Serum levels of Krebs von den Lungen-6 as a promising marker for predicting occurrence and deterioration of systemic sclerosis-associated interstitial lung disease from a Chinese cohort.

AIM: A prospective and longitudinal study to investigate the correlations between Krebs von den Lungen-6 (KL-6) serum levels and systemic sclerosis associated with interstitial lung disease (SSc-ILD). METHOD: Blood samples of baseline and the time point at 2 years follow-up intervals were collected for the measurement of serum KL-6 levels. The baseline clinical, laboratory characteristics, and incidence density of newly diagnosed ILD during the follow up were compared between SSc patients with elevated serum KL-6 levels (KL-6 > 500 U/mL) and those with normal KL-6 levels (KL-6 ≤ 500 U/mL) at baseline. Further, we explored the association between serum KL-6 and deterioration of ILD measured by lung function parameters during follow-up of 2 years. RESULTS: Patients with elevated baseline serum KL-6 had a significant tendency to have disappearance of the finger pad. The incidence density of new-onset ILD in SSc patients with elevated baseline serum KL-6 and those with normal baseline serum KL-6 was 1.33% and 0.51%, respectively. Among the mild lung injury group, the incidence density of ILD deterioration in SSc patients with elevated baseline serum KL-6 and those with normal serum KL-6 was 1.2% and 0.74%, respectively. CONCLUSION: Serum KL-6 level correlates with the clinical manifestations of microvascular injury. Baseline elevated serum KL-6 may predict deterioration of lung function of SSc-ILD patients with mild lung injury.

Diagnostic value of KL-6 in idiopathic interstitial pneumonia.

BACKGROUND: Idiopathic interstitial pneumonia (IIP) can induce type II alveolar epithelial cell proliferation and pulmonary basement membrane damage and subsequent release of Krebs von den Lungen-6 antigen (KL-6) to the bloodstream. This study investigated the diagnostic and prognostic value of serum KL-6 levels for IIP. METHODS: One hundred five patients with lung disease were divided into IIP (n=75) and non-IIP groups (n=30) according to pathological and computed tomography findings. Serum KL-6 levels were evaluated in blood samples from all subjects. Nineteen IIP group patients were also subjected to a longitudinal study of disease progression and serum KL-6 levels over time. RESULTS: Serum KL-6 levels were significantly higher in the IIP group vs. the non-IIP group [1,096.0 (565.0-1,544.0) vs. 226.0 (173.5-346.5) U/mL; P<0.01]. Within the IIP group, serum KL-6 levels differed significantly between patients with and without concomitant disease or pulmonary infection (Z=-2.475, P=0.013). In a receiver operating characteristic (ROC) curve analysis, the area below the curve for serum KL-6 was 0.911 [95% confidence interval (CI): 0.847-0.975, P<0.001], indicating a good diagnostic performance for IIP, with a cut-off level of 485 U/mL, sensitivity of 85.33%, specificity of 90.00%, positive predictive value (PPV) of 95.52%, negative predictive value (NPV) of 71.05%, and Kappa value of 0.70. Accordingly, the serum KL-6 and clinical diagnostic results were consistent. Moreover, in the longitudinal study, the serum KL-6 levels differed significantly from before to after treatment in patients with exacerbated or improved disease (P=0.004 and P=0.043, respectively), whereas no obvious changes were observed in patients with stable disease (P=0.692). CONCLUSIONS: The serum KL-6 level is a valuable and significant diagnostic marker of IIP and a useful predictor of clinical prognosis.

Prognostic value of serial serum KL-6 measurements in patients with idiopathic pulmonary fibrosis.

