School of Life Sciences, 12657Northwest University, Xi'an, China.
Abmart, Shanghai, China.
Technol Cancer Res Treat. 2022 Jan-Dec;21:15330338221106855. doi: 10.1177/15330338221106855.
Lung cancer is a malignant tumor with the highest mortality rate in the world. It is necessary to develop effective biomarkers for diagnosis or prognostic treatment to improve the survival rate of patients. In this prospective study, we identified a membrane-expressed protein Tight Junction Protein 1 (TJP1), which is an ideal therapeutic target for lung cancer, and demonstrated its role in invasion, migration, and proliferation of lung cancer. High-throughput monoclonal antibody microarrays were used to screen for differential expression of monoclonal antibodies (mAbs) in lung cancer and normal lung tissue. Differentially expressed antibodies were used to immunoprecipitate their cellular targets to be identified by mass spectrometry. The identified target TJP1 was knocked down to observe the effect of reduced gene expression on lung cancer cell function. Immunohistochemistry on human tumor tissues and The Cancer Genome Atlas (TCGA) database was used to explore the relationship between TJP1 expression in multiple cancer types and patient prognosis. The antibody CL007473 was overexpressed in tumor tissue and its target protein was identified by mass spectrometry and immunofluorescence as TJP1, a membrane-expressed protein. Knockdown of TJP1 in lung cancer cell lines showed that reduced expression of TJP1 could inhibit the invasion and migration of lung cancer cells and inhibit the proliferation of cancer cells, suggesting that membrane-expressed protein TJP1 may be used as a therapeutic target for lung cancer. TCGA database analysis showed that TJP1 was highly expressed in pancreatic cancer (PAAD) tissues compared with normal tissues, and low expression was more beneficial to the prognosis and survival of PAAD patients. Membrane-expressed protein TJP1 may be a good therapeutic and prognostic target for lung cancer and has the potential to be a prognostic biomarker in pancreatic cancer.
肺癌是全球死亡率最高的恶性肿瘤。有必要开发有效的生物标志物用于诊断或预后治疗,以提高患者的生存率。在这项前瞻性研究中,我们鉴定了一种膜表达蛋白紧密连接蛋白 1(TJP1),它是肺癌的理想治疗靶点,并证明了它在肺癌侵袭、迁移和增殖中的作用。我们使用高通量单克隆抗体微阵列筛选肺癌和正常肺组织中差异表达的单克隆抗体(mAbs)。差异表达的抗体用于免疫沉淀其细胞靶标,并用质谱法鉴定。鉴定的靶标 TJP1 被敲低,以观察基因表达降低对肺癌细胞功能的影响。免疫组化检测人类肿瘤组织和癌症基因组图谱(TCGA)数据库,以探讨多种癌症类型中 TJP1 表达与患者预后的关系。抗体 CL007473 在肿瘤组织中过表达,其靶蛋白通过质谱和免疫荧光鉴定为 TJP1,一种膜表达蛋白。在肺癌细胞系中敲低 TJP1 表明,TJP1 表达降低可抑制肺癌细胞的侵袭和迁移,并抑制癌细胞的增殖,提示膜表达蛋白 TJP1 可能成为肺癌的治疗靶点。TCGA 数据库分析显示,与正常组织相比,TJP1 在胰腺癌(PAAD)组织中高表达,低表达更有利于 PAAD 患者的预后和生存。膜表达蛋白 TJP1 可能是肺癌的一个良好的治疗和预后靶点,并有可能成为胰腺癌的预后生物标志物。