CarcinogenesisHigh mobility group A protein-2 as a tumor cancer diagnostic and prognostic marker: a systematic review and meta-analysisThi-Hai Pham, Yena,,*; Utuama, Ovieb,,*; Thomas, Claire E.c,,d,,*; Park, Jong A.e; La Vecchia, Carlof; Risch, Harvey A.g,,h; Tran, Chi Thi-Dui; Le, Thanh V.j; Boffetta, Paolok; Raskin, Leonl,,#; Luu, Hung N.c,,d,,#Author Information aDepartment of Rehabilitation, Vinmec Healthcare System, Hanoi, Vietnam bDepartment of Epidemiology and Biostatistics, College of Public Health, University of South Florida, Tampa, Florida cDepartment of Epidemiology, University of Pittsburgh Graduate School of Public Health dDivision of Cancer Control and Population Sciences, University of Pittsburgh Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania eDepartment of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA fDepartment of Clinical Sciences and Community Health, University of Milan, Milan, Italy gDepartment of Chronic Disease Epidemiology, Yale School of Public Health, Yale University hYale Cancer Center, New Haven, Connecticut, USA iVietnam Colorectal Cancer and Polyps Research, Vinmec Healthcare System jDepartment of Hepatobiliary and Pancreatic Surgery, 108 Hospital, Hanoi, Vietnam kTisch Cancer Institute, Icahn School of Medicine, Mount Sinai School of Medicine, New York, New York lCenter for Observational Research, Amgen Inc., Thousand Oaks, California, USA *Yen Thi-Hai Pham, Ovie Utuama, and Claire E. Thomas contributed equally as the co-first authors. #Leon Raskin and Hung N. Luu contributed equally as the co-senior authors. Received 25 July 2019 Accepted 31 March 2020 In summary, our systematic review included 42 studies that demonstrated that HMGA2 was overexpressed (i.e. more than 64%) in all 15 types cancers and HMGA2 overexpression was significantly associated with reduced survival. We also found a trend towards association between HMGA2 expression and cancer recurrence, an indication of promising tumor marker for prognostic predictive value. Since prior effort has shown that using HMGA2 in combination with other tumor marker would enhance test accuracy, we believe that HMGA2 would be a promising tumor pronostic marker in the era of precision medicine. Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (www.eurjcancerprev.com). Correspondence to Hung N. Luu, MD, PhD, UPMC Hillman Cancer Center, UPMC Cancer Pavilion, Suite 4C, Room 466, 5150 Centre Avenue, Pittsburgh, PA 15232, USA, Tel: +412 623 3386; fax: +1 412 623 3303; e-mail: [email protected] European Journal of Cancer Prevention: November 2020 - Volume 29 - Issue 6 - p 565-581 doi: 10.1097/CEJ.0000000000000602 Buy SDC Metrics Abstract High mobility group A protein-2 (HMGA2) is an architectural transcription factor that binds to the A/T-rich DNA minor groove and is responsible for regulating transcriptional activity of multiple genes indirectly through chromatin change and assembling enhanceosome. HMGA2 is overexpressed in multiple tumor types, suggesting its involvement in cancer initiation and progression, thus, making it an ideal candidate for cancer diagnostic and prognostic. We performed a systematic review to examine the role of HMGA2 as a universal tumor cancer diagnostic and prognostic marker. We used Reporting Recommendations for Tumor Marker Prognostic Studies to systematically search OvidMedline, PubMed, and the Cochrane Library for English language studies, published between 1995 and June 2019. Meta-analysis provided pooled risk estimates and their 95% confidence intervals (CIs) for an association between overall survival and recurrence of cancers for studies with available estimates. We identified 42 eligible studies with a total of 5123 tumor samples in 15 types of cancer. The pooled percentage of HMGA2 gene expression in tumor samples was 65.14%. Meta-analysis showed that cancer patients with HMGA2 positive have significantly reduced survival, compared to patients without HMGA2 gene [pooled-hazard ratio (HR) = 1.85, 95% CI 1.48–2.22]. There was a positive association between cancer patients with HMGA2 overexpression and cancer recurrence though this association did not reach significance (pooled-HR = 1.44, 95% CI 0.80–2.07). Overexpression of HMGA2 was found in 15 types of cancer. There was an association between HMGA2 overexpression with reduced survival of cancer patients. HMGA2 is thus considered a promising universal tumor marker for prognostics. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.