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

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


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.


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).


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

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Conflict of interest statement

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

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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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  • Cytochrome c
  • Prediction
  • Tumor marker
  • Metastatic potential