Journal of Cancer Research and Clinical Oncology

, Volume 141, Issue 2, pp 229–235 | Cite as

SALL4 as a new biomarker for early colorectal cancers

  • Sima Ardalan Khales
  • Mohammad Reza Abbaszadegan
  • Abbas Abdollahi
  • Reza Raeisossadati
  • Mohsen Fallah Tousi
  • Mohammad Mahdi Forghanifard
Original Article – Cancer Research

Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusion

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.

Keywords

SALL4 CEA Colorectal cancer Prognosis marker 

References

  1. 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
  2. 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
  3. 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
  4. Chen X, Ba Y, Ma L, Cai X, Yin Y, Wang K, Guo J, Zhang Y, Chen J, Guo X et al (2008) Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res 18(10):997–1006PubMedCrossRefGoogle Scholar
  5. De Roock W, Biesmans B, De Schutter J, Tejpar S (2009) Clinical biomarkers in oncology: focus on colorectal cancer. Mol Diagn Ther 13(2):103–114PubMedCrossRefGoogle Scholar
  6. Duffy MJ (2001) Carcinoembryonic antigen as a marker for colorectal cancer: is it clinically useful? Clin Chem 47:624–630PubMedGoogle Scholar
  7. Eleftheriadis N, Papaloukas C, Pistevou-Gompaki K (2009) Diagnostic value of serum tumor markers in asymptomatic individuals. J Buon 14(4):707–710PubMedGoogle Scholar
  8. Forghanifard MM, Moghbeli M, Raeisossadati R, Tavassoli A, Mallak AJ, Boroumand-Noughabi S, Abbaszadegan MR (2013) Role of SALL4 in the progression and metastasis of colorectal cancer. J Biomed Sci 20:6PubMedCentralPubMedCrossRefGoogle Scholar
  9. Forghanifard MM, Ardalan Khales S, Javdani-Mallak A, Rad A, Farshchian M, Abbaszadegan MR (2014) Stemness state regulators SALL4 and SOX2 are involved in progression and invasiveness of esophageal squamous cell carcinoma. Med Oncol 31(4):922PubMedCrossRefGoogle Scholar
  10. Grutzmann R, Molnar B, Pilarsky C, Habermann JK, Schlag PM, Saeger HD, Miehlke S, Stolz T, Model F, Roblick UJ et al (2008) Sensitive detection of colorectal cancer in peripheral blood by septin 9 DNA methylation assay. PLoS one 3(11):e3759PubMedCentralPubMedCrossRefGoogle Scholar
  11. Huang Z, Huang D, Ni S, Peng Z, Sheng W, Du X (2010) Plasma microRNAs are promising novel biomarkers for early detection of colorectal cancer. Int J Cancer 127(1):118–126PubMedCrossRefGoogle Scholar
  12. Itou J, Toi M (2014) Function of the Developmental Transcription Factor SALL4 in Cancer. J Carcinog Mutagen 5(159):2Google Scholar
  13. Jain KK (2007) Cancer biomarkers: current issues and future directions. Curr Opin Mol Ther 9(6):563–571PubMedGoogle Scholar
  14. Jurgens G (1988) Head and tail development of the Drosophila embryo involves spalt, a novel homeotic gene. EMBO J 7(1):189–196PubMedCentralPubMedGoogle Scholar
  15. Kanavos P, Schurer W (2009) The dynamics of colorectal cancer management in 17 countries. Eur J Health Econ 10(Suppl 1):S115–S129Google Scholar
  16. Kim DH, Pickhardt PJ, Taylor AJ, Leung WK, Winter TC, Hinshaw JL, Gopal DV, Reichelderfer M, Hsu RH, Pfau PR (2007) CT colonography versus colonoscopy for the detection of advanced neoplasia. N Engl J Med 357(14):1403–1412PubMedCrossRefGoogle Scholar
  17. Kim HJ, Yu MH, Kim H, Byun J, Lee C (2008) Noninvasive molecular biomarkers for the detection of colorectal cancer. BMB Rep 41(10):685–692PubMedCrossRefGoogle Scholar
  18. 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
  19. Lee BB, Lee EJ, Jung EH et al (2009) Aberrant methylation of APC, MGMT, RASSF2A, and Wif1 genes in plasma as a biomarker for early detection of colorectal cancer. Clin Cancer Res 15:6185–6191PubMedCrossRefGoogle Scholar
  20. 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
