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S100B Protein Expressions as an Independent Predictor of Early Relapse in UICC Stages II and III Colon Cancer Patients after Curative Resection

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

Abstract

Background

S100 calcium-binding proteins such as S100B are elevated in primary malignant melanoma and are used as tumor markers for malignant melanoma and numerous other cancers. The purpose of this study was to identify the novel predictors of early relapse in UICC stages II and III colon cancer patients and thus to identify a subgroup of patients who are at high risk for postoperative early relapse.

Methods

Clinicopathological factors and S100B expression by immunohistochemical staining were retrospectively analyzed in 357 postoperative UICC stages II and III colon cancer patients to determine the predictors of early relapse.

Results

Of 357 patients, 114 patients developed postoperative relapse during the follow-up period. Among 114 relapsed colon cancer patients, postoperative early relapse and non-early relapse were found in 56 patients (49.1%) and 58 patients (50.9%), respectively. Multivariate Cox proportional hazards analysis revealed that the presence of vascular invasion (P = .025; hazard ratio [HR], 5.532; 95% confidence interval [95% CI], 1.985–14.729), high postoperative CEA levels (P = .019; HR, 6.845; 95% CI, 2.393–15.256), and S100B overexpression (P < .001; HR, 26.250; 95% CI, 7.463–96.804) were demonstrated to be independent predictors of postoperative early relapse. Furthermore, postoperative relapsed colon cancer patients with S100B overexpression were demonstrated to have significantly lower overall survival rates than those without S100B overexpression (P < .001).

Conclusions

This study suggests that S100B protein expression is a crucial predictor of early relapse in UICC stages II and III postoperative colon cancer patients and thus could help to define patients with this tumor entity who would benefit from enhanced follow-up and therapeutic program(s).

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References

  1. Arkenau HT, Chua YJ, Cunningham D. Current treatment strategies in elderly patients with metastatic colorectal cancer. Clin Colorectal Cancer. 2007;6:508–15.

    Article  CAS  PubMed  Google Scholar 

  2. Neal CP, Garcea G, Doucas H, Manson MM, Sutton CD, Dennison AR, et al. Molecular prognostic markers in resectable colorectal liver metastases: a systematic review. Eur J Cancer. 2006;42:1728–43.

    Article  CAS  PubMed  Google Scholar 

  3. Korner H, Soreide K, Stokkeland PJ, Soreide JA. Systematic follow-up after curative surgery for colorectal cancer in Norway: a population-based audit of effectiveness, costs, and compliance. J Gastrointest Surg. 2005;9:320–8.

    Article  PubMed  Google Scholar 

  4. Walter EL, Frank EJ. The preoperative assessment and postoperative surveillance of patients with colon and rectal cancer. Surg Clin N Am. 2002;82:1091–108.

    Article  Google Scholar 

  5. Kobayashi H, Mochizuki H, Sugihara K, Morita T, Kotake K, Teramoto T, et al. Characteristics of recurrence and surveillance tools after curative resection for colorectal cancer: a multicenter study. Surgery. 2007;141:67–75.

    Article  PubMed  Google Scholar 

  6. Ahmed FE. Molecular markers that predict response to colon cancer therapy. Expert Rev Mol Diagn. 2005;5:353–5.

    Article  CAS  PubMed  Google Scholar 

  7. Donato R. Intracellular and extracellular roles of S100 proteins. Microsc Res Tech. 2003;60:540–51.

    Article  CAS  PubMed  Google Scholar 

  8. van Dieck J, Fernandez-Fernandez MR, Veprintsev DB, et al. Modulation of the oligomerization state of p53 by differential binding of proteins of the S100family to p53 monomers and tetramers. J Biol Chem. 2009;284:13804–11.

    Article  PubMed  Google Scholar 

  9. Fernandez-Fernandez MR, Veprintsev DB, Fersht AR. Proteins of the S100 family regulate the oligomerization of p53 tumor suppressor. Proc Natl Acad Sci USA. 2005;102:4735–40.

