Overexpression of High Mobility Group A1 Protein in Human Uveal Melanomas: Implication for Prognosis

<div><p>There is increasing evidence that the high mobility group A1 (HMGA1) protein, which functions as a transcriptional master regulator, plays critical roles in tumor progression. We evaluated HMGA1 expression in 89 primary uveal melanomas (UM) by immunohistochemistry to determine the clinicopathological and prognostic value of HMGA1 in UM after adjusting for other prognostic variables. Nuclear expression of HMGA1 was detected in 44% UMs. High expression levels of HMGA1 were more frequent in UMs with high levels of epithelioid cell pattern, mitoses count, and Ki67 labeling index (<i>P</i> = 0.025, <i>P</i><0.0001, <i>P</i> = 0.0018; respectively), and HMGA1 expression levels were directly correlated with Ki67 labeling indexes and mitoses counts (R = 0.31, <i>P</i> <0.0001; R = 0.27, <i>P</i><0.0068; respectively). High expression of HMGA1 was also independently associated with an increased risk of distant metastases as determined using the Cox proportional hazards regression model (multivariate hazard ratio: 3.44; 95% confidence interval: 1.56–7.60; log rank <i>P</i> = 0.0022). Moreover, high HMGA1 expression was associated with shorter UM-specific survival (multivariate hazard ratio: 2.41; 95% confidence interval: 1.10–5.53; log rank P = 0.041). These findings suggest that high levels of HMGA1 are associated with adverse clinical outcomes in UM patients and that further evaluation of HMGA1 as a potential therapeutic target in UM is warranted.</p></div

Expression of HMGA1 in UM.

<p>Detection of high mobility group A 1 (HMGA1) immunoreactivity in UM. <b>A</b>, HMGA1 expression in melanoma spindle cells (Scale bar – 100µm). <b>B</b>, HMGA1 expression in melanoma epithelioid cells (Scale bar – 50µm).</p

Clinical, pathologic characteristics according to HMGA1 alterations in uveal melanoma.

<p>Clinical, pathologic characteristics according to HMGA1 alterations in uveal melanoma.</p

Kaplan-Meier curves for survival in UM patients.

<p>Survival of UM patients were estimated according to HMGA1 expression levels and Ki67 LI. Significant differences in disease-free survival rates were observed (<b>A, B</b>). Significant differences in disease-specific survival rates were also observed (<b>C, D</b>). P values were calculated with a log-rank test.</p

Clinicopathological features, tumor markers, HMGA1, and uveal melanoma patients' survival.

<p>Abbreviations: HR, hazard ratio; CI, confidence interval.</p>1<p>The multivariate Cox regression model initially included the HMGA1 expression variable (high or low), age of diagnosis, sex, largest basal tumor diameter, tumor thickness and epithelioid cell pattern.</p

Additional file 2 of MRI-assessed diaphragmatic function can predict frequent acute exacerbation of COPD: a prospective observational study based on telehealth-based monitoring system

Additional file 2. Correlation between diaphragm function and clinical parameters in the COPD grou