Chondrolectin Is a Novel Diagnostic Biomarker and a Therapeutic Target for Lung Cancer

• Published in: Clinical cancer research Vol. 17; no. 24; pp. 7712 - 7722
• Main Authors: MASUDA, Ken, TAKANO, Atsushi, OSHITA, Hideto, AKIYAMA, Hirohiko, TSUCHIYA, Eiju, KOHNO, Nobuoki, NAKAMURA, Yusuke, DAIGO, Yataro
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15.12.2011
• Subjects: Aged; Animals; Antineoplastic agents; Antitumor agents; Biological and medical sciences; biomarkers; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - metabolism; Carcinoma, Non-Small-Cell Lung - pathology; Cell Line; Cell Line, Tumor; Cell survival; Cercopithecus aethiops; COS Cells; DNA microarrays; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Genetic Predisposition to Disease - genetics; Humans; Immunohistochemistry; Invasiveness; Kaplan-Meier Estimate; Lectins, C-Type - genetics; Lectins, C-Type - metabolism; Lung cancer; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Male; Mammalian cells; Medical sciences; Membrane Proteins - genetics; Membrane Proteins - metabolism; Middle Aged; Multivariate Analysis; Non-small cell lung carcinoma; Oligonucleotide Array Sequence Analysis; Pharmacology. Drug treatments; Pneumology; Prognosis; Reverse Transcriptase Polymerase Chain Reaction; RNA Interference; siRNA; Tissue Array Analysis; Tumors; Tumors of the respiratory system and mediastinum; Lung disease; Treatment; Targeting; Respiratory disease; Targeted therapy; Lung cancer; Biological marker; Bronchus disease; Malignant tumor; Diagnosis; Bronchopulmonary; Cancer
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.ccr-11-0619

This study aims to identify molecules that might be useful as diagnostic/prognostic biomarkers and as targets for the development of new molecular therapies for lung cancer. We screened for genes that were highly transactivated in a large proportion of 120 lung cancers by means of a cDNA microarray representing 27,648 genes and found chondrolectin (CHODL) as a candidate. Tumor tissue microarray was applied to examine the expression of CHODL protein and its clinicopathologic significance in archival non-small cell lung cancer (NSCLC) tissues from 295 patients. A role of CHODL in cancer cell growth and/or survival was examined by siRNA experiments. Cellular invasive effect of CHODL on mammalian cells was examined by Matrigel assays. Immunohistochemical staining revealed that strong positivity of CHODL protein was associated with shorter survival of patients with NSCLC (P = 0.0006), and multivariate analysis confirmed it to be an independent prognostic factor. Treatment of lung cancer cells with siRNAs against CHODL suppressed growth of the cancer cells. Furthermore, induction of exogenous expression of CHODL conferred growth and invasive activity of mammalian cells. CHODL is likely to be a prognostic biomarker in the clinic and targeting CHODL might be a strategy for the development of anticancer drugs.