Skip to main content

Advertisement

SpringerLink
Log in

Twist1 Is an Independent Prognostic Factor of Esophageal Squamous Cell Carcinoma and Associated with Its Epithelial–Mesenchymal Transition

  • Gastrointestinal Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Twist1 is known to be involved in epithelial–mesenchymal transition (EMT) and tumor progression. However, its specific role is different depending on the type of cancer. The functional role and clinical significance of Twist1 in esophageal squamous cell carcinoma (ESCC) have been rarely studied.

Methods

We examined Twist1 expression in a total of 199 samples using immunohistochemistry and real-time reverse-transcription polymerase chain reaction (RT-PCR). We also studied the association of Twist1 with EMT of ESCC using tissue samples and in vitro models. In addition, we examined the changes in the whole-genome expression profiles of two ESCC cell lines after inducing upregulation of Twist1.

Results

Twist1 expression was increased in ESCC compared with that of normal esophagus (P < 0.01). We found that expression of Twist1 was strongly associated with poor prognosis on both univariate analysis [relative risk (RR) = 3.019, P = 0.000] and multivariate analysis (RR = 3.131, P = 0.000). In addition, we found that Twist1 expression was strongly correlated with EMT in ESCC tissues. Upregulation of Twist1 induced other EMT inducers in all three esophageal cancer cell lines investigated (TE1, TE8, and TE10). Twist1 also enhanced the migratory and invasive abilities of all three cell lines. Finally, microarray analysis of gene expression in the three ESCC cell lines revealed that Twist1 upregulation affected the expression of mainly cytoskeleton and extracellular matrix-related genes, which are directly related to cell morphology and movement.

Conclusions

Our study indicates that Twist1 is associated with EMT of esophageal squamous cell carcinoma and may be used as a diagnostic and prognostic biomarker in ESCC.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. National Cancer Institute (2010). SEER Cancer Statistics Review 1975-2007. Available at: http://seer.cancer.gov/csr/1975_2007/. Accessed 28 July 2010

  2. Lam AK. Molecular biology of esophageal squamous cell carcinoma. Crit Rev Oncol Hematol. 2000;33:71–90.

    Article  PubMed  CAS  Google Scholar 

  3. Ando N, Ozawa S, Kitagawa Y, Shinozawa Y, Kitajima M. Improvement in the results of surgical treatment of advanced squamous esophageal carcinoma during 15 consecutive years. Ann Surg. 2000;232:225–32.

    Article  PubMed  CAS  Google Scholar 

  4. Adham M, Baulieux J, Mornex F, de La Roche de Bransat E, Ducerf C, Souquet JC, et al. Combined chemotherapy and radiotherapy followed by surgery in the treatment of patients with squamous cell carcinoma of the esophagus. Cancer. 2000;89:946–54.

    Article  PubMed  CAS  Google Scholar 

  5. Puisieux A, Valsesia-Wittmann S, Ansieau S. A twist for survival and cancer progression. Br J Cancer. 2006;94:13–7.

    Article  PubMed  CAS  Google Scholar 

  6. Li L, Cserjesi P, Olson EN. Dermo-1: a novel twist-related bHLH protein expressed in the developing dermis. Dev Biol. 1995;172:280–92.

    Article  PubMed  CAS  Google Scholar 

  7. Chen ZF, Behringer RR. twist is required in head mesenchyme for cranial neural tube morphogenesis. Genes Dev. 1995;9:686–99.

    Article  PubMed  CAS  Google Scholar 

  8. Soo K, O’Rourke MP, Khoo PL, Steiner KA, Wong N, Behringer RR, Tam PP. Twist function is required for the morphogenesis of the cephalic neural tube and the differentiation of the cranial neural crest cells in the mouse embryo. Dev Biol. 2002;247:251–70.

    Article  PubMed  CAS  Google Scholar 

  9. Yang J, Mani SA, Donaher JL, Ramaswamy S, Itzykson RA, Come C, et al. Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis. Cell. 2004;117:927–39.

    Article  PubMed  CAS  Google Scholar 

  10. Hoek K, Rimm DL, Williams KR, Zhao H, Ariyan S, Lin A, et al. Expression profiling reveals novel pathways in the transformation of melanocytes to melanomas. Cancer Res. 2004;64:5270–82.

    Article  PubMed  CAS  Google Scholar 

  11. Niu RF, Zhang L, Xi GM, Wei XY, Yang Y, Shi YR, et al. Up-regulation of Twist induces angiogenesis and correlates with metastasis in hepatocellular carcinoma. J Exp Clin Cancer Res. 2007;26:385–94.

    PubMed  CAS  Google Scholar 

  12. Yan-Qi Z, Xue-Yan G, Shuang H, Yu C, Fu-Lin G, Fei-Hu B, et al. Expression and significance of TWIST basic helix-loop-helix protein over-expression in gastric cancer. Pathology. 2007;39:470–5.

    Article  PubMed  Google Scholar 

  13. Yuen HF, Chua CW, Chan YP, Wong YC, Wang X, Chan KW. Significance of TWIST and E-cadherin expression in the metastatic progression of prostatic cancer. Histopathology. 2007;50:648–58.

    Article  PubMed  Google Scholar 

  14. Ohuchida K, Mizumoto K, Ohhashi S, Yamaguchi H, Konomi H, Nagai E, et al. Twist, a novel oncogene, is upregulated in pancreatic cancer: clinical implication of Twist expression in pancreatic juice. Int J Cancer. 2007;120:1634–40.

