Skip to main content
SpringerLink
Log in

Clinical Significance of Large Tenascin-C Spliced Variant as a Potential Biomarker for Colorectal Cancer

  • Published:
World Journal of Surgery Aims and scope Submit manuscript

Abstract

Background

Tenascin-C is an extracellular matrix protein forming various types of spliced variants. Low molecule variants are transiently present, but large spliced variants are predominantly overexpressed in proliferative processes or tumorigenesis in some varieties of cancer. However, the detection of the plasma level of large tenascin-C spliced variant (L-Tn-CSV) in colorectal cancer (CRC) has not been clarified. This study was performed to validate elevated plasma L-Tn-CSV levels as a possible biomarker for CRC.

Materials and Methods

Plasma samples were obtained before resection and from time to time postoperatively and stored at −80°C until assay. Plasma L-Tn-CSV levels were evaluated in patients with primary (n = 162) and with recurrent (n = 20) CRC, including 48 healthy volunteers, measured by ELISA.

Results

The average plasma L-Tn-CSV concentrations of patients with primary CRC were 5,260 ± 3,243.3 pg/ml and of patients with recurrent CRC 4,106 ± 2,261.1 pg/ml, which were significantly elevated in comparison with those of healthy volunteers (2,364.3 ± 7,49.6). The sensitivity for detecting CRC using plasma L-Tn-CSV was 56.6%, based on the mean ± 2 SD of the concentrations of healthy controls (3,863.5), which was significantly higher than CEA (40.1%) and CA19-9 (23.6%). No obvious associations were evident between plasma L-Tn-CSV status and values of CEA and CA19-9 respectively. Statistically significant differences in plasma L-Tn-CSV were observed depending on tumor depth, lymph node metastasis, and TNM stage. Negative conversions of plasma L-Tn-CSV levels 6 months after resection were significantly higher in the completely curative resection group than in the non-curative groups (P < 0.001).

Conclusion

The plasma L-Tn-CSV may serve very well as a useful biomarker for tumor staging and postoperative monitoring of preoperatively positive CRC that is independent and exceeds conventional tumor markers.

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

Figure 1.
Figure 2.

Similar content being viewed by others

References

  1. Chiquet-Ehrismann R, Mackie EJ, Pearson CA, et al. Tenascin: an extra cellular matrix protein involved in tissue interactions during fetal development and oncogenesis. Cell 1986;47:131–139

    Article  PubMed  CAS  Google Scholar 

  2. Yoshida T, Yoshimura E, Numata H, et al. Involvement of tenascin-C in proliferation and migration of laryngeal carcinoma cells. Virchows Arch 1999;435:496–500

    Article  PubMed  CAS  Google Scholar 

  3. Jones FS, Jones PL. The tenascin family of ECM glycoproteins: structure, function, and regulation during embryonic development and tissue remodeling. Dev Dyn 2000;218:235–259

    Article  PubMed  CAS  Google Scholar 

  4. Nies DE, Hemesath TJ, Kim JH, et al. The complete cDNA sequence of human hexabrachion (tenascin). A multidomain protein containing unique epidermal growth factor repeats. J Biol Chem 1991;266:2818–2823

    PubMed  CAS  Google Scholar 

  5. Jones PL, Jones FS. Tenascin-C in development and disease: gene regulation and cell function. Matrix Biol 2000;19:581–596

    Article  PubMed  CAS  Google Scholar 

  6. Hindermann W, Berndt A, Borsi L, et al. Synthesis and protein distribution of the unspliced large tenascin-C isoform in oral squamous cell carcinoma. J Pathol 1999;189:475–480

    Article  PubMed  CAS  Google Scholar 

  7. Latijnhouwers MA, de Jongh GJ, Bergers M, et al. Expression of tenascin-C spliced variants by human skin cells. Arch Dermatol Res 2000;292:446–454

    Article  PubMed  CAS  Google Scholar 

  8. Tsunoda T, Inada H, Kalembeyi I, et al. Involvement of large tenascin-C splice variants in breast cancer progression. Am J Pathol 2003;162:1857–1867

    PubMed  CAS  Google Scholar 

  9. Hasegawa M, Hirata H, Sudo A, et al. Tenascin-C concentration in synovial fluid correlates with radiographic progression of knee osteoarthritis. J Rheumatol 2004;31:2021–2026

    PubMed  CAS  Google Scholar 

  10. Emoto K, Yamada Y, Sawada H, et al. Annexin II overexpression correlates with stromal tenascin-C overexpression: a prognostic marker in colorectal carcinoma. Cancer 2001;92:1419–1426

    Article  PubMed  CAS  Google Scholar 

  11. Iskaros BF, Tanaka KE, Hu X, et al. Morphologic pattern of tenascin as a diagnostic biomarker in colon cancer. J Surg Oncol 1997;64:98–101

