Skip to main content
Log in

High expression of Transient potential receptor C6 correlated with poor prognosis in patients with esophageal squamous cell carcinoma

  • Original Paper
  • Published:
Medical Oncology Aims and scope Submit manuscript

Abstract

TRPC6 plays a crucial role in the tumor progression of various cancers. The relation between the expression of TRPC6 and clinical prognosis has not been studied yet. Our study was to elucidate the role of TRPC6 in predicting outcomes of patients with esophageal squamous cell carcinoma (ESCC). Fresh frozen samples were collected immediately from 172 patients with ESCC after surgical resection from 2003 to 2008 at Sun Yat-sen University Cancer Center, including 45 pairs of tumor tissues and nontumor tissues. TRPC6 expression was measured by quantitative real-time PCR and Western blotting analyses. TRPC6 mRNA and protein were up-regulated in ESCC tissues when compared with the paired nontumor tissues. High expression of TRPC6 mRNA was associated with the higher pT status (P = 0.016) and pathological staging (P = 0.040). The 5-year disease-specific survival in the high expression of TRPC6 mRNA group (>188.98, n = 81) is poorer than that in low-level expression group (≤188.98, n = 91) (42.1 vs. 62.7 %, P = 0.004). Stratified analysis according to the pathological stage revealed its discernibility on DSS was only pronounced in patients with pStage III (P = 0.015). Cox multivariate analysis revealed that pN category (P < 0.001; Relative risk, 2.897, 95 % CI 1.830–4.585) and the expression of TRPC6 mRNA (P = 0.006; Relative risk, 1.863, 95 % CI 1.196–2.902) were independent prognostic factors. TRPC6 mRNA overexpression correlated with poor prognosis in patients with ESCC and might serve as a novel prognostic biomarker for resected ESCC patients in advanced stage.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127:2893–917.

    Article  PubMed  CAS  Google Scholar 

  2. Wei WQ YJ, Zhang SW, Chen WQ, Qiao YL. Analysis of the esophageal cancer mortality in 2004–2005 and its trends during last 30 years in China. Zhonghua Yu Fang Yi Xue Za Zhi. 2010;44: 398–402.

    Google Scholar 

  3. Jemal A, Siegel R, Xu J, et al. Cancer statistics, 2010. CA Cancer J Clin. 2010;60:277–300.

    Article  PubMed  Google Scholar 

  4. DE Clapham RL, Strubing C. The TRP ion channel family. Nat Rev Neurosci. 2001;2:387–96.

    Article  PubMed  CAS  Google Scholar 

  5. Lehen’kyi V, Prevarskaya N. Oncogenic TRP channels. Adv Exp Med Biol. 2011;704:929–45.

    Article  PubMed  Google Scholar 

  6. Shi Y, Ding X, He ZH, Zhou KC, Wang Q, Wang YZ. Critical role of TRPC6 channels in G2 phase transition and the development of human oesophageal cancer. Gut. 2009;58:1443–50.

    Article  PubMed  CAS  Google Scholar 

  7. Cai R, Ding X, Zhou K, Shi Y, Ge R, Ren G, Jin Y, Wang Y. Blockade of TRPC6 channels induced G2/M phase arrest and suppressed growth in human gastric cancer cells. Int J Cancer. 2009;125:2281–7.

    Article  PubMed  CAS  Google Scholar 

  8. Ding X, He Z, Zhou K, Cheng J, Yao H, Lu D, Cai R, Jin Y, Dong B, Xu Y, Wang Y. Essential role of TRPC6 channels in G2/M phase transition and development of human glioma. J Natl Cancer Inst. 2010;102:1052–68.

    Article  PubMed  CAS  Google Scholar 

  9. Wan Q, Zheng A, Liu X, Chen Y, Han L. Expression of transient receptor potential channel 6 in cervical cancer. Onco Targets Ther. 2012;5:171–6.

    PubMed  Google Scholar 

  10. Dhennin-Duthille I, Gautier M, Faouzi M, et al. High expression of transient receptor potential channels in human breast cancer epithelial cells and tissues correlation with pathological parameters. Cell Physiol Biochem. 2011;28:813–22.

    Article  PubMed  CAS  Google Scholar 

  11. El Boustany C, Bidaux G, Enfissi A, Delcourt P, Prevarskaya N, Capiod T. Capacitative calcium entry and transient receptor potential canonical 6 expression control human hepatoma cell proliferation. Hepatology. 2008;47:2068–77.

    Article  PubMed  Google Scholar 

  12. Yue D, Wang Y, Xiao JY, Wang P, Ren CS. Expression of TRPC6 in benign and malignant human prostate tissues. Asian J Androl. 2009;11:541–7.

    Article  PubMed  CAS  Google Scholar 

  13. Zlobec I, Steele R, Terracciano L, et al. Selecting immunohistochemical cut-off scores for novel biomarkers of progression and survival in colorectal cancer. J Clin Pathol. 2007;60:1112–6.

    Article  PubMed  Google Scholar 

  14. Zhu ZH, Sun BY, Ma Y, et al. Three immunomarker support vector machines-based prognostic classifiers for stage IB non-small-cell lung cancer. J Clin Oncol. 2009;27:1091–9.

    Article  PubMed  Google Scholar 

  15. Rice TW, Blackstone EH, Rusch VW. 7th edition of the AJCC cancer staging manual: esophagus and esophagogastric junction. Ann Surg Oncol. 2010;17:1721–4.

    Article  PubMed  Google Scholar 

  16. Yu Y, Fantozz I, Remillard CV, et al. Enhanced expression of transient receptor potential channels in idiopathic pulmonary arterial hypertension. Proc Natl Acad Sci. 2004;101:13861–6.

