2006 Fiscal Year Final Research Report Summary
Clinicopathyological and molecular studies for arising and development of lung Adenocarcinoma
| Project/Area Number |
17590305
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Human pathology
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| Research Institution | Kyushu University |
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Principal Investigator |
KOGA Takaomi Kyushu University, Hospital, 講師 (70380615)
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| Co-Investigator(Kenkyū-buntansha) |
YONEMITSU Yoshikazu Kyushu University, Graduate School of Medical Sciences, Division of Pathophysiological and Experimental Pathology, Professor (40315065)
YONEMITSU Yoshikazu Kyushu University, Graduate School of Medical Sciences, Division of Pathophysiological and Experimental Pathology, Professor (40315065)
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| Project Period (FY) |
2005 – 2006
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| Keywords | Non-small cell lung cancer / AAH / BAC / CHFR / smoking / Aurora-A |
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| Research Abstract |
Loss of tumor suppressors and activation of oncogenes lead to carcinogenesis. Abnormal expressions of CHFR, a novel checkpoint gene, or of Aurora kinases, key regulators of mitosis, have 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 non-small-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 with promoter methylation of 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 expression of CHFR was associated with smoking-related squamous cell carcinoma cases and poor prognosis, significantly. Multivariate analysis revealed that CHFR expression was an independent prognostic factor. A statistical correlation was evident between CHFR protein and mRNA expressions.
In conclusion, our results suggest the aberrant expression of Aurora-A and/or of CHFR contributed to the increase in malignant potential in 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.
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