Promoter methylation of the RGC32 gene in nonsmall cell lung cancer.
BACKGROUND
Lung cancer is the leading cause of cancer-related deaths worldwide. Epigenetic inactivation of certain genes by aberrant promoter methylation is recognized as a crucial component in the initiation and progression of lung cancer. Response gene to complement 32 (RGC32) has been identified as a cell cycle regulator induced by activation of complements; however, its role in carcinogenesis is still controversial.


METHODS
The authors examined the methylation status in the promoter region of RGC32 gene in nonsmall cell lung cancers (NSCLCs) using a methylation-specific PCR and correlated the results with clinicopathological features.


RESULTS
RGC32 methylation was found in 45 of 173 NSCLCs (26.0%) and was related to the gene expression. RGC32 methylation was more frequent in females than in males (P<0.05). RGC32 methylation was not significantly associated with the prognosis of patients; however, when the patients were categorized by TP53 mutational status, the effect of RGC32 methylation on prognosis was significantly different between those with and without TP53 mutations (P = .005 [test for homogeneity]). Specifically, RGC32 methylation was associated with significantly worse survival in the cases with wild-type TP53, whereas it exhibited a better survival outcome in the cases with TP53 mutations.


CONCLUSIONS
The current findings suggest that methylation-associated down-regulation of RGC32 plays an important role in the pathogenesis of NSCLC, particularly in females. However, further studies with a large number of cases are needed to confirm the authors' findings.
Kim
Dong Sun
DS
Department of Anatomy, School of Medicine, Kyungpook National University, Daegu 702-422, Republic of Korea.
Lee
Ji Yun
JY
Lee
Su Man
SM
Choi
Jin Eun
JE
Cho
Sukki
S
Park
Jae Yong
JY
D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality; D018797:Cell Cycle Proteins / Q000235:genetics*; D019175:DNA Methylation; D015536:Down-Regulation; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D011401:Promoter Regions, Genetic
D018797:Cell Cycle Proteins; D009124:Muscle Proteins; D009419:Nerve Tissue Proteins; C115049:RGCC protein, human