TJP1, a Membrane-Expressed Protein, is a Potential Therapeutic and Prognostic Target for Lung Cancer.

Abstract

Objective: 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. Methods: 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. Results: 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. Conclusion: 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.