GSEA revealed that LRRFIP1 upregulation was significantly associated with various cancer-associated signaling pathways, including PI3K/AKT signaling pathway and Wnt pathway. Furthermore, LRRFIP1 was found to be associated with the infiltration of various immune cells. Functionally, LRRFIP1 silencing suppressed cell proliferation somewhat and inhibited migration substantially. Further molecular experiments indicated that LRRFIP1 silencing inactivated the AKT/GSK-3β/β-catenin signaling axis.
CONCLUSIONS: Taken together, LRRFIP1 is associated with tumorigenesis, immune cell infiltration, and prognosis in pancreatic cancer, which suggests that LRRFIP1 may be a potential biomarker and therapeutic target for pancreatic cancer.
METHODS: The expression of LRRFIP1 in pancreatic cancer tissues and its clinical significance for pancreatic cancer were analyzed by immunohistochemistry assay and bioinformatic analysis. The influences of LRRFIP1 on the proliferation and migration of pancreatic cancer cells were assessed in vitro. The underlying mechanisms of LRRFIP1 in pancreatic cancer progression were explored using gene set enrichment analysis (GSEA) and molecular experiments.
RESULTS: The results showed that LRRFIP1 expression was significantly upregulated in pancreatic cancer tissues compared to the normal tissues, and such upregulation was associated with poor prognosis of patients with pancreatic cancer. GSEA revealed that LRRFIP1 upregulation was significantly associated with various cancer-associated signaling pathways, including PI3K/AKT signaling pathway and Wnt pathway. Furthermore, LRRFIP1 was found to be associated with the infiltration of various immune cells. Functionally, LRRFIP1 silencing suppressed cell proliferation somewhat and inhibited migration substantially. Further molecular experiments indicated that LRRFIP1 silencing inactivated the AKT/GSK-3β/β-catenin signaling axis.
CONCLUSIONS: Taken together, LRRFIP1 is associated with tumorigenesis, immune cell infiltration, and prognosis in pancreatic cancer, which suggests that LRRFIP1 may be a potential biomarker and therapeutic target for pancreatic cancer.
摘要：
目的：胰腺癌是一种致命的恶性肿瘤，预后不良。先前的研究已经证明，Flightless-1相互作用蛋白1（LRRFIP1）在细胞生物学过程中起着关键作用，而其在胰腺癌中的临床意义和功能仍有待阐明。因此，我们旨在探讨LRRFIP1在胰腺癌中的作用和机制。
方法：采用免疫组织化学和生物信息学方法分析LRRFIP1在胰腺癌组织中的表达及其临床意义。在体外评估了LRRFIP1对胰腺癌细胞增殖和迁移的影响。使用基因集富集分析（GSEA）和分子实验探索了LRRFIP1在胰腺癌进展中的潜在机制。
结果：结果显示，与正常组织相比，LRRFIP1在胰腺癌组织中的表达明显上调，这种上调与胰腺癌患者的不良预后相关。GSEA显示LRRFIP1上调与各种癌症相关的信号通路显著相关。包括PI3K/AKT信号通路和Wnt通路。此外，发现LRRFIP1与各种免疫细胞的浸润有关。功能上,LRRFIP1沉默在一定程度上抑制了细胞增殖，并基本抑制了迁移。进一步的分子实验表明LRRFIP1沉默使AKT/GSK-3β/β-连环蛋白信号轴失活。
结论：综合来看，LRRFIP1与肿瘤发生有关，免疫细胞浸润，和胰腺癌的预后，这表明LRRFIP1可能是胰腺癌的潜在生物标志物和治疗靶点。
方法：采用免疫组织化学和生物信息学方法分析LRRFIP1在胰腺癌组织中的表达及其临床意义。在体外评估了LRRFIP1对胰腺癌细胞增殖和迁移的影响。使用基因集富集分析（GSEA）和分子实验探索了LRRFIP1在胰腺癌进展中的潜在机制。
结果：结果显示，与正常组织相比，LRRFIP1在胰腺癌组织中的表达明显上调，这种上调与胰腺癌患者的不良预后相关。GSEA显示LRRFIP1上调与各种癌症相关的信号通路显著相关。包括PI3K/AKT信号通路和Wnt通路。此外，发现LRRFIP1与各种免疫细胞的浸润有关。功能上,LRRFIP1沉默在一定程度上抑制了细胞增殖，并基本抑制了迁移。进一步的分子实验表明LRRFIP1沉默使AKT/GSK-3β/β-连环蛋白信号轴失活。
结论：综合来看，LRRFIP1与肿瘤发生有关，免疫细胞浸润，和胰腺癌的预后，这表明LRRFIP1可能是胰腺癌的潜在生物标志物和治疗靶点。
