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As a Novel Prognostic Marker, Cysteine/histidine-rich 1 (CYHR1) is a Therapeutic Target in Patients with Esophageal Squamous Cell Carcinoma

  • Translational Research and Biomarkers
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Cysteine/histidine-rich 1 (CYHR1) was first discovered in a yeast two-hybrid screen with murine galectin-3, and no previous reports have described a relationship between the CYHR1 gene and human cancer. The current study evaluated the role and significance of CYHR1 in esophageal cancer.

Methods

The human esophageal squamous cell carcinoma (ESCC) cell line TE-8 and the CYHR1 knock-down cell line TE-8/small interfering (si)-CYHR1 were used for in vitro and in vivo assays. For clinical study, ESCC tissues (n = 104) were used.

Results

Compared with parental cells, TE-8/si-CYHR1 cells had suppressed proliferation and invasion activities. In the in vivo assay, the tumors from TE-8 cells treated with si-CYHR1 had abrogated tumorigenicity. In the clinical study, the expression of CYHR1 mRNA was associated with lymph node metastasis and stage and shown to be an independent prognostic factor.

Conclusions

As the findings show, CYHR1 may represent not only a valuable prognostic marker but also a therapeutic target for ESCC patients.

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References

  1. [globocan.iarc.fr] GLOBOCAN database, 2008.

  2. Jemal A, Bray F, Center MM, et al. Global cancer statistics. CA Cancer J Clin. 2011;61:69–70.

    Article  PubMed  Google Scholar 

  3. Bancewicz J, Clark P, Smith D, et al. Med Res Council Oesophageal Cnc. Surgical resection with or without preoperative chemotherapy in oesophageal cancer: a randomized controlled trial. Lancet. 2002;359:1727–33.

    Article  Google Scholar 

  4. Kelsen DP, Ginsberg R, Pajak TF, et al. Chemotherapy followed by surgery compared with surgery alone for localized esophageal cancer. N Engl J Med. 1998;339:1979–84.

    Article  CAS  PubMed  Google Scholar 

  5. Sobin LH, Wittekind C. International Union Against Cancer (UICC) TNM Classification of Malignant Tumours, vol. 6. New York: Wiley; 2002.

  6. Sobin LH, Gospodarowicz MK, Wittekind C. International Union Against Cancer (UICC) TNM Classification of Malignant Tumours. vol. 7. New York: Wiley; 2010.

  7. Tanaka F, Yamamoto K, Suzuki S, et al. Strong interaction between the effects of alcohol consumption and smoking on oesophageal squamous cell carcinoma among individuals with ADH1B and/or ALDH2 risk alleles. Gut. 2010;59:1457–64. doi:10.1136/gut.2009.205724

    Article  CAS  PubMed  Google Scholar 

  8. Ohta M, Mimori K, Fukuyoshi Y, et al. Clinical significance of the reduced expression of G protein gamma 7 (GNG7) in oesophageal cancer. Br J Cancer. 2008;98:410–17. doi:10.1038/sj.bjc.6604124

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Yoshinaga K, Mimori K, Inoue H, et al. Activin A enhances MMP-7 activity via the transcription factor AP-1 in an esophageal squamous cell carcinoma cell line. Int J Oncol. 2008;33:453–9.

    CAS  PubMed  Google Scholar 

  10. Kita Y, Mimori K, Iwatsuki M, et al. STC2: A predictive marker for lymph node metastasis in esophageal squamous-cell carcinoma. Ann Surg Oncol. 2011;18:261–72. doi:10.1245/s10434-010-1271-1

    Article  PubMed  Google Scholar 

  11. Nishida N, Mimori K, Yokobori T, et al. FOXC2 is a novel prognostic factor in human esophageal squamous cell carcinoma. Ann Surg Oncol. 2011;18:535–42. doi:10.1245/s10434-010-1274-y

    Article  PubMed  Google Scholar 

  12. Kogo R, Mimori K, Tanaka F, et al. FBXO31 determines poor prognosis in esophageal squamous cell carcinoma. Int J Oncol. 2011;39:155–9. doi:10.3892/ijo.2011.1018

    PubMed  Google Scholar 

  13. Yokobori T1, Mimori K, Iwatsuki M, et al. Copy number loss of FBXW7 is related to gene expression and poor prognosis in esophageal squamous cell carcinoma. Int J Oncol. 2012;41:253–9. doi:10.3892/ijo.2012.1436.

  14. Sudo T, Iwaya T, Nishida N, et al. Expression of mesenchymal markers vimentin and fibronectin: the clinical significance in esophageal squamous cell carcinoma. Ann Surg Oncol. 2013;20(Suppl 3):S324–35. doi:10.1245/s10434-012-2418-z

    Article  PubMed  Google Scholar 

  15. Sawada G, Takahashi Y, Niida A, et al. Loss of CDCP1 expression promotes invasiveness and poor prognosis in esophageal squamous cell carcinoma. Ann Surg Oncol. 2014.

  16. Menon RP, Strom M, Hughes RC. Interaction of a novel cysteine and histidine-rich cytoplasmic protein with galectin-3 in a carbohydrate-independent manner. FEBS Lett. 2000;470:227–31.

    Article  CAS  PubMed  Google Scholar 

  17. Bawumia S, Barboni EA, Menon RP, et al. Specificity of interactions of galectin-3 with Chrp, a cysteine- and histidine-rich cytoplasmic protein. Biochimie. 2003;85:189–94.

