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

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

Elevation of Serum KL-6 Glycoprotein or Surfactant Protein-D in Adult T-cell Leukemia with Distinct Pulmonary Complications

Patients with hematological malignancies frequently suffer from lung diseases as a complication. However, it is difficult to discriminate leukemic invasion into the lung from infectious pulmonary complications. The serum level of Krebs von den Lungen-6 (KL-6), which is a mucin-like glycoprotein, is increased in more than 70% of patients with interstitial pneumonia. Surfactant protein-D (SP-D) is produced mainly in the lung by alveolar type II and bronchiolar epithelial cells and is a useful serum marker for interstitial pneumonia. We therefore measured the levels of KL-6 and SP-D in sera from 128 patients (76 males and 52 females, mean age: 59 years) with hematological malignancies, including adult T-cell leukemia (ATL). Overall, the increase in KL-6 or SP-D, above each cut-off value (500 U/ml for KL-6 and 110 ng/ml for SP-D), was detected in 11 patients (8.6%) or 10 patients (7.8%), respectively. In contrast, among 67 ATL patients, 15 patients had high serum levels of KL-6 and/or SP-D; both were elevatedin 2 patients, only KL-6 was elevated in 6 patients and only SP-D was elevated in 7 patients. Thus, serum KL-6 and SP-D appear to be elevated in a mutually exclusive manner in ATL. Indeed, high serum levels of KL-6 were closely related to the stage of ATL, while the serum SP-D was elevated in ATL patients with pulmonary infection. In conclusion, the combined measurement of KL-6 and SP-D in ATL may become a useful means to discriminate leukemic pulmonary lesions from infectious pulmonary complications