Prognostic Value of HMGA2 in Human Cancers: A Meta-Analysis Based on Literatures and TCGA Datasets

Abstract

Background: Emerging evidences have shown that the high-mobility group protein A2 (HMGA2) can aberrantly express in human cancers, and it could be an unfavorable prognostic factor in cancer patients. However, the prognostic value of HMGA2 was still unclear. Therefore, in this study, we explored the potential prognostic value of HMGA2 in human cancers by using meta-analysis based on published literatures and The Cancer Genome Atlas (TCGA) datasets.Methods: Through searching PubMed, Embase, Web of Science and Cochrane Library databases, we were able to identify the studies evaluating the prognostic value of HMGA2 in cancers. Then, UALCAN and TCGA datasets were used to validate the results of our meta-analysis.Results: In all, 15 types of cancers were included in this meta-analysis. Pooled results showed that high level of HMGA2 was significantly correlated with poor OS (HR = 1.88, 95% confidence interval (CI) = 1.68-2.11, P < 0.001) and poor DFS (HR = 2.49, 95% CI = 1.44-4.28, P = 0.001) in cancer patients. However, subgroup analyses revealed that the high expressed HMGA2 was associated with poor OS in head and neck cancer, gastric cancer and colorectal cancer, but not esophageal cancer and ovarian cancer. Based on TCGA datasets, we analyzed 9944 patients with 33 types of cancers. Significant association between HMGA2 overexpression and poor OS was found in 14 types of cancers. Taken together, consistent results were observed in clear cell renal cell carcinoma, esophageal adenocarcinoma, head and neck cancer, hepatocellular carcinoma, ovarian carcinoma, and pancreatic ductal adenocarcinoma.Conclusion: Our meta-analysis showed the significance of HMGA2 and its prognostic value in various cancers. High level of HMGA2 could be associated with poor OS in patients with clear cell renal cell carcinoma, head and neck cancer, hepatocellular carcinoma and pancreatic ductal adenocarcinoma, but not esophageal adenocarcinoma and ovarian carcinoma.

The Prominent Role of HMGA Proteins in the Early Management of Gastrointestinal Cancers

“…Nonetheless, HMGA levels are frequently upregulated in several different neoplasms, being their overexpression associated with tumor poor prognosis [16]. In this sense, a comprehensive meta-analysis has recently reported the significant impact of high levels of HMGA2 mRNA and/or protein levels on the diminution of cancer patients' overall survival, e.g., of patients affected by renal cell carcinoma, head and neck cancer, hepatocellular carcinoma, and pancreatic ductal adenocarcinoma [17]. HMGA proteins play an important role in cell transformation mainly due to their ability in controlling the expression of genes involved in cell proliferation and invasion control [16].…”

circFAM73A&nbsp;Promotes Cancer Stem Cell-like Properties of Gastric Cancer Through miR-490-3p/HMGA2&nbsp;Positive Feedback and HNRNPK-mediated β-catenin Stabilization.

“…However, HMGA2 expression becomes more restricted as fetal development, partly due to increasing let-7b expression [37] and is particularly low within normal mature tissues, with one exception that it is strongly expressed during spermatogenesis in testis in mice [38]. Intriguingly, independent studies have evidenced that HMGA2 is re-expressed during oncogenesis in a variety of human malignancies [26,27], including gastric cancer, where high expression of HMGA2 correlates with lymph node metastasis, increased TNM stage and reduced patient survival in GC patients [28,39,40]. The aberrant expression of HMGA2 was regulated by diverse mechanism, including chromosomal rearrangements [41] or several noncoding RNA [25].…”

“…High Mobility Group A2 (HMGA2) is a stem cell factor primarily expressed during embryogenesis, with low abundance identi ed in adult human tissues [25]. HMGA2 is aberrantly expressed in several types of cancer, with high levels of HMGA2 associated with a highly malignant phenotype, as it relates with increased tumor proliferation, invasiveness, stemness and reduced survival [26][27][28]. As shown in Fig.…”

MicroRNA‐9 exerts antitumor effects on hepatocellular carcinoma progression by targeting HMGA2

“…Notably, previous studies have provided evidence showing that overexpression of HMGA at the protein level in all tissues of transgenic mice was associated with the development of lymphomas and other tumor types . Furthermore, HMGA was found to be strongly associated with metastasis and poor prognosis in some human cancers . However, the mechanisms underlying the role of HMGA2 in HCC remain unclear.…”