    Article  CAS  PubMed  Google Scholar 

  18. Calvo JH, Marcos S, Beattie AE, et al. Linkage mapping of ovine cysteine and histidine-rich protein gene (CYHR1) to chromosome 9. Anim Genet. 2004;35:263–4.

    Article  CAS  PubMed  Google Scholar 

  19. Kaupe B, Kollers S, Fries R, et al. Mapping of CYB11B and a putative CYHR1 paralogous gene to bovine chromosome 14 by FISH. Anim Genet. 2004;35:478–9.

    Article  CAS  PubMed  Google Scholar 

  20. Nishimura T, Hashimoto Y, Katayama M, et al. Molecular and cellular features of esophageal cancer cells. J Cancer Res Clin Oncol. 1993;119:441–9.

    Article  Google Scholar 

  21. Shimada Y, Imamura M, Wagata T, et al. Characterization of 21newly established esophageal cancer cell lines. Cancer. 1992;69:277–84.

    Article  CAS  PubMed  Google Scholar 

  22. Berg JM. Potential metal-binding domains in nucleic acid binding proteins. Science. 1986;232:485–7.

    Article  CAS  PubMed  Google Scholar 

  23. Frankel AD, Berg JM, Pabo CO. Metal-dependent folding of a single zinc finger from transcription factor IIIA. Proc Natl Acad Sci USA. 1987;84:4841–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Parraga G, Horvath SJ, Eisen A, et al. Zinc-dependent structure of a single-finger domain of yeast ADR1. Science. 1988;241:1489–92.

    Article  CAS  PubMed  Google Scholar 

  25. Aronson BD, Somerville RL, Epperly BR, et al. The primary structure of Escherichia coli l-threonine dehydrogenase. J Biol Chem. 1989;264:5226–32.

    CAS  PubMed  Google Scholar 

  26. Ly-Huynh JD, Lieu KG, Major AT, et al. Importin alpha2-interacting proteins with nuclear roles during mammalian spermatogenesis. Biol Reprod. 2011;85:1191–202. doi:10.1095/biolreprod.111.091686

    Article  CAS  PubMed  Google Scholar 

  27. LaCasse EC, Baird S, Korneluk RG. The inhibitors of apoptosis (IAPs) and their emerging role in cancer. Oncogene. 1998;17:3247–59.

    Article  PubMed  Google Scholar 

  28. Ambrosini G, Aidida C, Altieri DC. A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma. Nat Med. 1997;3:917–21.

    Article  CAS  PubMed  Google Scholar 

  29. Akahani S, Nangia-Makker P, Inohara H, et al. Galectin-3: A novel antiapoptotic molecule with a functional BH1 (NWGR) domain of Bcl-2 family. Cancer Res. 1997;57:5272–6.

    CAS  PubMed  Google Scholar 

  30. Subramanian A, Tamayo P, Mootha VK, et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci USA. 2005;102:15545–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Mizuno H, Kitada K, Nakai K, Sarai A. PrognoScan: A new database for meta-analysis of the prognostic value of genes. BMC Med Genomics. 2009;2:18.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

This study was supported by a Grant-in-Aid for Scientists from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (Grant No. 24591954).

Conflict of Interest

There are no conflicts of interest.

Author information

Authors and Affiliations

  1. Department of Surgical Oncology, Digestive Surgery, Graduate School of Medical Sciences, Kagoshima University, Kagoshima, Japan

    Ryosuke Desaki MD, Hiroshi Okumura MD, Kan Tanabe MD, Yoshiaki Kita MD, PhD, Yasuto Uchikado MD, PhD, Takaaki Arigami MD, PhD, Yoshikazu Uenosono MD, PhD, Sumiya Ishigami MD, PhD & Shoji Natsugoe MD, PhD

  2. Department of Surgery, Kyushu University Beppu Hospital, Beppu, Oita, Japan

    Genta Sawada MD, Hisateru Komatsu MD & Koshi Mimori MD, PhD

  3. Department of Clinical Pharmacy and Pharmacology, Graduate School of Medicine, Kagoshima University, Kagoshima, Japan

    Ryuji Ikeda PhD

  4. Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Osaka University, Suita, Osaka, Japan

    Masaki Mori MD, PhD, FACS

  5. Education Center for Doctors in Remote Islands and Rural Areas, Graduate School of Medical Sciences, Kagoshima University, Kagoshima, Japan

    Tetsuhiro Owaki MD, PhD

Authors
  1. Ryosuke Desaki MD
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  2. Genta Sawada MD
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  5. Kan Tanabe MD
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  6. Hisateru Komatsu MD
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  7. Koshi Mimori MD, PhD
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  8. Masaki Mori MD, PhD, FACS
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  9. Yoshiaki Kita MD, PhD
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  10. Yasuto Uchikado MD, PhD
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  11. Takaaki Arigami MD, PhD
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  12. Yoshikazu Uenosono MD, PhD
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  13. Tetsuhiro Owaki MD, PhD
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  14. Sumiya Ishigami MD, PhD
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  15. Shoji Natsugoe MD, PhD
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Corresponding author

Correspondence to Hiroshi Okumura MD.

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Desaki, R., Sawada, G., Okumura, H. et al. As a Novel Prognostic Marker, Cysteine/histidine-rich 1 (CYHR1) is a Therapeutic Target in Patients with Esophageal Squamous Cell Carcinoma. Ann Surg Oncol 24, 586–593 (2017). https://doi.org/10.1245/s10434-015-5031-0

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  • DOI: https://doi.org/10.1245/s10434-015-5031-0

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