    Article  PubMed  CAS  Google Scholar 

  12. Dueck M, Riedl S, Hinz U, et al. Detection of tenascin-C isoforms in colorectal mucosa, ulcerative colitis, carcinomas and liver metastases. Int J Cancer 1999;82:477–483

    Article  PubMed  CAS  Google Scholar 

  13. Sobin LH, Witteking C (eds) UICC TNM Classification of Malignant Tumors, 6th edn. New York, Wiley, 2002

    Google Scholar 

  14. Japanese Society for Cancer of the Colon and Rectum. Japanese Classification of Colorectal Carcinoma. First English edn. Tokyo: Kanehara, 1998

    Google Scholar 

  15. Matsumoto K, Hiraiwa N, Yoshiki A et al. Tenascin-C expression and splice variant in habu snake venom-induced glomerulonephritis. Exp Mol Pathol 2002;72:186–195

    Article  PubMed  CAS  Google Scholar 

  16. Joester A, Faissner A. Evidence for combinatorial variability of tenascin-C isoforms and developmental regulation in the mouse central nervous system. J Biol Chem 1999;274:17144–17151

    Article  PubMed  CAS  Google Scholar 

  17. Aufderheide E, Ekblom P. Tenascin during gut development: appearance in the mesenchyme, shift in molecular forms, and dependence on epithelial-mesenchymal interactions. J Cell Biol 1988;107:2341–2349

    Article  PubMed  CAS  Google Scholar 

  18. Jahkola T, Toivonen T, Virtanen I, et al. Tenascin-C expression in invasion border of early breast cancer: a predictor of local and distant recurrence. Br J Cancer 1998;78:1507–1513

    PubMed  CAS  Google Scholar 

  19. Kressner U, Lindmark G, Tomasini-Johansson B, et al. Stromal tenascin distribution as a prognostic marker in colorectal cancer. Br J Cancer 1997;76:526–530

    PubMed  CAS  Google Scholar 

  20. Sugawara I, Hirakoshi J, Kusakabe M, et al. Relationships among tenascin expression, DNA ploidy patterns, and multidrug resistance gene product (P-glycoprotein) in human colon carcinoma. Jpn J Cancer Res 1993;84:703–707

    PubMed  CAS  Google Scholar 

  21. Pilch H, Schaffer U, Schlenger K, et al. Expression of tenascin in human cervical cancer—association of tenascin expression with clinicopathological parameters. Gynecol Oncol 1999;73:415–421

    Article  PubMed  CAS  Google Scholar 

  22. Wiksten JP, Lundin J, Nordling S, et al. Tenascin-C expression correlates with prognosis in gastric cancer. Oncology 2003;64:245–250

    Article  PubMed  CAS  Google Scholar 

  23. Riedl S, Bodenmuller H, Hinz U, et al. Significance of tenascin serum level as tumor marker in primary colorectal carcinoma. Int J Cancer 1995;64:65–69

    PubMed  CAS  Google Scholar 

  24. Takahashi K, Mori T, Yasuno M, et al. Recent strategy of surgery for colonic cancer [in Japanese]. J Jpn Soc Coloproctol 1996;49:1214–1229

    Google Scholar 

  25. Takeda A, Imaseki H, Takayama W, et al. Clinicopathological studies and the significance of combined resection for primary colorectal carcinomas with invasion to the adjacent organs [in Japanese]. J Jpn Soc Clin Surg 1998;59:1222–1228

    Google Scholar 

Download references

Acknowledgements

We are grateful to Dr. Masahiro Maeda, PhD and Dr. Kiyoshi Ishikawa, PhD for excellent technical assistance during this study. This study was supported in part by a Grant-in-Aid for Scientific Research (#16591298, 2003) from the Ministry of Education, Science and Culture of Japan.

Author information

Authors and Affiliations

  1. Department of Surgery and Surgical Oncology, Saitama Medical University, 38 Morohongo, Moroyama, Iruma, 350-0495, Saitama, Japan

    Akihiko Takeda MD, Yoshihide Otani MD, Hiroyoshi Iseki PhD, Hideki Takeuchi MD, Kimiyasu Aikawa MD, Satoru Tabuchi MD, Nozomi Shinozuka MD, Toshiaki Saeki MD, Yasushi Okazaki MD & Isamu Koyama MD

Authors
  1. Akihiko Takeda MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yoshihide Otani MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hiroyoshi Iseki PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hideki Takeuchi MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kimiyasu Aikawa MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Satoru Tabuchi MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Nozomi Shinozuka MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Toshiaki Saeki MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Yasushi Okazaki MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Isamu Koyama MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Akihiko Takeda MD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Takeda, A., Otani, Y., Iseki, H. et al. Clinical Significance of Large Tenascin-C Spliced Variant as a Potential Biomarker for Colorectal Cancer. World J. Surg. 31, 388–394 (2007). https://doi.org/10.1007/s00268-006-0328-6

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00268-006-0328-6

Keywords

Search

Navigation