    Article  PubMed  CAS  Google Scholar 

  15. Shibata K, Kajiyama H, Ino K, Terauchi M, Yamamoto E, Nawa A, et al. Twist expression in patients with cervical cancer is associated with poor disease outcome. Ann Oncol. 2008;19:81–5.

    Article  PubMed  CAS  Google Scholar 

  16. Song LB, Liao WT, Mai HQ, Zhang HZ, Zhang L, Li MZ, et al. The clinical significance of twist expression in nasopharyngeal carcinoma. Cancer Lett. 2006;242:258–65.

    Article  PubMed  CAS  Google Scholar 

  17. Kwok WK, Ling MT, Lee TW, Lau TC, Zhou C, Zhang X, et al. Up-regulation of TWIST in prostate cancer and its implication as a therapeutic target. Cancer Res. 2005;65:5153–62.

    Article  PubMed  CAS  Google Scholar 

  18. Rosivatz E, Becker I, Specht K, Fricke E, Luber B, Busch R, et al. Differential expression of the epithelial-mesenchymal transition regulators snail, SIP1, and twist in gastric cancer. Am J Pathol. 2002;161:1881–91.

    Article  PubMed  CAS  Google Scholar 

  19. Martin TA, Goyal A, Watkins G, Jiang WG. Expression of the transcription factors snail, slug, and twist and their clinical significance in human breast cancer. Ann Surg Oncol. 2005;12:488–96.

    Article  PubMed  Google Scholar 

  20. Huber MA, Kraut N, Beug H. Molecular requirements for epithelial-mesenchymal transition during tumor progression. Curr Opin Cell Biol. 2005;17:548–58.

    Article  PubMed  CAS  Google Scholar 

  21. Ansieau S, Bastid J, Doreau A, Morel AP, Bouchet BP, Thomas C, et al. Induction of EMT by twist proteins as a collateral effect of tumor-promoting inactivation of premature senescence. Cancer Cell. 2008;14:79–89.

    Article  PubMed  CAS  Google Scholar 

  22. Horikawa T, Yang J, Kondo S, Yoshizaki T, Joab I, Furukawa M, et al. Twist and epithelial-mesenchymal transition are induced by the EBV oncoprotein latent membrane protein 1 and are associated with metastatic nasopharyngeal carcinoma. Cancer Res. 2007;67:1970–8.

    Article  PubMed  CAS  Google Scholar 

  23. Jethwa P, Naqvi M, Hardy RG, Hotchin NA, Roberts S, Spychal R, et al. Overexpression of Slug is associated with malignant progression of esophageal adenocarcinoma. World J Gastroenterol. 2008;14:1044–52.

    Article  PubMed  CAS  Google Scholar 

  24. Yuen HF, Chan YP, Chan KK, Chu YY, Wong ML, Law SY, et al. Id-1 and Id-2 are markers for metastasis and prognosis in oesophageal squamous cell carcinoma. Br J Cancer. 2007;97:1409–15.

    Article  PubMed  CAS  Google Scholar 

  25. Xie F, Li K, Ouyang X. Twist, an independent prognostic marker for predicting distant metastasis and survival rates of esophageal squamous cell carcinoma patients. Clin Exp Metastasis. 2009;26:1025–32.

    Article  PubMed  CAS  Google Scholar 

  26. Sasaki K, Natsugoe S, Ishigami S, Matsumoto M, Okumura H, Setoyama T, et al. Significance of Twist expression and its association with E-cadherin in esophageal squamous cell carcinoma. J Exp Clin Cancer Res. 2009;28:158.

    Article  PubMed  Google Scholar 

  27. Casas E, Kim JH, Bendesky A, Ohno-Machado L, Wolfe CJ, Yang J. Snail2 is an essential mediator of Twist1-induced epithelial mesenchymal transition and metastasis. Cancer Res. 2011;71:245–54.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgment

This study was supported by Samsung Biomedical Research Institute grant C-B0-212-1 and by a grant of the Korea Healthcare technology R&D project, Ministry for Health & Welfare Affairs, Republic of Korea (A092255).

Conflict of interest

There is no commercial interest in the subject of study or source of any financial or material support.

Author information

Authors and Affiliations

  1. Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Gangnam-gu, Seoul, Korea

    Keun-Woo Lee BS, Chang-Ohk Sung MD, Young-hyeh Ko MD & Seok-Hyung Kim MD

  2. Department of Molecular Biology, Samsung Advanced Institute for Health Science and Technology, Sungkyunkwan University, Seoul, Korea

    Jeong Hoon Kim PhD

  3. Department of Pathology, Yanbian University, Yanji, Jilin, China

    Songying Han MD

  4. Experimental Pathology Center, Samsung Cancer Research Institute Samsung Medical Center, Seoul, Korea

    In-Gu Do MD

  5. Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, South Korea

    Sung Hee Um PhD

Authors
  1. Keun-Woo Lee BS
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jeong Hoon Kim PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Songying Han MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Chang-Ohk Sung MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. In-Gu Do MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Young-hyeh Ko MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Sung Hee Um PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Seok-Hyung Kim MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Seok-Hyung Kim MD.

Additional information

K.-W. Lee and J. H. Kim contributed equally to this study.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (PDF 727 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lee, KW., Kim, J.H., Han, S. et al. Twist1 Is an Independent Prognostic Factor of Esophageal Squamous Cell Carcinoma and Associated with Its Epithelial–Mesenchymal Transition. Ann Surg Oncol 19, 326–335 (2012). https://doi.org/10.1245/s10434-011-1867-0

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1245/s10434-011-1867-0

Keywords

Search

Navigation