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A novel role of serum cytochrome c as a tumor marker in patients with operable cancer

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Abstract

Purpose

This study aimed to evaluate serum cytochrome c (cyto-c) levels as a novel role of tumor marker in patients with operable malignant tumors.

Methods

Serum cyto-c levels and lactate dehydrogenase (LD) activity were measured in a total of 257 cases (232 malignant and 25 benign). To identify the relationship between serum cyto-c and current tumor markers, six variables, such as gender, age, invasion, lymph node metastasis, distant metastasis, and LD, were analyzed by uni- and multivariate regression analysis methods. The test performance of serum cyto-c for the prediction of malignant behavior was evaluated by receiver operating characteristic (ROC) curves.

Results

The serum cyto-c level was significantly higher in patients with malignant tumors than patients with benign tumors (20.6 vs. 15.5 ng/mL; = 0.017, Mann–Whitney U test). No difference in the levels among subtypes of cancer was found, indicating that the change in serum cyto-c levels reflect cancer individually and not specific subtypes of cancer. The survival in patients with serum cyto-c levels over 40 ng/mL was poor (Kaplan–Meier test, P < 0.0001, Hazard ratio 16.76, 95% confidential interval 4.45–63.04). Multiple linear regression analyses disclosed the close association of serum cyto-c levels with invasion (= 0.0004), metastasis (= 0.0262) except for regional lymph node metastasis, and activity of serum LD (< 0.0001), all of which are well known to represent malignant behavior. Conversely, the measurement of serum cyto-c was verified to have excellent diagnostic accuracy of 0.802 and 0.781 for the detection of invasion and metastasis (the area under curves of the constructed ROCs).

Conclusion

Serum cyto-c is a potent tumor marker as a predictor for malignant potential in cancers.

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References

  1. Adachi N, Hirota M, Hamaguchi M, Okamoto K, Watanabe K, Endo F (2004) Serum cytochrome c level as a prognostic indicator in patients with systemic inflammatory response syndrome. Clin Chim Acta 342:127–136

  2. Alleyne T, Joseph J, Sampson V (2001) Cytochrome-c detection: a diagnostic marker for myocardial infarction. Appl Biochem Biotechnol 90:97–105

  3. Barczyk K, Kreuter M, Pryjma J, Booy EP, Maddika S, Ghavami S, Berdel WE, Roth J, Los M (2005) Serum cytochrome c indicates in vivo apoptosis and can serve as a prognostic marker during cancer therapy. Int J Cancer 20:167–173

  4. Beachy SH, Repasky EA (2008) Using extracellular biomarkers for monitoring efficacy of therapeutics in cancer patients: an update. Cancer Immunol Immunother 57:759–775

  5. Harris AL (2002) Hypoxia–a key regulatory factor in tumour growth. Nat Rev Cancer 2:38–47

  6. Holdenrieder S, Stieber P (2004) Apoptotic markers in cancer. Clin Biochem 37:605–617

  7. Hosoya M, Nunoi H, Aoyama M, Kawasaki Y, Suzuki H (2005) Cytochrome c and tumor necrosis factor-alpha values in serum and cerebrospinal fluid of patients with influenza-associated encephalopathy. Pediatr Infect Dis J. 24:467–470

  8. Hosoya M, Kawasaki Y, Katayose M, Sakuma H, Watanabe M, Igarashi E, Aoyama M, Nunoi H, Suzuki H (2006) Prognostic predictive values of serum cytochrome c, cytokines, and other laboratory measurements in acute encephalopathy with multiple organ failure. Arch Dis Child 91:469–472

  9. Manjo G, Joris I (1995) Apoptosis, oncosis, and necrosis. An overview of cell death. Amer J Pathol 146:3–15

  10. Meggiato T, Calabrese F, Valente M, Favaretto E, Baliello E, Del Favero G (2000) Spontaneous apoptosis and proliferation in human pancreatic csancer. Pancreas 20:117–122

  11. Osaka A, Hasegawa H, Tsuruda K, Inokuchi N, Yanagihara K, Yamada Y, Aoyama M, Sawada T, Kamihira S (2008) Serum cytochrome c to indicate the extent of ongoing tumor cell death. Int J Lab Hematol (Epub ahead of print)

  12. Tanaka F, Otake Y, Yanagihara K, Kawano Y, Miyahara R, Li M, Ishikawa S, Wada H (2003) Correlation between apoptotic index and angiogenesis in non-small cell lung cancer: comparison between CD105 and CD34 as a marker of angiogenesis. Lung Cancer 39:289–296

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Conflict of interest statement

None of the authors have any conflicts of interest in connection with this work.

Author information

Correspondence to Shimeru Kamihira.

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Osaka, A., Hasegawa, H., Yamada, Y. et al. A novel role of serum cytochrome c as a tumor marker in patients with operable cancer. J Cancer Res Clin Oncol 135, 371–377 (2009). https://doi.org/10.1007/s00432-008-0479-y

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Keywords

  • Cytochrome c
  • Prediction
  • Tumor marker
  • Metastatic potential