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Meta-Analysis
. 2017 Apr 4;8(14):22968-22979.
doi: 10.18632/oncotarget.14952.

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

Lorenzo Nicolè  1 , Tiziana Sanavia  2 , Nicola Veronese  3 , Rocco Cappellesso  1   4 , Claudio Luchini  5   6   7 , Paolo Dabrilli  1 , Ambrogio Fassina  1
Affiliations
Meta-Analysis

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

Lorenzo Nicolè et al. Oncotarget. .

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, I2=66%; HR=1.4; 95%CI: 1.19-1.65; p<0.0001; I2=63%) and recurrence of disease (RR = 1.25, 95% CI = 1.1-1.42, p=0.0006, I2=62%); HR=1.52; 95% CI: 1.22-1.89, p=0.0002; I2=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; I2=63%; recurrence of disease: HR=1.52; 95% CI: 1.22-1.89, p=0.0002; I2=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.

Keywords: SALL4; cancer; meta-analysis; prognosis; targeted therapy.

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Conflict of interest statement

CONFLICTS OF INTEREST

The authors declare that they have no conflicts of interest.

Figures

Figure 1A
Figure 1A. Forest plot of the association between associating the presence/absence of SALL4 with and all-cause mortality
Abbreviations: CI: Confidence Interval, SALL4: Spalt-Like Transcription Factor 4, RE: Random-Effects.
Figure 1B
Figure 1B. Forest plot of the association between associating the presence/absence of SALL4 with recurrence of cancer
Abbreviations: CI: Confidence Interval, SALL4: Spalt-Like Transcription Factor 4, RE: Random-Effects.
Figure 2A
Figure 2A. Forest plot of the association associating the presence/absence of between SALL4 with and all-cause mortality using the hazard ratios adjusted for the maximum number of potential confounders available in each paper
Abbreviations: CI: Confidence Interval, SALL4: Spalt-Like Transcription Factor 4, RE: Random-Effects.
Figure 2B
Figure 2B. Forest plot of the association associating the presence/absence of between SALL4 with recurrence of cancer using the hazard ratios adjusted for the maximum number of potential confounders available in each paper
Abbreviations: CI: Confidence Interval, SALL4: Spalt-Like Transcription Factor 4, RE: Random-Effects.
Figure 3
Figure 3. Funnel plots indicating that the publication bias was unlikely across all the outcomes, except for the relative risk in all-cause mortality
See this image and copyright information in PMC

References

    1. Lim CY, Tam WL, Zhang J, Ang HS, Jia H, Lipovich L, Ng HH, Wei CL, Sung WK, Robson P, Yang H, Lim B. Sall4 regulates distinct transcription circuitries in different blastocyst-derived stem cell lineages. Cell Stem Cell. 2008;3:543–54. - PubMed
    1. Zhang J, Tam WL, Tong GQ, Wu Q, Chan HY, Soh BS, Lou Y, Yang J, Ma Y, Chai L, Ng HH, Lufkin T, Robson P, Lim B. Sall4 modulates embryonic stem cell pluripotency and early embryonic development by the transcriptional regulation of Pou5f1. Nat Cell Biol. 2006;8:1114–23. - PubMed
    1. Wang J, Rao S, Chu J, Shen X, Levasseur DN, Theunissen TW, Orkin SH. A protein interaction network for pluripotency of embryonic stem cells. Nature. 2006;444:364–68. - PubMed
    1. Miettinen M, Wang Z, McCue PA, Sarlomo-Rikala M, Rys J, Biernat W, Lasota J, Lee YS. SALL4 expression in germ cell and non-germ cell tumors: a systematic immunohistochemical study of 3215 cases. Am J Surg Pathol. 2014;38:410–20. - PMC - PubMed
    1. Gao C, Kong NR, Li A, Tatetu H, Ueno S, Yang Y, He J, Yang J, Ma Y, Kao GS, Tenen DG, Chai L. SALL4 is a key transcription regulator in normal human hematopoiesis. Transfusion. 2013;53:1037–49. - PMC - PubMed