    Article  CAS  PubMed  Google Scholar 

  10. Garrett SC, Varney KM, Weber DJ, Bresnick AR. S100A4, a mediator of metastasis. J Biol Chem. 2006;281:677–80.

    Article  CAS  PubMed  Google Scholar 

  11. Wang G, Wang X, Wang S, Song H, Sun H, Yuan W, et al. Colorectal cancer progression correlates with upregulation of S100A11 expression in tumor tissues. Int J Colorectal Dis. 2008;23:675–82.

    Article  PubMed  Google Scholar 

  12. Garbe C, Leiter U, Ellwanger U, Blaheta HJ, Meier F, Rassner G, et al. Diagnostic value and prognostic significance of protein S-100beta, melanoma-inhibitory activity, and tyrosinase/MART-1 reverse transcription-polymerase chain reaction in the follow-up of high-risk melanoma patients. Cancer. 2003;97:1737–45.

    Article  CAS  PubMed  Google Scholar 

  13. Egberts F, Hitschler WN, Weichenthal M, Hauschild A. Prospective monitoring of adjuvant treatment in high-risk melanoma patients: lactate dehydrogenase and protein S-100B as indicators of relapse. Melanoma Res. 2009;19:31–5.

    Article  CAS  PubMed  Google Scholar 

  14. Wang JY, Yeh CS, Tzou WS, Hsieh JS, Chen FM, Lu CY, et al. Analysis of progressively overexpressed genes in tumorigenesis of colorectal cancers using cDNA microarray. Oncol Rep. 2005;14:65–72.

    PubMed  Google Scholar 

  15. Huang MY, Fang WY, Lee SC, Cheng TL, Wang JY, Lin SR. ERCC2 2251A>C genetic polymorphism was highly correlated with early relapse in high-risk stage II and stage III colorectal cancer patients. BMC Cancer. 2008;8:50–62.

    Article  PubMed  Google Scholar 

  16. Tsai HL, Chu KS, Huang YH, Su YC, Wu JY, Kuo CH, et al. Predictive factors of early relapse in UICC stage I-III colorectal cancer patients after curative resection. J Surg Oncol. 2009;100:736–43.

    Article  PubMed  Google Scholar 

  17. Xie R, Schlumbrecht MP, Shipley GL, Xie S, Bassett RL Jr, Broaddus RR. S100A4 mediates endometrial cancer invasion and is a target of TGF-beta1 signaling. Lab Invest. 2009;89:937–47.

    Article  CAS  PubMed  Google Scholar 

  18. Gongoll S, Peters G, Mengel M, Piso P, Piso P, Klempnauer J, Kreipe H, et al. Prognostic significance of calcium-binding protein S100A4 in colorectal cancer. Gastroenterology. 2002;123:1478–84.

    Article  CAS  PubMed  Google Scholar 

  19. Hemandas AK, Salto-Tellez M, Maricar SH, Leong AF, Leow CK. Metastasis-associated protein S100A4—a potential prognostic marker for colorectal cancer. J Surg Oncol. 2006;93:498–503.

    Article  CAS  PubMed  Google Scholar 

  20. Kim JH, Kim CN, Kim SY, Lee JS, Cho D, Kim JW, et al. Enhanced S100A4 protein expression is clinicopathologically significant to metastatic potential and p53 dysfunction in colorectal cancer. Oncol Rep. 2009;22:41–7.

    CAS  PubMed  Google Scholar 

  21. Lin J, Yang Q, Yan Z, Markowitz J, Wilder PT, Carrier F, et al. Inhibiting S100B restores p53 levels in primary malignant melanoma cancer cells. J Biol Chem, 2004;279:34071–7.

    Article  CAS  PubMed  Google Scholar 

  22. Takashi M, Sakata T, Nakano Y, Yamada Y, Miyake K, Kato K. Elevated concentrations of the beta-subunit of S100 protein in renal cell tumors in rats. Urol Res. 1994;22:251–5.

