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细胞质 Pin1 表达在人类皮肤黑色素瘤中增加,并预示预后不良。

Cytoplasmic Pin1 expression is increased in human cutaneous melanoma and predicts poor prognosis.

机构信息

Institute for laboratory Medicine, Fuzhou General Hospital, PLA, Fuzhou, Fujian, China.

Department of General Dentistry, The 174th Hospital of Chinese PLA (Chenggong Hospital affiliated to Medical School of Xiamen University), Xiamen, Fujian, China.

出版信息

Sci Rep. 2018 Nov 15;8(1):16867. doi: 10.1038/s41598-018-34906-6.

DOI:10.1038/s41598-018-34906-6
PMID:30442923
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6238011/
Abstract

The prolyl isomerase Pin1 is widely over-expressed or over-activated in cancers and promotes tumorigenesis. The authors investigated the expression level of Pin1 and analyzed the prognostic value of Pin1 expression using a large-scale melanoma tissue microarray study. Two independent sets of tissue microarrays were employed, including 114 melanoma cases in the discovery set and 424 in the validation set (538 cases in total), 32 normal nevi and 86 dysplastic nevi 118 cases of nevi. The subcellular Pin1 expression in different stages of melanocytic lesions and its prognostic significance were studied. High expression (IRS 0-8) of cytoplasmic Pin1 was observed in 3.13%, 8.33%, 16.49% and 22.76% of the biopsies in normal nevi, dysplastic nevi, primary melanoma and metastatic melanoma, respectively. Significant differences for cytoplasmic Pin1 staining were observed between normal nevi and metastatic melanoma (P = 0.011, χ test), between dysplastic nevi and primary melanoma (P = 0.046, χ test) and between dysplastic nevi and metastatic melanoma (P = 0.016, χ test). Kaplan-Meier survival analysis showed that increased cytoplasmic Pin1 expression was associated with a worse 5-year melanoma-specific survival of melanoma (P < 0.001) and metastatic melanoma patients (P = 0.004). Multivariate Cox regression analysis showed that cytoplasmic Pin1 expression is an independent prognostic factor in melanoma. Our data indicate that cytoplasmic Pin1 plays an important role in melanoma pathogenesis and progression, and serve as a potential prognostic marker for melanoma.

摘要

脯氨酰异构酶 Pin1 在癌症中广泛过表达或过度激活,促进肿瘤发生。作者通过大规模黑色素瘤组织微阵列研究,调查了 Pin1 的表达水平,并分析了 Pin1 表达的预后价值。使用了两个独立的组织微阵列集,包括发现集的 114 例黑色素瘤病例和验证集的 424 例(总计 538 例),32 例正常痣和 86 例发育不良痣 118 例痣。研究了不同阶段黑素细胞病变中细胞内 Pin1 的表达及其预后意义。在正常痣、发育不良痣、原发性黑色素瘤和转移性黑色素瘤的活检中,细胞质 Pin1 的高表达(IRS 0-8)分别观察到 3.13%、8.33%、16.49%和 22.76%。在正常痣和转移性黑色素瘤(P = 0.011,χ 检验)、发育不良痣和原发性黑色素瘤(P = 0.046,χ 检验)以及发育不良痣和转移性黑色素瘤(P = 0.016,χ 检验)之间,细胞质 Pin1 染色有显著差异。Kaplan-Meier 生存分析显示,细胞质 Pin1 表达增加与黑色素瘤(P < 0.001)和转移性黑色素瘤患者的 5 年黑色素瘤特异性生存率差相关(P = 0.004)。多变量 Cox 回归分析表明,细胞质 Pin1 表达是黑色素瘤的独立预后因素。我们的数据表明,细胞质 Pin1 在黑色素瘤发病机制和进展中起重要作用,并可作为黑色素瘤的潜在预后标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2420/6238011/caabc3dfc4cf/41598_2018_34906_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2420/6238011/ca1d667cf468/41598_2018_34906_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2420/6238011/c02e2b8bea70/41598_2018_34906_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2420/6238011/e1bf7df0a60a/41598_2018_34906_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2420/6238011/e50497d2ee22/41598_2018_34906_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2420/6238011/caabc3dfc4cf/41598_2018_34906_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2420/6238011/ca1d667cf468/41598_2018_34906_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2420/6238011/c02e2b8bea70/41598_2018_34906_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2420/6238011/e1bf7df0a60a/41598_2018_34906_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2420/6238011/e50497d2ee22/41598_2018_34906_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2420/6238011/caabc3dfc4cf/41598_2018_34906_Fig5_HTML.jpg

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Nat Commun. 2017 Jun 9;8:15772. doi: 10.1038/ncomms15772.
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PIN1 in breast development and cancer: a clinical perspective.PIN1在乳腺发育与癌症中的作用:临床视角
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The isomerase PIN1 controls numerous cancer-driving pathways and is a unique drug target.异构酶 PIN1 控制着众多致癌途径,是一个独特的药物靶点。
P4HA1 as an unfavorable prognostic marker promotes cell migration and invasion of glioblastoma via inducing EMT process under hypoxia microenvironment.
P4HA1作为一种不良预后标志物,在缺氧微环境下通过诱导上皮-间质转化过程促进胶质母细胞瘤细胞的迁移和侵袭。
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