title: Importin subunit alpha-2 is identified as a potential biomarker for non-small cell lung cancer by integration of the cancer cell secretome and tissue transcriptome.
abstract: The cancer cell secretome may contain potentially useful biomarkers. In this study, we integrated the profiles of secreted proteins in lung cancer cell lines with mRNA expression levels from pulmonary adenocarcinoma tissue, with a view to identify effective biomarkers for non-small cell lung cancer (NSCLC). Among the novel candidates isolated, importin subunit alpha-2 (also known as karyopherin subunit alpha [KPNA]-2), was selected for further validation. Immunohistochemical staining revealed overexpression of KPNA2 in the nuclei of tumor cells, compared with adjacent normal cells. A sandwich ELISA assay developed to detect KPNA2 levels in serum samples showed significantly higher serum KPNA2 in NSCLC patients than in healthy controls. A combination of serum KPNA2 and carcinoembryonic antigen displayed higher diagnostic capacity than either marker alone. Importantly, protein levels of KPNA2 in pleural effusion from NSCLC patients were also significantly higher than those from non-lung cancer. Moreover, knockdown of KPNA2 inhibited the migration ability and viability of lung cancer cells. Our results collectively suggest that integration of the cancer cell secretome and transcriptome datasets provides an efficient means of identifying novel biomarkers for NSCLC, such as KPNA2.
authors.affiliation: Graduate Institute of Biomedical Sciences, Chang Gung University, Tao-Yuan, Taiwan.
authors.forename: Chun-I
authors.initials: CI
authors.lastname: Wang
authors.forename: Chih-Liang
authors.initials: CL
authors.lastname: Wang
authors.forename: Chih-Wei
authors.initials: CW
authors.lastname: Wang
authors.forename: Chi-De
authors.initials: CD
authors.lastname: Chen
authors.forename: Chih-Ching
authors.initials: CC
authors.lastname: Wu
authors.forename: Ying
authors.initials: Y
authors.lastname: Liang
authors.forename: Ying-Huang
authors.initials: YH
authors.lastname: Tsai
authors.forename: Yu-Sun
authors.initials: YS
authors.lastname: Chang
authors.forename: Jau-Song
authors.initials: JS
authors.lastname: Yu
authors.forename: Chia-Jung
authors.initials: CJ
authors.lastname: Yu
mesh_terms: D000368:Aged; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000097:blood* / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood* / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000097:blood* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010996:Pleural Effusion / Q000378:metabolism; D034741:RNA, Small Interfering; D028901:alpha Karyopherins / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C490630:KPNA2 protein, human; D034741:RNA, Small Interfering; D028901:alpha Karyopherins