Identification of the PCa28 Gene Signature as a Predictor in Prostate Cancer

Identification of the PCa28 Gene Signature as a Predictor in Prostate Cancer
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DOI:
10.1109/bibe.2018.00037
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发表时间:
2018-10
期刊:
2018 IEEE 18th International Conference on Bioinformatics and Bioengineering (BIBE)
影响因子:
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通讯作者:
Jung-Yu Lee;Si-Yu Lin;Yi-Hsuan Chuang;Sing-Han Huang;Yu-Yao Tseng;Chun-Yu Lin;Hung-Jung Wang;Jinn-Moon Yang
Jung-Yu Lee;Si-Yu Lin;Yi-Hsuan Chuang;Sing-Han Huang;Yu-Yao Tseng;Chun-Yu Lin;Hung-Jung Wang;Jinn-Moon Yang
中科院分区:
其他
文献类型:
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作者:
Jung-Yu Lee;Si-Yu Lin;Yi-Hsuan Chuang;Sing-Han Huang;Yu-Yao Tseng;Chun-Yu Lin;Hung-Jung Wang;Jinn-Moon Yang

文献摘要

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前列腺癌(PCa)是全球男性癌症死亡的第二大原因。大多数PCa生长缓慢,通常早期无菌。约70%的PCa患者在晚期被诊断,并已观察到转移。此外,PCa的治愈率密切依赖于生物标志物的早期诊断。前列腺特异性抗原(PSA)是目前诊断PCa的唯一临床生物标志物。然而,PSA测试具有固有的局限性,约有75%的假阳性结果。鉴定一组用于诊断和预后的基因(作为生物标志物)是PCa的迫切临床问题。在这里,我们整合了全基因组分析和蛋白质-蛋白质相互作用网络,以确定潜在的基因PCa的早期诊断生物标志物。首先,我们收集了145个PCa样本的基因表达数据集,包括肿瘤和相应的正常组织,来自基因表达综合数据库(GEO)的两个不同来源。我们在肿瘤样本中分别发现了158个和268个显著高表达和低表达的基因。此外,我们提出了聚类评分(CS)和预测评分(PS)来选择28个前列腺癌相关基因(称为PCa 28)。结果表明,PCa 28可以区分正常/肿瘤组织,并且对前列腺癌具有特异性。最后,我们用真实的实时定量聚合酶链反应(RT-qPCR)检测了PCa 28中的8个基因。实验结果表明,与正常细胞相比,上调基因在肿瘤细胞中的表达水平较高,而下调基因在肿瘤细胞中的表达水平较低。我们相信我们的方法是有用的,PCa 28是潜在的生物标志物,为PCa的靶向治疗提供线索。
Prostate cancer (PCa) is the second-leading cause of cancer death among men in the worldwide. Most PCa is slowly growing and usually early symptomless. About 70% of PCa patients were diagnosed at later stage and metastasis has been observed. Additionally, the cure rate of PCa closely relies on the early diagnosis with biomarkers. Prostatic Specific Antigen (PSA) is currently the only clinical biomarker for PCa diagnosis. However, the PSA test has inherent limitations and has about 75% of false-positive results. The identification of a set of genes (as biomarkers) for diagnosis and prognosis is an urgent clinical issue for PCa. Here, we integrated genome-wide analysis and protein-protein interaction network to identify potential genes for early diagnostic biomarkers of PCa. First, we collected gene expression datasets of 145 PCa samples, consisting of both tumor and corresponding normal tissues, from two different sources in Gene Expression Omnibus (GEO). We found 158 and 268 significantly highly and lowly expressed genes, respectively, in tumor samples. Moreover, we proposed cluster score (CS) and predicting score (PS) to select 28 prostate cancer-related genes (called PCa28). The results indicate that PCa28 can discriminate between the normal/tumor tissues and are specific for prostate cancer. Finally, we examined 8 genes in PCa28 on four PCa cell lines by real time quantitative polymerase chain reaction (RT-qPCR). Experimental results show that up-regulated genes have higher expression level in tumor cells in comparison to normal cells, and down-regulated genes have lower expression level in tumor cells. We believe that our method is useful and PCa28 are potential biomarkers that provide the clues to develop targeting therapy for PCa.