Unfavourable expression of pharmacologic markers in mucinous colorectal cancer
Unfavourable expression of pharmacologic markers in mucinous colorectal cancer
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DOI：
10.1038/sj.bjc.6602330
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发表时间：
2005-01-31
影响因子：
8.8
通讯作者：
McLeod, HL
中科院分区：
文献类型：
--
作者：
Glasgow, SC;Yu, J;McLeod, HL
黏液性结直肠癌患者的预后通常比非黏液性结直肠癌患者差。这种差异的原因尚不清楚，但可能是由于对辅助化疗的不同反应。我们检查了这两种组织学亚型对常见化疗反应的已知分子标记。总的来说，21例黏液性和30例非黏液性Dukes C型结直肠癌患者的人口学数据和结果进行了回顾。从肿瘤和邻近的正常粘膜中分离总RNA并进行逆转录。采用TaqMan RT - PCR检测药物通路基因的定量表达水平(5-氟尿嘧啶（5- FU）： TYMS、DPYD、ECGF1；奥沙利铂：GSTP1（谷胱甘肽S-转移酶pi）， ERCC1和2；伊立替康：ABCB1， ABCG2, CYP3A4, UGT1A1, CES2, TOP1)。与非黏液性肿瘤和患者匹配的正常粘膜相比，黏液性肿瘤显著过表达TYMS和GSTP1。其余标记物的表达无显著差异。平均随访20个月；17例复发。在接受5- FU治疗的患者中，粘液性肿瘤患者的无病生存期（DFS）短于非粘液性肿瘤患者（中位DFS为13.8个月vs 46.5个月，P = 0.053）。黏液性结直肠癌过度表达5- FU和奥沙利铂耐药标志物。同样，接受5- FU治疗的黏液性肿瘤患者的DFS也可能降低。在治疗结直肠癌的新药开发试验中，应仔细评估粘蛋白的存在。
Patients with mucinous colorectal cancer generally have worse prognoses than those with the nonmucinous variety. The reason for this disparity is unclear, but may result from a differential response to adjuvant chemotherapy. We examined known molecular markers for response to common chemotherapy in these two histological subtypes. In all, 21 patients with mucinous and 30 with nonmucinous Dukes C colorectal cancer were reviewed for demographic data and outcome. Total RNA from the tumours and adjacent normal mucosa was isolated and reverse transcribed. Quantitative expression levels of drug pathway genes were determined using TaqMan RT - PCR ( 5- fluorouracil ( 5- FU): TYMS, DPYD, ECGF1; oxaliplatin: GSTP1 ( glutathione S- transferase pi), ERCC1 and 2; irinotecan: ABCB1, ABCG2, CYP3A4, UGT1A1, CES2, TOP1). Mucinous tumours significantly overexpressed both TYMS and GSTP1 relative to nonmucinous tumours and patient- matched normal mucosa. No significant differences in expression of the remaining markers were found. Mean follow- up was 20 months; 17 patients had recurrent disease. Among patients receiving 5- FU, those with mucinous tumours experienced shorter disease- free survival ( DFS) than those with nonmucinous tumours ( median DFS 13.8 vs 46.5 months, P = 0.053). Mucinous colorectal cancer overexpresses markers of resistance to 5- FU and oxaliplatin. Likewise, DFS may be decreased in patients with mucinous tumours who receive 5- FU. The presence of mucin should be carefully evaluated in developmental trials of new agents for treating colorectal cancer.