SALL4 as a new biomarker for early colorectal cancers
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Colorectal cancer (CRC) is one of the most common causes of cancer-related death worldwide, and there is an urgent need to identify critical diagnostic and prognostic factors for early detection of the disease. Our aim in this study was to elucidate absolute copy number of SALL4 mRNA in the peripheral blood and serum of CRC patients to evaluate its probable prognostic or diagnostic value for CRC.
Peripheral mononuclear cells from 111 cases were examined using absolute quantitative real-time RT-PCR to assess the exact copy number of SALL4 and CEA mRNA. Receiver operator characteristic (ROC) curves were also depicted to detect the sensitivity and specificity of SALL4 mRNA.
The blood copy number of SALL4 in recruited CRC patients was significantly higher than healthy controls (p = 0.0001). This high copy number was not only inversely associated with the depth of tumor invasion (p = 0.045), but also was significantly correlated with the high grade of tumor differentiation (p = 0.029) and sex (p = 0.027). Furthermore, the copy number of SALL4 was elevated in all examined serum samples (p = 0.0001) in significant association with high grade of tumor differentiation (p = 0.026) and patients’ age (p = 0.012). ROC analysis indicated 96.1 and 95 % sensitivity and specificity of SALL4 for CRC screening, respectively.
Early detection of CRC is directly correlated to improved outcomes, increased survival rates and reduced mortality. Our results can introduce SALL4 as a critical biomarker for efficient screening of patients to detect early stages of CRC.
KeywordsSALL4 CEA Colorectal cancer Prognosis marker
This study was supported by a grant from Vice chancellor of Mashhad University of Medical Sciences (#911253).
Conflict of interest
The authors declared no competing interests.
- Ahmedin Jemal D, PhD1, Freddie Bray P, Melissa M. Center M, Jacques Ferlay M, Elizabeth Ward P, David Forman P. 2011. Global Cancer Statistics. CA Cancer J Clin 61:69–90Google Scholar
- Al-Baradie R, Yamada K, St Hilaire C, Chan WM, Andrews C, McIntosh N, Nakano M, Martonyi EJ, Raymond WR, Okumura S et al (2002) Duane radial ray syndrome (Okihiro syndrome) maps to 20q13 and results from mutations in SALL4, a new member of the SAL family. Am J Hum Genet 71(5):1195–1199PubMedCentralPubMedCrossRefGoogle Scholar
- Andersen CL, Jensen JL, Orntoft TF (2004) Normalization of real-time quantitative reverse transcription-PCR data: a model-based variance estimation approach to identify genes suited for normalization, applied to bladder and colon cancer data sets. Cancer Res 64(15):5245–5250PubMedCrossRefGoogle Scholar
- Itou J, Toi M (2014) Function of the Developmental Transcription Factor SALL4 in Cancer. J Carcinog Mutagen 5(159):2Google Scholar
- Kanavos P, Schurer W (2009) The dynamics of colorectal cancer management in 17 countries. Eur J Health Econ 10(Suppl 1):S115–S129Google Scholar
- Kohlhase J, Schuh R, Dowe G, Kühnlein RP, Jäckle H, Schroeder B, Schulz-Schaeffer W, Kretzschmar HA, Köhler A, Müller U et al (1996) Isolation, characterization, and organ-specific expression of two novel human zinc finger genes related to the Drosophila gene spalt. Genomics 38:291–298PubMedCrossRefGoogle Scholar
- Levin B, Lieberman DA, McFarland B, Andrews KS, Brooks D, Bond J, Dash C, Giardiello FM, Glick S, Johnson D et al (2008) Screening and surveillance for the early detection of colorectal cancer and adenomatous polyps, 2008: a joint guideline from the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology. Gastroenterology 134(5):1570–1595PubMedCrossRefGoogle Scholar
- Migliore L, Migheli F, Spisni R, Coppede F (2011) Genetics, cytogenetics, and epigenetics of colorectal cancer. J Biomed Biotechnol: 792362Google Scholar
- Raeisossadati R, Farshchian M, Ganji A, Tavassoli A, Velayati A, Dadkhah E, Chavoshi S, Bahar MM, Memar B, Rajabi Mashhadi MT et al (2011) Quantitative analysis of TEM-8 and CEA tumor markers indicating free tumor cells in the peripheral blood of colorectal cancer patients. Int J Colorectal Dis 26(10):1265–1270PubMedCrossRefGoogle Scholar
- Yuri S, Fujimura S, Nimura K, Takeda N, Toyooka Y, Fujimura Y, Aburatani H, Ura K, Koseki H, Niwa H et al (2009) Sall4 is essential for stabilization, but not for pluripotency, of embryonic stemcells by repressing aberrant trophectoderm gene expression. Stem Cells 27:796–805PubMedCrossRefGoogle Scholar
- Zhang L, Xu Z, Xu X, Zhang B, Wu H, Wang M, Zhang X, Yang T, Cai J, Yan Y et al (2013) SALL4, a novel marker for human gastric carcinogenesis and metastasis. Oncogene. doi: 10.1038/onc.2013.495