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线粒体 DNA 拷贝数是否是可切除胰腺癌的一个良好预后标志物?

Is mitochondrial DNA copy number a good prognostic marker in resectable pancreatic cancer?

机构信息

Department of Surgical Research and Transplantology, Medical Research Centre Polish Academy of Sciences, Warsaw, Poland; Diagnostic Radiology Department, Central Clinical Hospital of the MSWiA in Warsaw, Poland.

Department of Neurochemistry, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.

出版信息

Pancreatology. 2019 Jan;19(1):73-79. doi: 10.1016/j.pan.2018.11.009. Epub 2018 Nov 22.

Abstract

BACKGROUND

The aim of this prospective study was to investigate mitochondrial DNA (mtDNA) copy number in a group of resectable pancreatic cancer (PC) tumor tissues and adjacent normal pancreatic tissues, and to explore the correlation between the mtDNA content in tissues and the clinicopathological parameters and the overall survival.

METHODS

Relative mtDNA copy number was measured by the quantitative PCR-based assay. The tumors specimens (n = 43) originated from the patients with pathologically confirmed pancreatic ductal adenocarcinoma who did not receive any neoadjuvant systemic therapy. The adjacent normal pancreatic tissue samples (n = 31) were obtained from surgical margins.

RESULTS

mtDNA copy number was significantly lower in PC tissue (P < 0.001) compared to adjacent normal pancreatic tissue. Jonckheere-Terpstra trend testing indicated a statistically significant decrease in median mtDNA copy number across the differentiation (adjacent normal pancreatic tissue, low-grade, intermediate-grade, high-grade cancer), P < 0.001. However, the survival analyses failed to show a significant difference in survival between patients with high and low mtDNA copy number.

CONCLUSIONS

To the best of our knowledge, we provided the first evidence that mitochondrial DNA copy number was significantly lower in pancreatic cancer tissue (P < 0.001) compared to adjacent normal pancreatic tissue. Also, we demonstrated that mitochondrial copy number was not a significant marker for predicting prognosis in resectable pancreatic cancer.

摘要

背景

本前瞻性研究旨在检测一组可切除胰腺癌(PC)肿瘤组织和相邻正常胰腺组织中的线粒体 DNA(mtDNA)拷贝数,并探讨组织中 mtDNA 含量与临床病理参数和总生存期之间的相关性。

方法

采用基于定量 PCR 的方法检测相对 mtDNA 拷贝数。肿瘤标本(n=43)来自未经新辅助系统治疗的病理证实为胰腺导管腺癌的患者。相邻的正常胰腺组织样本(n=31)取自手术边缘。

结果

与相邻正常胰腺组织相比,PC 组织中的 mtDNA 拷贝数显著降低(P<0.001)。Jonckheere-Terpstra 趋势检验表明,mtDNA 拷贝数中位数在分化程度(相邻正常胰腺组织、低级别、中级别、高级别癌症)中呈显著下降趋势,P<0.001。然而,生存分析未能显示高 mtDNA 拷贝数和低 mtDNA 拷贝数患者之间的生存存在显著差异。

结论

据我们所知,我们首次提供了证据,表明与相邻正常胰腺组织相比,胰腺癌组织中的线粒体 DNA 拷贝数显著降低(P<0.001)。此外,我们还证明线粒体拷贝数不是预测可切除胰腺癌预后的显著标志物。

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