title: A novel role of serum cytochrome c as a tumor marker in patients with operable cancer.
abstract: OBJECTIVE
  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; P = 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 (P = 0.0004), metastasis (P = 0.0262) except for regional lymph node metastasis, and activity of serum LD (P < 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).
  
  
  CONCLUSIONS
  Serum cyto-c is a potent tumor marker as a predictor for malignant potential in cancers.
authors.affiliation: Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, Nagasaki, 852-8501, Japan.
authors.forename: Akemi
authors.initials: A
authors.lastname: Osaka
authors.forename: Hiroo
authors.initials: H
authors.lastname: Hasegawa
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Yamada
authors.forename: Katsunori
authors.initials: K
authors.lastname: Yanagihara
authors.forename: Tomayoshi
authors.initials: T
authors.lastname: Hayashi
authors.forename: Mariko
authors.initials: M
authors.lastname: Mine
authors.forename: Muneo
authors.initials: M
authors.lastname: Aoyama
authors.forename: Takashi
authors.initials: T
authors.lastname: Sawada
authors.forename: Shimeru
authors.initials: S
authors.lastname: Kamihira
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood; D002272:Carcinoembryonic Antigen / Q000097:blood; D045304:Cytochromes c / Q000097:blood*; D018450:Disease Progression; D005260:Female; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000097:blood* / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D011237:Predictive Value of Tests; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen; D045304:Cytochromes c