The Affiliated Lihuili Hospital, Ningbo University, Ningbo, Zhejiang 315040, China.
Ningbo Clinical Pathology Diagnosis Center, Ningbo, Zhejiang 315211, China.
Aging (Albany NY). 2023 Aug 16;15(16):8013-8025. doi: 10.18632/aging.204941.
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignant disease with low overall survival; chemotherapy and immunotherapy have limited efficacy. Tumor necrosis factor receptor 2 (TNFR2), a type II transmembrane protein, contributes to the development and progression of several tumors. In this study, we elucidated the effect and molecular mechanisms of TNFR2.
We used The Cancer Genome Atlas and the Genotype-Tissue Expression database to compare the expression of the TNFR2 gene between normal and malignant pancreatic tissue. Using immunohistochemical staining, we divided the patients into high and low-expression groups, then investigated clinicopathologic data and survival curves of pancreatic cancer patients. We measured TNFR2 protein expression in PANC-1 and ASPC-1 pancreatic cancer cells subjected to TNFR2 small interfering RNA or negative control treatment. We performed proliferation, invasion, and migration assays to study the biological effects of TNFR2 in PDAC. The molecular mechanisms were validated using western blotting.
TNFR2 was more highly expressed in PDAC cells and tissues than controls. Abundant expression of TNFR2 was associated with aggressive clinicopathologic characteristics and poor outcomes. Overexpression of TNFR2 promoted PDAC cell proliferation, migration, and invasion . Mechanistically, TNFR2 binds to TNF-α and activates the NF-κB signaling pathway.
TNFR2 is a prognostic marker that facilitates the proliferation, migration, and invasion of PDAC via the NF-κB signaling pathway. TNFR2 may become a therapeutic target.
胰腺导管腺癌（PDAC）是一种侵袭性很强的恶性疾病，总体存活率低；化疗和免疫疗法的疗效有限。肿瘤坏死因子受体 2（TNFR2）是一种 II 型跨膜蛋白，有助于几种肿瘤的发生和发展。在这项研究中，我们阐明了 TNFR2 的作用和分子机制。
我们使用癌症基因组图谱和基因型组织表达数据库比较了正常和恶性胰腺组织中 TNFR2 基因的表达。通过免疫组织化学染色，我们将患者分为高表达组和低表达组，然后调查了胰腺癌患者的临床病理数据和生存曲线。我们测量了 TNFR2 小干扰 RNA 或阴性对照处理后的 PANC-1 和 ASPC-1 胰腺癌细胞中 TNFR2 蛋白的表达。我们进行了增殖、侵袭和迁移实验，以研究 TNFR2 在 PDAC 中的生物学效应。通过 Western blot 验证了分子机制。
TNFR2 在 PDAC 细胞和组织中的表达高于对照组。TNFR2 的大量表达与侵袭性临床病理特征和不良预后相关。TNFR2 的过表达促进了 PDAC 细胞的增殖、迁移和侵袭。机制上，TNFR2 与 TNF-α结合并激活 NF-κB 信号通路。
TNFR2 是一种预后标志物，通过 NF-κB 信号通路促进 PDAC 的增殖、迁移和侵袭。TNFR2 可能成为一种治疗靶点。
