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血红素加氧酶-1 种系 GTn 启动子多态性是胰腺癌肿瘤复发和生存的独立预后因子。

Heme oxygenase-1 germ line GTn promoter polymorphism is an independent prognosticator of tumor recurrence and survival in pancreatic cancer.

机构信息

Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

出版信息

J Surg Oncol. 2011 Sep 1;104(3):305-11. doi: 10.1002/jso.21926. Epub 2011 Apr 14.

DOI:10.1002/jso.21926
PMID:21495030
Abstract

BACKGROUND

Heme oxygenase-1 (HO-1) correlates with aggressive tumor behavior and chemotherapy resistance in pancreatic cancer (PC). We evaluated the prognostic value of the basal transcription controlling germ line GTn repeat polymorphism (GTn) in the promoter region of the HO-1 gene in PC.

PATIENTS AND METHODS

We determined the GTn in 100 controls and 150 PC patients. DNA was extracted from blood leukocytes and GTn determined by PCR, electrophoresis, and sequencing. Clinicopathological parameters, disease-free, and overall survival (DFS, OS) were correlated with GTn.

RESULTS

Three genotypes were defined based on short (S) <25 and long (L) ≥25 GTn repeat alleles. In PC patients, a steadily increasing risk was evident between LL, SL, and SS genotype patients for larger tumor size, presence of lymph node metastasis, poor tumor differentiation and higher recurrence rate (P < 0.001 each). The SS genotype displayed the most aggressive tumor biology. The LL genotype had the best and the SS genotype the worst DFS and OS (P < 0.001 each). The GTn genotype was the strongest prognostic factor for recurrence and survival (P < 0.001 each).

CONCLUSION

The GTn repeat polymorphism is a strong prognostic marker for recurrence and survival in PC patients.

摘要

背景

血红素加氧酶-1(HO-1)与胰腺癌(PC)中的侵袭性肿瘤行为和化疗耐药性相关。我们评估了 HO-1 基因启动子区域基本转录调控种系 GTn 重复多态性(GTn)的基础转录对 PC 的预后价值。

患者和方法

我们在 100 名对照者和 150 名 PC 患者中确定了 GTn。从血液白细胞中提取 DNA,通过 PCR、电泳和测序确定 GTn。临床病理参数、无病和总生存(DFS、OS)与 GTn 相关。

结果

根据短(S)<25 和长(L)≥25 GTn 重复等位基因,定义了三种基因型。在 PC 患者中,LL、SL 和 SS 基因型患者的肿瘤大小较大、存在淋巴结转移、肿瘤分化不良和复发率较高(P<0.001 )。SS 基因型显示出最具侵袭性的肿瘤生物学。LL 基因型的 DFS 和 OS 最好,SS 基因型最差(均 P<0.001 )。GTn 基因型是复发和生存的最强预后因素(均 P<0.001 )。

结论

GTn 重复多态性是 PC 患者复发和生存的强预后标志物。

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