M65

Purpose: Paclitaxel is an effective treatment for some of the non-small-cell lung cancer (NSCLC) patients. However, prediction of the outcome of paclitaxel treatment at the early stage of the chemotherapy is difficult. M30 and M65 are circulating fragments of cytokeratin 18 released during apoptosis or necrosis, respectively, and have been used as markers to evaluate chemotherapy in some cancers. Here, we aimed to examine M30 and M65 values for predicting the therapeutic outcome of paclitaxel treatment of NSCLC. Methods: The serum levels of M30 and M65 before and after paclitaxel treatment in advance-stage NSCLC patients were analyzed, and compared to those in healthy controls. The importance of the M30 and M65 levels to the outcome of chemotherapy was analyzed. Result: We found that the serum M30 and M65 levels were higher in patients with NSCLC (n = 44) than in control healthy subjects (n = 56) (p < 0.001). Two days after paclitaxel treatment, the serum levels of both M30 and M65 significantly increased in NSCLC patients (p < 0.001). Neither marker alone significantly correlated with overall patient survival, but the ratio of M30 vs M65 appeared to be an important prognostic factor for the overall survival of the patients (p < 0.01). Conclusion: Our results suggest that the serum M30/M65 ratio may be a prognostic factor for the outcome of paclitaxel treatment in NSCLC.

Background: Underage drinking is associated with health risk behaviors. Serum keratin-18 (CK18) levels are increased in liver diseases and may be biomarkers of outcome. The purpose of this study was to determine if the total CK18 (M65) or caspase-cleaved CK18 (M30) levels were different in adolescents admitted to hospital because of alcohol intoxication and controls with excluded liver diseases. Methods: A prospective study included 57 adolescents after alcohol use and 23 control subjects. The concentrations of M30 and M65 in the serum samples were evaluated using an enzyme-linked immunosorbent assay. Results: The median age was 15 (14-17) years and 49% were male. There were significant differences in M65 levels between the study and control groups (p = 0.03). The concentrations of M30 and M65 were insignificant in adolescents divided into subgroups according to blood alcohol concentrations (BAC). Significant positive correlations were found between BAC and M65 levels (p = 0.038; r = 0.3). In receiver operating characteristic (ROC) analysis M65 (cut-off = 125.966 IU/l, Se = 70.2%, Sp = 43.5%) allowed to differentiate between patients with and without alcohol intoxication (AUC = 0.66, p = 0.03). Conclusion: M65 appears to be a promising non-invasive biomarker of hepatocyte injury during alcohol intoxication in adolescents. Moreover, a higher concentration of M65 may indicate early organ injury before the increase in the activity of liver enzymes, alanine aminotransferase (ALT) and aspartate aminotransferase (AST).

Introduction/background: Effective cancer biomarkers for early detection, prognosis, or therapy response prediction are urgently need in metastatic RCC. M30 and M65 are released during apoptotic cell death and precisely reflect epithelial tumor cell death. The aim of this study was to determine the prognostic value of plasma M30 and M65 levels in predicting survival rates for patients with metastatic RCC. Patients and methods: Thirty-nine patients with metastatic RCC and 39 healthy control subjects were included in this study. Serum M30 and M65 levels were measured by ELISA. Results: The median ages of the patients and control subjects were 60 and 58 years, respectively. No difference was detected in the median serum M30 level between the patients and control subjects (53.7 vs. 49.1 U/L; P = .31). The median serum M65 level was significantly higher in patients than in control subjects (334.0 vs. 179.1 U/L; P < .001). Receiver operating characteristic analysis revealed that the best cutoff value for serum M65 level for predicting progression-free survival (PFS) was 313.6 U/L. The median PFS of patients whose M65 levels were ≤ 313.6 U/L was better than that of patients whose M65 levels were > 313.6 U/L (P = .03). Conclusion: To the best of our knowledge, this is the first study to evaluate serum M30 and M65 levels in patients with RCC. Serum M65 levels were significantly elevated in patients with metastatic RCC compared with healthy individuals. In addition, the serum M65 level could be predictive of PFS in patients with RCC.