Oncofetal gene SALL4 and prognosis in cancer: A systematic review with meta-analysis

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// Lorenzo Nicolè 1, * , Tiziana Sanavia 2, * , Nicola Veronese 3 , Rocco Cappellesso 1, 7 , Claudio Luchini 4, 5, 6 , Paolo Dabrilli 1 , Ambrogio Fassina 1 1 Department of Medicine, Surgical Pathology & Cytopathology Unit, University of Padova, Padova, Italy 2 Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA 3 National Research Council, Neuroscience Institute, Aging Branch, Padova, Italy 4 Department of Pathology and Diagnostics, University and Hospital Trust of Verona, Verona, Italy 5 ARC-NET Research Center, University and Hospital Trust of Verona, Verona, Italy 6 Department of Pathology, Santa Chiara Hospital, Trento, Italy 7 Pathological Anatomy and Histology Unit, Veneto Institute of Oncology, Padova, Italy * These authors have contributed equally to this work Correspondence to: Ambrogio Fassina, email: ambrogio.fassina@unipd.it Keywords: SALL4, cancer, prognosis, meta-analysis, targeted therapy Received: April 05, 2016 Accepted: January 06, 2017 Published: February 01, 2017 ABSTRACT The Spalt-Like Transcription Factor 4 (SALL4) oncogene plays a central function in embryo-fetal development and is absent in differentiated tissues. Evidence suggests that it can be reactivated in several cancers worsening the prognosis. We aimed at investigating the risk associated with SALL4 reactivation for all-cause mortality and recurrence in cancer using the current literature. A PubMed and SCOPUS search until 1st September 2016 was performed, focusing on perspective studies reporting prognostic parameters in cancer data. In addition, 17 datasets of different cancer types from The Cancer Genome Atlas were considered. A total of 9,947 participants across 40 cohorts, followed-up for about 5 years on average, were analyzed comparing patients showing SALL4 presence (SALL4+, n = 1,811) or absence (SALL4-, n = 8,136). All data were summarised using risk ratios (RRs) for the number of deaths/recurrences and hazard ratios (HRs) for the time-dependent risk related to SALL4+, adjusted for potential confounders. SALL4+ significantly increased overall mortality (RR = 1.34, 95% confidence intervals (CI)=1.21-1.48, p<0.0001, I 2 =66%; HR=1.4; 95%CI: 1.19-1.65; p<0.0001; I 2 =63%) and recurrence of disease (RR = 1.25, 95% CI = 1.1-1.42, p=0.0006, I 2 =62%); HR=1.52; 95% CI: 1.22-1.89, p=0.0002; I 2 =69%) compared to SALL4-. Moreover, SALL4 remained significantly associated with poor prognosis even using HRs adjusted for potential confounders (overall mortality: HR=1.4; 95%CI: 1.19-1.65; p<0.0001; I 2 =63%; recurrence of disease: HR=1.52; 95% CI: 1.22-1.89, p=0.0002; I 2 =69%). These results suggest that SALL4 expression increases both mortality and recurrence of cancer, confirming this gene as an important prognostic marker and a potential target for personalized medicine.