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PRL-3基因的基因组扩增可能预示原发性结直肠癌预后不良,并与肝转移相关。

Genomic gain of the PRL-3 gene may represent poor prognosis of primary colorectal cancer, and associate with liver metastasis.

作者信息

Nakayama N, Yamashita K, Tanaka T, Kawamata H, Ooki A, Sato T, Nakamura T, Watanabe M

机构信息

Department of Surgery, Kitasato University School of Medicine, Asamizodai 2-1-1, Minami-ku, Sagamihara, Kanagawa, 252-0380, Japan.

出版信息

Clin Exp Metastasis. 2016 Jan;33(1):3-13. doi: 10.1007/s10585-015-9749-7. Epub 2015 Nov 12.

DOI:10.1007/s10585-015-9749-7
PMID:26563151
Abstract

PRL-3 genomic copy number is increased in colorectal cancer (CRC), and PRL-3 expression is closely associated with lymph node and liver metastasis of CRC. However, the clinical significance of PRL-3 genomic gain for CRC remains obscure. Here, PRL-3 genomic status in 109 primary CRC tumors and in 44 CRC tumors that had metastasized to the liver, was quantified using real time PCR. Association of PRL-3 genomic status with clinicopathological factors and prognosis was assessed in detail. PRL-3 genomic gain was identified in 31 primary CRC (27.4 %) and was more frequently seen in stage III than in stage II (p = 0.025). Among the clinicopathological factors assessed, PRL-3 genomic gain was significantly associated with poorly differentiated histology (p = 0.0039). Moreover, CRC patients with PRL-3 genomic gain exhibited poorer prognosis than those with no gain in stage II-IV CRC (p = 0.017). PRL-3 genomic gain was identified in 18 (41 %) of the liver metastasis tumors, and this frequency of gain was significantly increased as compared to that of the corresponding primary CRCs (11 %) (p = 0.001). Our findings suggested that PRL-3 genomic gain may represent an aggressive phenotype of primary CRC, and may associate with liver metastasis.

摘要

结直肠癌(CRC)中PRL - 3基因拷贝数增加,且PRL - 3表达与CRC的淋巴结及肝转移密切相关。然而,PRL - 3基因增益对CRC的临床意义仍不清楚。在此,采用实时PCR对109例原发性CRC肿瘤及44例已发生肝转移的CRC肿瘤中的PRL - 3基因状态进行定量分析。详细评估PRL - 3基因状态与临床病理因素及预后的相关性。在31例原发性CRC(27.4%)中检测到PRL - 3基因增益,且在III期比II期更常见(p = 0.025)。在评估的临床病理因素中,PRL - 3基因增益与低分化组织学显著相关(p = 0.0039)。此外,在II - IV期CRC中,PRL - 3基因增益的患者预后比无增益的患者差(p = 0.017)。在18例(41%)肝转移肿瘤中检测到PRL - 3基因增益,与相应原发性CRC(11%)相比,这种增益频率显著增加(p = 0.001)。我们的研究结果表明,PRL - 3基因增益可能代表原发性CRC的侵袭性表型,并可能与肝转移相关。

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本文引用的文献

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Large-scale genetic study in East Asians identifies six new loci associated with colorectal cancer risk.针对东亚人群的大规模基因研究发现了六个与结直肠癌风险相关的新基因座。
Nat Genet. 2014 Jun;46(6):533-42. doi: 10.1038/ng.2985. Epub 2014 May 18.
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LEO1 is regulated by PRL-3 and mediates its oncogenic properties in acute myelogenous leukemia.LEO1 通过 PRL-3 调控并在急性髓性白血病中发挥其致癌特性。
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Poor prognosis of phosphatase of regenerating liver 3 expression in gastric cancer: a meta-analysis.
循环肿瘤细胞中间充质和肝再生磷酸酶 3 状态可作为评估结直肠癌术后患者复发或转移的关键预后标志物。
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Prospective validation in epithelial tumors of a gene expression predictor of liver metastasis derived from uveal melanoma.从葡萄膜黑素瘤衍生的肝转移基因表达预测因子在上皮性肿瘤中的前瞻性验证。
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Critical relevance of genomic gains of PRL-3/EGFR/c-myc pathway genes in liver metastasis of colorectal cancer.PRL-3/EGFR/c-myc通路基因的基因组增益在结直肠癌肝转移中的关键相关性
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胃癌中再生肝磷酸酶3表达的预后不良:一项荟萃分析。
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