High expression of tight junction protein 1 as a predictive biomarker for bladder cancer grade and staging

Yi-Chen Lee,Wei-Ting Kuo,Kuo-Wang Tsai,Yi-Fang Yang,Jia-Bin Liao,Yu-Chan Chang

doi:10.1038/s41598-022-05631-y

Abstract

Tight junction proteins 1–3 (TJP1–3) are components of tight junctions that can link transmembrane proteins to the actin cytoskeleton, and their incidence directly correlates to metastasis. However, the role of the TJP family in bladder cancer has not been adequately evaluated. In this study, we evaluated the genetic changes, mRNA and protein expressions of the target genes of the TJP family in bladder cancer patients using online database and immunohistochemistry, respectively. We found that TJP1 was amplified in bladder cancer tissue and that the protein expression levels were significantly associated with age (p = 0.03), grade (p = 0.007), and stage (p = 0.011). We also examined the correlation between TJP1 and other high-frequency mutation genes using TIMER. TJP1 mRNA levels were positively correlated with TTN and RYR3 mRNA levels in bladder cancer tissue. Taken together, TJP1 expression is associated with poor clinical outcomes in patients with bladder cancer and can be a useful predictive biomarker for bladder cancer staging.

Highlights

Tight junction proteins 1–3 (TJP1–3) are components of tight junctions that can link transmembrane proteins to the actin cytoskeleton, and their incidence directly correlates to metastasis
By evaluating the mRNA expression of TJP1, TJP2, and TJP3 in 40 different cancer cell lines, we found that TJP1, TJP2, and TJP3 were upregulated in 29, 40, and 12 different cancer cell types, respectively (Fig. 1)
While analyzing the frequency of the co-occurrence of genetically altered TJP1–3 in the same specimen, it was found that genetic alterations of the other TJP family members were not significant in bladder cancer patients (Supplementary Table 1)

Summary

Introduction

Tight junction proteins 1–3 (TJP1–3) are components of tight junctions that can link transmembrane proteins to the actin cytoskeleton, and their incidence directly correlates to metastasis. We evaluated the genetic changes, mRNA and protein expressions of the target genes of the TJP family in bladder cancer patients using online database and immunohistochemistry, respectively. When the MIBC progresses into metastatic bladder cancer, the 5-year survival rate of patients is significantly r educed[4]. ZO proteins play an important role in the formation of tight junctions that directly interact with the PDZ domain (ZO-1 or ZO-2) and the C-terminus of c laudins[13]. These proteins modulate several signaling pathways in cancer cells. Based on the analysis of the bioinformation, we identified the target genes and provided the clinicopathological data for verification relationships in patients with bladder cancer

Methods

Results

Conclusion