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大腸癌の罹患率は依然高いが，早期癌の発見率も増加し，主にピットパターンなど腫瘍の表面性状から得る深達度の診断能も向上したことで内視鏡的粘膜切除術(Endoscopic mucosal resection：EMR)や腹腔鏡下手術は急速に拡大してきている．大腸癌におけるリンパ節転移は予後規定因子として重要であり治療方針決定においても重要な因子となるが，リンパ節転移の評価に広く用いられているcomput...ed tomography (CT)，magnetic resonance imaging (MRI)のリンパ節転移検出の感度は決して高くない．術前病期分類を正確に判定する上で，リンパ節転移を含む遠隔転移を予測する高精度の指標が求められている．今回，大腸癌157例の遺伝子プロファイルからリンパ節転移を予測するマーカー遺伝子の検索を行った．遺伝子を同定する上で，その発現異常がゲノムコピー数異常に起因し，安定した発現解析が可能な遺伝子をターゲットとし，解析により同定されたマーカー遺伝子のリンパ節転移との関連と臨床的意義を検討した．
Introduction : Currently, Endoscopic mucosal resection (EMR) and laparoscopic surgery with colorectal cancer (CRC) and has been expanding rapidly. In handling of colon cancer, adaptation of EMR is determined by the depth of tumor invasion. It is important to identify genes to predict lymph node metastasis in early CRC tumors precisely in a reproducible fashion to determine the adaptation of EMR treatment. We performed the comprehensive analysis of gene expression and genomic copy number simultaneously in CRC primary tumors to identify the bona-fide indicator of lymph node metastasis. Materials and Methods : We collected cancer cells specifically by Laser Microdissection (LMD) on 157 cases of primary colorectal cancer, and performed oligo microarrays for gene expression (GE) and aCGH for copy number aberration. As for candidate genes to be associated with lymph node metastasis, we examined reprodicibility by quantitative RT-PCR using cDNA created from the RNA extracted from 172 cases of CRC. Results : As for the association of lymph node metastasis, we found that 240 genes and 54 genes by aCGH and by oligo GE microarray, respectively. According to database of those two arrays, 501 genes were significantly correlated (correlation coefficient > 0.7) with each other, and we found that 11 out of 501 genes were identified as lymph node metastasis related genes with copy number alteration. Of these 11 genes, we focused on PCM1, MTUS1, ASAH1 on 8p22. Then, we confirmed that the decreased expression and genomic deletion of MTUS1 were observed in lymph node positive cases (p = 0.0195) in another subset of 172 cases of CRC. Conclusions : To measure the expression of MTUS1 of the tumor by PCR, we can predict the presence of lymph node metastasis. We expected that the loss of MTUS1 should be an important marker in determining the adaptation of endoscopic resection.続きを見る
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