title: Usefulness of monitoring the circulating Krebs von den Lungen-6 levels to predict the clinical outcome of patients with advanced nonsmall cell lung cancer treated with epidermal growth factor receptor tyrosine kinase inhibitors.
abstract: Krebs von den Lungen-6 (KL-6) is a high molecular weight glycoprotein classified in the category of human MUC1 mucin. KL-6 has been reported to serve as a sensitive marker for interstitial pneumonia; however, recent studies have suggested that it can also be used as a tumor marker as its origin shows. To further elucidate the clinicopathological significance of circulating KL-6 in lung cancer, we monitored the circulating KL-6 levels in advanced nonsmall cell lung cancer (NSCLC) patients and analyzed the association between these levels and the clinical outcome of EGFR-TKI treatment. The pretreatment levels of circulating KL-6 were found to be significantly higher in progressive disease (PD) patients than disease-controlled (partial response (PR) and stable disease (SD)) patients. Multivariate analyses revealed the circulating KL-6 level to be an independent prognostic factor for overall survival as well as progression-free survival. In addition to these observations, we found that changes in circulating KL-6 levels at 2 weeks after the start of EGFR-TKI treatment from the baseline could quite precisely discriminate PD cases from PR or SD patients and the clinical outcome of EGFR-TKI in NSCLC patients. These results indicate that the monitoring of circulating KL-6 levels in NSCLC patients is effective for both selecting patients to be treated with EGFR-TKI and predicting the clinical outcome of EGFR-TKI. In addition, the findings suggest that the circulating KL-6 level could be used as a clinically relevant biomarker in patients with NSCLC, particularly those who are candidates for EGFR-TKI treatment.
authors.affiliation: Department of Molecular and Internal Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Nobuhisa
authors.initials: N
authors.lastname: Ishikawa
authors.forename: Noboru
authors.initials: N
authors.lastname: Hattori
authors.forename: Akihoto
authors.initials: A
authors.lastname: Yokoyama
authors.forename: Sonosuke
authors.initials: S
authors.lastname: Tanaka
authors.forename: Ryohei
authors.initials: R
authors.lastname: Nishino
authors.forename: Koji
authors.initials: K
authors.lastname: Yoshioka
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Ohshimo
authors.forename: Kazunori
authors.initials: K
authors.lastname: Fujitaka
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ohnishi
authors.forename: Hironobu
authors.initials: H
authors.lastname: Hamada
authors.forename: Koji
authors.initials: K
authors.lastname: Arihiro
authors.forename: Nobuoki
authors.initials: N
authors.lastname: Kohno
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000097:blood; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood*; D002272:Carcinoembryonic Antigen / Q000097:blood; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D018450:Disease Progression; D018572:Disease-Free Survival; D004563:Electrochemistry; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics; D005260:Female; D006801:Humans; D053539:Keratin-19; D007633:Keratins / Q000097:blood; D008163:Luminescent Measurements; D008175:Lung Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D018396:Mucin-1 / Q000097:blood*; D009154:Mutation; D016017:Odds Ratio; D018579:Patient Selection; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D016896:Treatment Outcome
chemical_list: D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen; D053539:Keratin-19; C060192:MUC1 protein, human; D018396:Mucin-1; D047428:Protein Kinase Inhibitors; C102012:antigen CYFRA21.1; D007633:Keratins; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases