Department of Anatomy, School of Medicine, Kyungpook National University, Daegu 702-422, Republic of Korea.
Cancer. 2011 Feb 1;117(3):590-6. doi: 10.1002/cncr.25451. Epub 2010 Sep 22.
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.
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.
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.
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.
肺癌是全球癌症相关死亡的主要原因。异常启动子甲基化导致某些基因的表观遗传失活被认为是肺癌发生和发展的重要组成部分。补体反应基因 32（RGC32）已被确定为补体激活诱导的细胞周期调节剂；然而，其在致癌作用中的作用仍存在争议。
作者使用甲基化特异性 PCR 检测非小细胞肺癌（NSCLC）中 RGC32 基因启动子区域的甲基化状态，并将结果与临床病理特征相关联。
在 173 例 NSCLC 中，发现 RGC32 甲基化 45 例（26.0%），与基因表达相关。RGC32 甲基化在女性中比男性更常见（P<0.05）。RGC32 甲基化与患者的预后无显著相关性；然而，当根据 TP53 突变状态对患者进行分类时，RGC32 甲基化对预后的影响在无 TP53 突变和有 TP53 突变的患者之间存在显著差异（P=.005 [检验同质性]）。具体而言，在 TP53 野生型的情况下，RGC32 甲基化与生存率显著降低相关，而在 TP53 突变的情况下，RGC32 甲基化则与生存率显著提高相关。
目前的研究结果表明，RGC32 的甲基化相关下调在 NSCLC 的发病机制中起着重要作用，特别是在女性中。然而，需要更多的大样本量研究来证实作者的发现。