    Article  PubMed  CAS  Google Scholar 

  17. Ge R, Tai Y, Sun Y, et al. Critical role of TRPC6 channels in VEGF-mediated angiogenesis. Cancer Lett. 2009;283:43–51.

    Article  PubMed  CAS  Google Scholar 

  18. Zadeh H, MA G, Magnussen CA, et al. VEGF-mediated elevated intracellular calcium and angiogenesis in human microvascular endothelial cells in vitro are inhibited by dominant negative TRPC6. Microcirculation. 2008;15:605–14.

    Article  Google Scholar 

  19. Guilbert A, Dhennin-Duthille I, Hiani YE, Haren N, Khorsi H, Sevestre H, Ahidouch A, Ouadid-Ahidouch H. Expression of TRPC6 channels in human epithelial breast cancer cells. BMC Cancer. 2008;8:125.

    Article  PubMed  Google Scholar 

  20. Thebault S, Flourakis M, Vanoverberghe K, et al. Differential role of transient receptor potential channels in Ca2 + entry and proliferation of prostate cancer epithelial cells. Cancer Res. 2006;66:2038–47.

    Article  PubMed  CAS  Google Scholar 

  21. Berridge MJ, Bootman MD, Roderick HL. Calcium: calcium signalling: dynamics, homeostasis and remodelling. Nat Rev Mol Cell Biol. 2003;4:517–29.

    Article  PubMed  CAS  Google Scholar 

  22. Roderick HL, Cook SJ. Ca2 + signalling checkpoints in cancer: remodelling Ca2 + for cancer cell proliferation and survival. Nat Rev Cancer. 2008;8:361–75.

    Article  PubMed  CAS  Google Scholar 

  23. Ding X, He Z, Shi Y, et al. Targeting TRPC6 channels in oesophageal carcinoma growth. Expert Opin Ther Targets. 2010;14:513–27.

    Article  PubMed  CAS  Google Scholar 

  24. Peng JB, Zhuang L, Berger UV, et al. CaT1 expression correlates with tumor grade in prostate cancer. Biochem Biophys Res Commun. 2001;282:729–34.

    Article  PubMed  CAS  Google Scholar 

  25. Fixemer T, Wissenbach U, Flockerzi V, Bonkhoff H, et al. Expression of the Ca2 + selective cation channel TRPV6 in human prostate cancer: a novel prognostic marker for tumor progression. Oncogene. 2003;22:7858–61.

    Article  PubMed  CAS  Google Scholar 

  26. Lee J, Lee KE, Im YH, Kang WK, Park K, Kim K, Shim YM. Adjuvant chemotherapy with 5-fluorouracil and cisplatin in lymph node-positive thoracic esophageal squamous cell carcinoma. Ann Thorac Surg. 2005;80:1170–5.

    Article  PubMed  Google Scholar 

  27. Ando N, Iizuka T, Ide H, Ishida K, Shinoda M, Nishimaki T, Takiyama W, Watanabe H, Isono K, Aoyama N, et al. Surgery plus chemotherapy compared with surgery alone for localized squamous cell carcinoma of the thoracic esophagus: a Japan Clinical Oncology Group Study–JCOG9204. J Clin Oncol. 2003;21:4592–6.

    Article  PubMed  Google Scholar 

  28. Tepper J, Krasna MJ, Niedzwiecki D, Hollis D, Reed CE, Goldberg R, Kiel K, Willett C, Sugarbaker D, Mayer R. Phase III trial of trimodality therapy with cisplatin, fluorouracil, radiotherapy, and surgery compared with surgery alone for esophageal cancer: CALGB 9781. J Clin Oncol. 2008;26:1086–92.

    Article  PubMed  CAS  Google Scholar 

  29. Gebski V, Burmeister B, Smithers BM, et al. Survival benefits from neoadjuvant chemoradiotherapy or chemotherapy in oesophageal carcinoma: a meta-analysis. Lancet Oncol. 2007;8:226–34.

    Article  PubMed  CAS  Google Scholar 

  30. Sjoquist KM, Burmeister BH, Smithers BM, et al. Survival after neoadjuvant chemotherapy or chemoradiotherapy for resectable oesophageal carcinoma: an updated meta-analysis. Lancet Oncol. 2011;12:681–92.

    Article  PubMed  Google Scholar 

  31. Burmeister BH, Smithers BM, Gebski V, Fitzgerald L, Simes RJ, Devitt P, Ackland S, Gotley DC, Joseph D, Millar J. Surgery alone versus chemoradiotherapy followed by surgery for resectable cancer of the oesophagus: a randomised controlled phase III trial. Lancet Oncol. 2005;6:659–68.

    Article  PubMed  Google Scholar 

  32. van Hagen P, van Lanschot JJ, et al. Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med. 2012;366:2074–84.

    Article  PubMed  Google Scholar 

  33. Geard CR, Schiff PB. Taxol and radiation. J Natl Cancer Inst Monogr. 1993;15:89–94.

    PubMed  Google Scholar 

  34. Tishler RB, Geard CR, et al. Taxol: a novel radiation sensitizer. Int J Radiat Oncol Biol Phys. 1992;22:613–7.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by of Chinese Ministry of Health Key Program Grant (No. 179). We thanks Prof. Xinyuan Guan from Hong Kong University presented us ESCC cell lines. The authors declare not financial disclosures and conflicts of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Yi Hu.

Additional information

Shui-Shen Zhang and Jing Wen are contributed equally to this work and share first authorship.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhang, SS., Wen, J., Yang, F. et al. High expression of Transient potential receptor C6 correlated with poor prognosis in patients with esophageal squamous cell carcinoma. Med Oncol 30, 607 (2013). https://doi.org/10.1007/s12032-013-0607-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12032-013-0607-7

Keywords

Navigation