Serum Heparan Sulfate Concentration is Correlated with the Failure of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Treatment in Patients with Lung Adenocarcinoma
| Autor: | Takashi Sone, Nagahiro Saijo, Kazuo Kasahara, Asao Sakai, Norihiko Ikeda, Hideharu Kimura, Tokuzo Arao, Kazuko Sakai, Atsushi Horiike, Makoto Nishio, Takeharu Yamanaka, Kazuko Matsumoto, Tatsuo Ohira, Fumiaki Koizumi, Kazuto Nishio |
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| Rok vydání: | 2011 |
| Předmět: |
Male
Pulmonary and Respiratory Medicine Lung Neoplasms Heparan sulfate Adenocarcinoma EGFR-tyrosine kinase inhibitors chemistry.chemical_compound Erlotinib Hydrochloride Growth factor receptor Non-small cell lung cancer Carcinoma Non-Small-Cell Lung Antineoplastic Combined Chemotherapy Protocols Biomarkers Tumor Medicine Humans Epidermal growth factor receptor Treatment Failure Protein Kinase Inhibitors Aged Neoplasm Staging Retrospective Studies Performance status biology business.industry Gefitinib medicine.disease ErbB Receptors chemistry Oncology Mutation Cancer research biology.protein Quinazolines Biomarker (medicine) Female Heparitin Sulfate Signal transduction business Progressive disease |
| Zdroj: | Journal of Thoracic Oncology. 6(11):1889-1894 |
| ISSN: | 1556-0864 |
| DOI: | 10.1097/jto.0b013e3182286d41 |
| Popis: | Introduction The epidermal growth factor receptor ( EGFR ) mutation status is a validated biomarker for the stratification of EGFR-tyrosine kinase inhibitor (EGFR-TKIs) treatment in patients with non-small cell lung cancer (NSCLC); however, its use is limited in patients with wild-type EGFR, and new biomarkers are needed. We hypothesized that the serum concentration of heparan sulfate (HS), which activates oncogenic growth factor receptor signaling through EGFR and non-EGFR signaling pathways, may be a novel glycobiological biomarker for EGFR-TKIs treatment in NSCLC. Methods The pretreatment serum HS concentrations were determined using enzyme-linked immunosorbent assay in 83 patients with stage IV non-small cell lung adenocarcinoma who received EGFR-TKIs treatment. The relationship between the serum HS concentrations and patient characteristics, tumor response, progression-free survival (PFS), and overall survival (OS) were analyzed. Results Patient sex, performance status, smoking history, and EGFR mutation status were associated with tumor response. The serum HS concentrations were significantly higher among patients with progressive disease than among those without progressive disease ( p = 0.003). Furthermore, the serum HS concentrations were strongly associated with a poor PFS and OS in a univariate Cox analysis ( p = 0.0022 and p = 0.0003, respectively). A stratified multivariate Cox model according to the EGFR mutation status showed that higher HS concentrations were significantly associated with a shorter PFS and OS ( p = 0.0012 and p = 0.0003). Conclusion We concluded that a high-serum HS concentration was strongly related to a poor treatment outcome of EGFR-TKIs and may be a promising noninvasive and repeatable glycobiological biomarker in cancer treatment. |
| Databáze: | OpenAIRE |
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