CHFR expression is preferentially impaired in smoking‐related squamous cell carcinoma of the lung, and the diminished expression significantly harms outcomes

• Published in: International journal of cancer 2008-10, Vol.123 (7), p.1623-1630
• Main Authors: Takeshita, Masafumi, Koga, Takaomi, Takayama, Koichi, Kouso, Hidenori, Nishimura‐Ikeda, Yuko, Yoshino, Ichiro, Maehara, Yoshihiko, Nakanishi, Yoichi, Sueishi, Katsuo
• Format: Article
• Language: English
• Subjects: Aurora‐A; Base Sequence; Biological and medical sciences; Carcinoma, Squamous Cell - etiology; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - pathology; Cell Cycle Proteins - genetics; checkpoint; CHFR; DNA Methylation; DNA Primers; Female; Humans; Immunohistochemistry; Lung Neoplasms - etiology; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Male; Medical sciences; Neoplasm Proteins - genetics; NSCLC; Poly-ADP-Ribose Binding Proteins; Prognosis; Promoter Regions, Genetic; smoking; Smoking - adverse effects; Tobacco, tobacco smoking; Toxicology; Tumors; Ubiquitin-Protein Ligases
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.23673

Loss of tumor suppressors and activation of oncogenes lead to carcinogenesis. Abnormal expression of CHFR, a novel checkpoint gene, or of Aurora kinases, key regulators of mitosis, has been detected in a variety of solid tumors. Recently, CHFR has been revealed to ensure chromosomal stability by controlling the expression level of Aurora‐A in vitro. However, the frequency of aberrant expression of these proteins and the association with clinicopathologic parameters remain poorly defined in nonsmall‐cell lung cancer (NSCLC). In this study, we investigated the immunohistochemical protein expression of CHFR and Aurora‐A in 157 NSCLC cases and evaluated the association between clinicopathologic parameters statistically. The relationship between CHFR protein and mRNA levels and the association between this relationship and promoter methylation of the CHFR gene were also examined in 20 frozen sections of NSCLC. Overexpression of Aurora‐A and reduced expression of CHFR were found in 94 cases (59.8%) and 62 cases (39%) of NSCLC, respectively, and those were significantly correlated with tumor differentiation and size. Moreover, diminished CHFR expression was significantly associated with smoking‐related squamous cell carcinoma cases and poor prognosis. Multivariate analysis revealed that CHFR expression was an independent prognostic factor. A statistical correlation was evident between CHFR protein and mRNA expression. In conclusion, our results suggest the aberrant expression of Aurora‐A and/or of CHFR contributed to the increase in the malignant potential of NSCLC. We also revealed that CHFR expression was predominantly impaired in smoking‐related squamous cell carcinoma and might be a useful prognostic marker in NSCLC. © 2008 Wiley‐Liss, Inc.