    Article  CAS  PubMed  Google Scholar 

  23. Suzushima H, Asou N, Hattori T, Takatsuki K. Adult T-cell leukemia derived from S100-beta positive double-negative (CD4-CD8-) T cells. Leuk Lymphoma. 1994;13:257–62.

    Article  CAS  PubMed  Google Scholar 

  24. Hancq S, Salmon I, Brotchi J, Gabius HJ, Heizmann CW, Kiss R, et al. Detection of S100B, S100A6 and galectin-3 ligands in meningiomas as markers of aggressiveness. Int J Oncol. 2004;25:1233–40.

    CAS  PubMed  Google Scholar 

  25. Wilder PT, Rustandi RR, Drohat AC, Weber DJ. S-100B (beta) inhibits the protein kinase C-dependent phosphorylation of a peptide derived from p53 in a Ca2+-dependent manner. Protein Sci. 1998;7:794–8.

    Article  CAS  PubMed  Google Scholar 

  26. Lin J, Blake M, Tang C, Zimmer D, Zimmer D, Rustandi RR, Weber DJ, et al. Inhibition of p53 transcriptional activity by the S100B calcium-binding protein. J Biol Chem. 2001;276:35037–41.

    Article  CAS  PubMed  Google Scholar 

  27. Fearon ER, Vogelstein B. A genetic model for colorectal tumorigenesis. Cell. 1990;61:759–67.

    Article  CAS  PubMed  Google Scholar 

  28. Harpio R, Einarsson R. S100 proteins as cancer biomarkers with focus on S100B in malignant melanoma. Clin Biochem. 2004;37:512–8.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgment

This work was supported by grants from the Kaohsiung Medical University Hospital (KMUH98-8I04), and by Excellence for Cancer Research Center Grant (DOH99-TD-C-111-002) through the funding by Department of Health, Executive Yuan.

Author information

Authors and Affiliations

  1. Department of Biochemistry, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

    Chi-Ching Hwang PhD & Hsin-Wei Chen PhD

  2. Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital—Kaohsiung Medical Center, College of Medicine, Chang Gung University, Kaohsiung, Taiwan

    Han-Tan Chai PhD

  3. Department of Emergency Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan

    Hsiang-Lin Tsai MD

  4. Program of Bachelor of Health Beauty, School of Medical and Health Sciences, Fooyin University, Kaohsiung, Taiwan

    Hsiang-Lin Tsai MD

  5. Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

    Chien-Yu Lu MD & Fang-Jung Yu MD

  6. Department of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

    Chien-Yu Lu MD

  7. Department of Radiation Oncology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

    Ming-Yii Huang MD

  8. Department of Radiation Oncology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

    Ming-Yii Huang MD

  9. Cancer Center and Division of Gastrointestinal and General Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

    Jaw-Yuan Wang MD, PhD

  10. Department of Surgery, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

    Jaw-Yuan Wang MD, PhD

  11. Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

    Jaw-Yuan Wang MD, PhD

  12. Department of Medical Genetics, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

    Jaw-Yuan Wang MD, PhD

Authors
  1. Chi-Ching Hwang PhD
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  2. Han-Tan Chai PhD
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  3. Hsin-Wei Chen PhD
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  4. Hsiang-Lin Tsai MD
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  5. Chien-Yu Lu MD
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  6. Fang-Jung Yu MD
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  7. Ming-Yii Huang MD
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  8. Jaw-Yuan Wang MD, PhD
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Corresponding author

Correspondence to Jaw-Yuan Wang MD, PhD.

Additional information

Chi-Ching Hwang and Han-Tan Chai contributed equally to the study.

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Hwang, CC., Chai, HT., Chen, HW. et al. S100B Protein Expressions as an Independent Predictor of Early Relapse in UICC Stages II and III Colon Cancer Patients after Curative Resection. Ann Surg Oncol 18, 139–145 (2011). https://doi.org/10.1245/s10434-010-1209-7

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  • DOI: https://doi.org/10.1245/s10434-010-1209-7

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