title: CHFR expression is preferentially impaired in smoking-related squamous cell carcinoma of the lung, and the diminished expression significantly harms outcomes.
abstract: 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.
authors.affiliation: Division of Pathophysiological and Experimental Pathology, Department of Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Takeshita
authors.forename: Takaomi
authors.initials: T
authors.lastname: Koga
authors.forename: Koichi
authors.initials: K
authors.lastname: Takayama
authors.forename: Hidenori
authors.initials: H
authors.lastname: Kouso
authors.forename: Yuko
authors.initials: Y
authors.lastname: Nishimura-Ikeda
authors.forename: Ichiro
authors.initials: I
authors.lastname: Yoshino
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Maehara
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Nakanishi
authors.forename: Katsuo
authors.initials: K
authors.lastname: Sueishi
mesh_terms: D001483:Base Sequence; D002294:Carcinoma, Squamous Cell / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D018797:Cell Cycle Proteins / Q000235:genetics*; D019175:DNA Methylation; D017931:DNA Primers; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics*; D000075223:Poly-ADP-Ribose Binding Proteins; D011379:Prognosis; D011401:Promoter Regions, Genetic; D012907:Smoking / Q000009:adverse effects*; D044767:Ubiquitin-Protein Ligases
chemical_list: D018797:Cell Cycle Proteins; D017931:DNA Primers; D009363:Neoplasm Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; C412002:CHFR protein, human; D044767:Ubiquitin-Protein Ligases