Association between Genomic Alterations and Prognosis of Locally Advanced Colorectal Cancer-A Study by Comparative Genomic Hybridization

以比較性基因體雜交法分析局部侵襲性大腸直腸癌預後和基因體變異間的關係

朱俊合(Jiun-Ho Ju) ； 姜正愷(Jeng-Kai Jiang) ； 陳彥彰(Yann-Jang Chen) ； 林奇宏(Chi-Hung Lin) ； 李芬瑤(Anna Fen-Yan Li) ； 張世慶(Shih-Ching Chang) ； 王煥昇(Huann-Sheng Wang) ； 楊純豪(Shung-Haur Yang) ； 陳維熊(Wei-Shone Chen) ； 林資琛(Tzu-Chen Lin) ； 林楨

《中華民國大腸直腸外科醫學會雜誌》 16卷2期 (2005/06) Pp. 53-60

https://doi.org/10.6312/SCRSTW.2005.16(2).09407

摘要

目的　在台灣大腸直腸癌佔癌症死亡原因的第三位。對於局部侵襲性大腸直腸癌，雖然能將病灶完全切除其預後是很好的，但仍有20-30%的病人其預後和第三期大腸直腸癌是類似的。這篇研究的目的是利用比較性基因體雜交法來找出局部侵襲性大腸直腸癌預後不佳的因子。
方法　從1980年1月到2000年12月，台北榮民總醫院電腦資料中共有177位是局部侵襲性大腸直腸癌(pT4N0M0)病人。其中有5位產生復發，12位因癌症死亡（定義為預後不佳組）。其中有15位病人可取得病理標本。另外再找出15位條件相近卻沒有復發或因為癌症死亡的病人作為對照組（是為預後良好組）。我們以比較性基因體雜交法分析兩組基因體變異的差別。
結果　兩組各有12個標本作出結果。基因體變化的位置在兩組中是差不多的，常見基因重複的位置是在染色體8q，13q，7q，20q上。基因缺損則發生在17P及8P。不過預後不佳這組還是相對上有較多的基因體變化(total CGH events per tumor：4.5±4.9 vs. 3.5±3.1，P=0.56；losses：1.8±2.4 vs. 0.8±0.8，P=0.16)。另外染色體15q的缺損全發生在預後不佳這一組(15q11-q15，q24-q26)，而且當染色體缺損數目大於或等於三個時，預後會不好(p＝0.04)。
結論　局部侵襲性大腸直腸癌病人中預後不佳的有較多的基因缺損，尤其是15q的缺損。15qll-ql5及15q24-q26將是我們進一步分析的目標。

關鍵字

基因體變異 ； 預後 ； 局部侵襲性大腸直腸癌 ； 比較性基因體雜交法

並列摘要

Purpose. Colorectal cancer (CRC) has become the third most common cause of cancer-related death in Taiwan. Although the prognosis of locally advanced CRC after curative surgery is generally good, about 20-30% of the patients will have the outcome similar to stage Ⅲ disease. The purpose of this study was to investigate molecular biomarkers indicative of poor prognosis in locally advanced CRC by comparative genomic hybridization (CGH).
Methods. One hundred and seventy seven patients were identified to have locally advanced CRC (pT4N0M0) from the computerized database of Taipei Veterans General Hospital between January 1980 and December 2000. Among these, 17 patients with lymph node harvest number larger than 12 were identified to have tumor recurrence (n=5) or had died of disease (n=12) (poor prognosis group) at the time of follow up. Formalin-fixed samples were available from 15 patients. Fifteen matched samples from patients free of disease (good prognosis group) were collected as control. CGH analyses were performed on these samples.
Results. CGH profiles were obtained from 12 samples of each group. The overall CGH abnormality profiles were similar for both groups. Frequent gains were found on chromosome arms 8q, 13q, 7q, and 20q; whereas common losses were found on l7p, 8p. The poor prognosis group tended to have more CGH abnormalities than did the good prognosis group (total CGH events per tumor: 4.5±4.9 vs. 3.5±3.l, p=0.56; losses: 1.8±2.4 vs. 0.8±0.8, p=0.16), especially 15q losses (15q11-q15, 15q24-q26) which appeared exclusively in the poor prognosis group (p=0.09). A further analysis disclosed that poor prognosis was significantly associated with losses on 3 or more chromosomal regions (p=0.04).
Conclusions. More genomic losses, especially 15q loss, were associated with poor prognosis in nodal negative locally advanced CRC. 15q11-15, 15q24-26 might be interesting regions for further investigation.

並列關鍵字

Genomic aberrations ； Prognosis ； Locally advanced colorectal cancer ； Comparative genomic hybridization