BACKGROUND: The prognostic significance of serial measurements of serum KL-6 levels in patients with idiopathic pulmonary fibrosis (IPF) is unclear; hence, it was assessed in this study. METHODS: Medical records of 66 patients with IPF, who were not treated with pirfenidone prior to enrollment, were retrospectively reviewed for information on clinical progress, forced vital capacity (FVC), survival, and serum KL-6 levels. We assessed initial serum levels of KL-6, serial changes in serum KL-6 levels, yearly decline in FVC (ΔFVC), and the rate of decline (%ΔFVC). RESULTS: Patients with increased serum KL-6 levels during follow-up had a significantly steeper decline in ΔFVC than those with no KL-6 increase (-201 vs. -50.7ml/year; p=0.0001). Patients with both initial serum KL-6 ≥1000U/ml and serial increases in serum KL-6 had the steepest decline, while those with both initial serum KL-6 <1000ml and no serial increases in KL-6 had the least decline in ΔFVC and %ΔFVC. Relative to the non-increased KL-6 group, survival in the increased KL-6 group tended to be poorer (p=0.0530). Patients with both initial serum KL-6 values <1000U/ml and no serial increase in KL-6 had more favorable prognoses than those with serial increases in KL-6 or initial serum KL-6 values ≥1000U/ml (p<0.0044). Prognosis was significantly poorer in patients with serial KL-6 changes >51.8U/ml/year than in those with serial KL-6 changes <51.8U/ml/year (p=0.0009). CONCLUSION: Thus, serial serum KL-6 measurements can be useful for assessing prognosis in patients with IPF.

Prognostic significance of preoperative serum Krebs von den Lungen-6 level in non-small cell lung cancer.

OBJECTIVES: We retrospectively analyzed the prognostic significance of preoperative serum Krebs von den Lungen-6 (KL-6) level in non-small cell lung cancer (NSCLC) patients. METHODS: We enrolled 175 NSCLC patients who underwent curative surgery between 2009 and 2011. We subdivided the patients into 2 groups: with and without interstitial lung disease (ILD). Prognostic significance of serum KL-6 level was examined. RESULTS: The 5-year survival of patients with high serum KL-6 level was poor. Multivariate analysis also revealed the prognostic significance of serum KL-6 level. Serum KL-6 level was also a prognostic factor for patients without ILD. Although the number of patients with ILD was small, in patients with ILD, there was a trend towards an association between serum KL-6 level and patients' prognosis but this did not reach statistical significance. CONCLUSIONS: Serum KL-6 level is a prognostic factor for resected NSCLC patients, especially patients without ILD. There is a possibility that serum KL-6 level is a prognostic marker regardless of the presence of ILD.

Serum KL-6 concentrations are associated with molecular sizes and efflux behavior of KL-6/MUC1 in healthy subjects.

BACKGROUND: Serum KL-6, a sialylated sugar chain on human MUC1, is used as a marker of interstitial lung diseases. We recently reported that efflux behavior of KL-6/MUC1 from the alveoli into the bloodstream assessed by molecular analysis differed according to genetically determined molecular sizes and influenced serum KL-6 concentrations in sarcoidosis. This study was designed to investigate associations between molecular size and efflux behavior of KL-6/MUC1, and factors contributing to serum KL-6 concentrations in healthy subjects. METHODS: Western blot analysis using anti-KL-6 antibody was performed on serum obtained from 250 healthy subjects. RESULTS: The efflux behavior of KL-6/MUC1 differed according to the genetically determined molecular sizes in healthy subjects. In subjects having low molecular size, there were significant associations between smoking status, aging, renal function and serum KL-6 concentrations. However, these associations were not significant in the subjects having higher molecular size and the efflux behavior of high molecular size was the only significant determinant of serum KL-6 concentrations. CONCLUSIONS: This study showed an association between KL-6/MUC1 efflux based on molecular size and serum KL-6 concentrations in healthy subjects. We propose that the molecular size and efflux behavior of KL-6/MUC1 should be considered when interpreting serum KL-6 concentrations.

Serum KL-6 in radioactive pneumonia with lung cancer / 国际肿瘤学杂志

Serum KL-6 is a category of glycoprotein coded by the epithelium of sticky protein 1(MUC1) gene,which has already been regarded as an indicator of interstitial lung diseases,and later found highly expressed in part of malignant tumor patients.In recent years,studies has found that serum KL-6 is associated with the incidence of radioactive pneumonia,and monitoring serum KL-6 can predict the occurrence of radioactive pneumonia as well assess the severity and prognosis of disease.