The HMGA2 protein plasma levels and their association with tumor size in Syrian patients with bladder cancer

Background: Bladder cancer is an occupational cancer caused primarily by exposure to tobacco combustion products. The primarily aim in managing bladder cancer is to prevent progression and reduce recurrence. Therefore, it was vital to search for a biomarker that would support the approach to diagnose bladder cancer and that would be non-invasive, painless, and increase the patient's compliance with the diagnosing approach. The HMGA2 protein belongs to the HMG proteins family, and it is an oncofetal protein that participates in various stages of carcinogenesis and cancer development, which made it the focus of attention of many studies investigating HMGA2 protein expression and its levels in different types of cancer. The aim of this study is to investigate the presence and levels of the HMGA2 protein in the plasma of bladder cancer patients with different overall stages and healthy individuals and the correlation of its levels with tumor size (focal or huge tumor).

Materials and methods: This study included 74 Syrian individuals who were divided into two groups: an apparently healthy individuals group (n=22) and a group of newly diagnosed bladder cancer patients who will undergo tumor resection after drawing a blood sample and have not started any treatment and have no history of other cancers (n=52). There were 27 patients with focal tumors and 25 patients with huge tumors. The HMGA2 plasma concentrations were measured by enzyme-linked immunosorbent assay (ELISA). Statistical analysis was performed using SPSS version 25 (SPSS Inc., Chicago, IL, USA), and the values were compared between each two groups using t-test, while correlations were studied using Pearson and Spearman tests. P-value < 0.05 was considered as a statistically significant value.

Results: Plasma HMGA2 protein levels were higher in the bladder cancer (BC) group than in the healthy group (P-value < 0.0001).plasma HMGA2 levels were higher in patients with huge tumors compared to patients with focal tumors (P-value = 0.001). Increased plasma HMGA2 protein levels were associated with increased tumor size (P-value = 0.004). plasma HMGA2 levels were higher in patients with stage (II + III) compared to patients with stage (0 + I).

Conclusions: The present study confirmed the increase in HMAGA2 plasma levels in patients with bladder cancer compared to healthy individuals, and the increase in its plasma levels was associated with increased tumor size, as it was higher in bladder cancer patients with huge tumors than in bladder cancer patients with focal tumors. Similarly, the HMGA2 plasma levels in patients with stage (II + III) were higher than in patients with stage (0 + I). Therefore, plasma HMGA2 protein levels represent a potential biomarker that could be included in the bladder cancer diagnosis approach, which increases in patients with advanced stages, and the tumor size can be inferred from it.

Keywords: Bladder cancer – HMGA2 – Plasma – Focal tumor – Large tumor – Overall stage.