Abstract
Overexpression of the high mobility group protein A2 (HMGA2), an architectural transcription factor, has been linked to poor prognosis in many malignancies, although this remains controversial. Herein, we conducted a meta-analysis to investigate whether HMGA2 has prognostic value, and evaluated the association between HMGA2 and clinicopathologic factors in malignancies. A total of 29 studies involving 4114 patients were included in this meta-analysis. The pooled results demonstrated that elevated HMGA2 predicted a poor overall survival (OS) (hazard ratio [HR] = 1.82; 95% confidence interval [CI] = 1.62–2.05; P < 0.001) and disease-free survival/progression-free survival/recurrence-free survival (HR = 1.94; 95% CI = 1.27–2.98; P = 0.002). Subgroup analysis conducted by study region, sample size, detection method, and analysis method indicated that HMGA2 overexpression correlated with poor OS. Furthermore, HMGA2 overexpression was found to be linked to poor OS in various cancers except ovarian cancer (pooled HR = 1.14; 95% CI = 0.62–2.09; P = 0.673). High HMGA2 expression level also correlated with advanced TNM stage (OR = 2.44; 95% CI =1.87–3.2; P < 0.001), lymphovascular invasion (OR = 2.46, 95% CI = 1.67–3.64; P < 0.001), distant metastasis (OR = 2.66; 95% CI =1.51–4.69; P < 0.001), and lymph node metastasis (OR = 1.83; 95% CI =1.27–2.64; P = 0.001). In conclusion, HMGA2 overexpression indicates a worse prognosis and may serve as a prognostic predictor in cancer patients.
Highlights
Cancer is a major public health problem worldwide and the leading cause of death in China [1]
The expression of high mobility group protein A2 (HMGA2) was correlated with overall survival (OS) in 25 studies, and disease-free survival (DFS)/progression-free survival (PFS)/recurrence-free survival (RFS) in 4 studies
Several recent studies demonstrated that HMGA2 overexpression, both in the tissues and blood of patients with cancer correlated with poor tumor differentiation, positive lymph node metastasis, and advanced stage, indicating a poor prognosis [46, 47]
Summary
Cancer is a major public health problem worldwide and the leading cause of death in China [1]. High-mobility group AT-hook 2 (HMGA2), a member of the high mobility group (HMG) protein family, is a non-histone chromosomal protein [5, 6]. It modulates gene transcription by interacting with various transcription factors and altering the chromatin structure [6, 7], and is a known regulator of cell growth, differentiation, apoptosis, and DNA repair [8, 9]. Recent studies have revealed that the overexpression of HMGA2 correlates with higher lymph node metastasis rates, poor tumor differentiation, and unfavorable prognosis [10,11,12,13,14], implying that HMGA2 has prognostic value in cancer
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