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对胰腺微阵列数据集的荟萃分析产生了新的癌症基因和生物标志物靶标。

A meta analysis of pancreatic microarray datasets yields new targets as cancer genes and biomarkers.

机构信息

Department of Chemistry and Biochemistry, University of Northern Iowa, Cedar Falls, Iowa, United States of America.

Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, Nebraska, United States of America.

出版信息

PLoS One. 2014 Apr 16;9(4):e93046. doi: 10.1371/journal.pone.0093046. eCollection 2014.

Abstract

The lack of specific symptoms at early tumor stages, together with a high biological aggressiveness of the tumor contribute to the high mortality rate for pancreatic cancer (PC), which has a five year survival rate of less than 5%. Improved screening for earlier diagnosis, through the detection of diagnostic and prognostic biomarkers provides the best hope of increasing the rate of curatively resectable carcinomas. Though many serum markers have been reported to be elevated in patients with PC, so far, most of these markers have not been implemented into clinical routine due to low sensitivity or specificity. In this study, we have identified genes that are significantly upregulated in PC, through a meta-analysis of large number of microarray datasets. We demonstrate that the biological functions ascribed to these genes are clearly associated with PC and metastasis, and that that these genes exhibit a strong link to pathways involved with inflammation and the immune response. This investigation has yielded new targets for cancer genes, and potential biomarkers for pancreatic cancer. The candidate list of cancer genes includes protein kinase genes, new members of gene families currently associated with PC, as well as genes not previously linked to PC. In this study, we are also able to move towards developing a signature for hypomethylated genes, which could be useful for early detection of PC. We also show that the significantly upregulated 800+ genes in our analysis can serve as an enriched pool for tissue and serum protein biomarkers in pancreatic cancer.

摘要

早期肿瘤阶段缺乏特异性症状,加上肿瘤的高生物侵袭性,导致胰腺癌(PC)的死亡率很高,五年生存率低于 5%。通过检测诊断和预后生物标志物进行早期诊断的改进筛查,为提高可治愈性切除癌的比例提供了最大的希望。尽管已经报道了许多血清标志物在 PC 患者中升高,但迄今为止,由于敏感性或特异性低,这些标志物中的大多数尚未纳入临床常规。在这项研究中,我们通过对大量微阵列数据集进行荟萃分析,确定了在 PC 中显著上调的基因。我们证明,归因于这些基因的生物学功能显然与 PC 和转移有关,这些基因与涉及炎症和免疫反应的途径密切相关。这项研究为癌症基因和胰腺癌的潜在生物标志物提供了新的靶点。候选的癌症基因列表包括蛋白激酶基因、目前与 PC 相关的基因家族的新成员,以及以前与 PC 无关的基因。在这项研究中,我们还能够朝着开发低甲基化基因特征的方向发展,这对早期发现 PC 可能有用。我们还表明,我们分析中显著上调的 800 多个基因可以作为胰腺癌组织和血清蛋白生物标志物的富集池。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1a8/3989178/ac1c435f71a4/pone.0093046.g001.jpg

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