  21. Lim CY, Tam WL, Zhang J, Ang HS, Jia H, Lipovich L, Ng HH, Wei CL, Sung WK, Robson P et al (2008) Sall4 regulates distinct transcription circuitries in different blastocyst-derived stem cell lineages. Cell Stem Cell 3:543–554PubMedCrossRefGoogle Scholar
  22. Mandel JS (2008) Screening for colorectal cancer. Gastroenterol Clin North Am 37(1):97–115PubMedCrossRefGoogle Scholar
  23. Migliore L, Migheli F, Spisni R, Coppede F (2011) Genetics, cytogenetics, and epigenetics of colorectal cancer. J Biomed Biotechnol: 792362Google Scholar
  24. Newton KF, Newman W, Hill J (2012) Review of biomarkers in colorectal cancer. Colorectal Dis 14(1):3–17PubMedCrossRefGoogle Scholar
  25. 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
  26. Schmittgen TD, Livak KJ (2008) Analyzing real-time PCR data by the comparative (CT) method. Nat Protoc 3:1101–1108PubMedCrossRefGoogle Scholar
  27. Shuai XZD, Shen T, Wu Y, Zhang J, Wang X, Li Q (2009) Overexpression of the novel oncogene SALL4 and activation of the Wnt/beta-catenin pathway in myelodysplastic syndromes. Cancer Genet Cytogenet 194:119–124PubMedCrossRefGoogle Scholar
  28. Siegel R, Naishadham D, Jemal A (2012) Cancer statistics, 2012. CA Cancer J Clin 62(1):10–29PubMedCrossRefGoogle Scholar
  29. Siegel R, Desantis C, Jemal A (2014) Colorectal cancer statistics, 2014. CA Cancer J Clin 64(2):104–117PubMedCrossRefGoogle Scholar
  30. Summers T, Langan RC, Nissan A, Brucher BL, Bilchik AJ, Protic M, Daumer M, Avital I, Stojadinovic A (2013) Serum-based DNA methylation biomarkers in colorectal cancer: potential for screening and early detection. J Cancer 4(3):210–216PubMedCentralPubMedCrossRefGoogle Scholar
  31. Ueno S, Lu J, He J, Li A, Zhang X, Ritz J, Silberstein LE, Chai L (2014) Aberrant expression of SALL4 in acute B cell lymphoblastic leukemia: Mechanism, function, and implication for a potential novel therapeutic target. Exp Hematol 42(4):307–316PubMedCentralPubMedCrossRefGoogle Scholar
  32. Winawer S, Fletcher R, Rex D, Bond J, Burt R, Ferrucci J, Ganiats T, Levin T, Woolf S, Johnson D et al (2003) Colorectal cancer screening and surveillance: clinical guidelines and rationale-Update based on new evidence. Gastroenterology 124(2):544–560PubMedCrossRefGoogle Scholar
  33. Xu D, Li XF, Zheng S, Jiang WZ (2006) Quantitative real-time RT-PCR detection for CEA, CK20 and CK19 mRNA in peripheral blood of colorectal cancer patients. J Zhejiang Univ Sci B 7(6):445–451PubMedCentralPubMedCrossRefGoogle Scholar
  34. Yang J, Chai L, Fowles TC, Alipio Z, Xu D, Fink LM, Ward DC, Ma Y (2008) Genome-wide analysis reveals Sall4 to be a major regulator of pluripotency in murine-embryonic stem cells. Proc Natl Acad Sci USA 105:19756–19761PubMedCentralPubMedCrossRefGoogle Scholar
  35. 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
  36. 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
  37. Zieglschmid V, Hollmann C, Bocher O (2005) Detection of disseminated tumor cells in peripheral blood. Crit Rev Clin Lab Sci 42(2):155–196PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Sima Ardalan Khales
    • 1
  • Mohammad Reza Abbaszadegan
    • 2
  • Abbas Abdollahi
    • 3
  • Reza Raeisossadati
    • 4
  • Mohsen Fallah Tousi
    • 5
  • Mohammad Mahdi Forghanifard
    • 6
  1. 1.Division of Human Genetics, Immunology Research Center, Avicenna Research InstituteMashhad University of Medical SciencesMashhadIran
  2. 2.Medical Genetics Research Center, Medical SchoolMashhad University of Medical SciencesMashhadIran
  3. 3.Department of General Surgery, Omid HospitalMashhad University of Medical SciencesMashhadIran
  4. 4.Núcleo de Cognição e Sistemas Complexos, Centro de Matemática, Computação e CogniçãoUniversidade Federal do ABCSanto AndréBrazil
  5. 5.Department of General Surgery, Emam Reza HospitalMashhad University of Medical SciencesMashhadIran
  6. 6.Department of BiologyDamghan Branch, Islamic Azad UniversityDamghanIran

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