6 research outputs found

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

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    <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.

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    <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

    Kaplan-Meier curves for survival in UM patients.

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    <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.

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    <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

    Multimolecular characteristics of cell-death related hub genes in human cancers: a comprehensive pan-cancer analysis

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    Failure of the normal process of cell death pathways contributes to the defection of immune systems and the occurrence of cancers. The key genes, the multimolecular mechanisms, and the immune functions of these genes in pan-cancers remain unclear. Using online databases of The Cancer Genome Atlas, GEPIA2, TISIDB, HPA, Kaplan-Meier Plotter, PrognoScan, cBioPortal, GSCALite, TIMER, and Sangerbox, we identified the key genes from the six primary cell death-related pathways and performed a comprehensive analysis to investigate the multimolecular characteristics and immunological functions of the hub genes in 33 human cancers. We identified five hub genes in the six primary cell death-related pathways (JUN, NFKB1, CASP3, PARP1, and TP53). We found that CASP3, PARP1, and TP53 were overexpressed in 28, 23, and 27 cancers. The expression of the five genes was associated with the development and prognosis of many cancers. Particularly, JUN, NFKB1, CASP3, and TP53 have prognostic values in Brain Lower Grade Glioma (LGG), while PARP1 and CASP3 could predict the survival outcomes in Adrenocortical carcinoma (ACC). In addition, an extensive association between five genes’ expression, DNA methylation, and tumor-immune system interactions was noticed. The five cell death-related hub genes could function as potential biomarkers for various cancers, particularly LGG and ACC. The immunological function analysis of the five genes also proposes new targets for developing immunosuppressants and improving the immunotherapy efficacy of cancers. However, further extensive clinical and experimental research are required to validate their clinical values.</p
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