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首页> 外文期刊>BMC Medical Genomics >Biomarker expression patterns that correlate with high grade features in treatment naive, organ-confined prostate cancer
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Biomarker expression patterns that correlate with high grade features in treatment naive, organ-confined prostate cancer

机译：与未治疗的器官受限型前列腺癌的高级特征相关的生物标志物表达模式

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Background: The early detection of prostate cancer has resulted in an increase in the number of patients with localized prostate cancer and has paralleled the reported reduction in prostate cancer mortality. The increased rate of detection of patients with localized prostate cancer may also increase the risk of potentially morbid therapy in a patient with indolent cancer. Defining the biomarker correlates of prostate cancer virulence will facilitate the appropriate application and development of therapy for patients with early disease. Methods: A 255 core prostate cancer tissue microarray (TMA) from 47 prostatectomy specimens with organ confined tumor was constructed. Prostate cancer foci of transition and peripheral zone origin were represented on the TMA. Further, replicate cores of the two Gleason grades comprising the Gleason score, representative of Gleason scores 5-9, were arrayed from each prostatectomy specimen. Standard immunohistochemical techniques were used to assess expression of nine, cell death and cell cycle regulatory proteins implicated in the pathogenesis of prostate cancer (bax, bcl-2, bcl-xL, bin1, CD95, mdm2, p21, p53, and NFkB). Results: The Spearman correlation coefficient revealed a strong correlation of bax, bin1, FAS, p65 and p21 expression with Gleason grade. Spearman correlation coefficients showed that expression of, bax and bin1, bax and MDM2, Bax and p21, and bax and p65 NFkB was highly associated. Other significant associations were identified between bin1 and p21, bin1 and MDM2, bin1 and p65 NFkB and between p21 and p65 NFκB. A model for predicting the biological potential of Gleason score 7 prostate cancer using multivariable logistic regression methods was developed. The findings also indicate that the profile of specific markers for Gleason grade 3 prostate cancer correlates with the overall context of the Gleason score. Conclusion: These data support the view that important molecular differences exist among and between the Gleason scores. Furthermore, there is significant molecular heterogeneity among prostatectomy specimens containing Gleason grade 3 cancer. This observation may have broader implications regarding the determination of risk among patients with prostate cancer that is currently considered to be of either good prognosis or unclear prognosis, i.e. Gleason score 7 tumors.
机译：背景：前列腺癌的早期发现导致局限性前列腺癌的患者数量增加，并且与前列腺癌死亡率的降低相提并论。局限性前列腺癌患者的检出率升高也可能增加惰性癌症患者潜在病态治疗的风险。定义前列腺癌毒力的生物标志物的相关性将有助于早期疾病患者的治疗的适当应用和发展。方法：从47例前列腺切除术标本中有器官局限性肿瘤的患者中构建255个核心前列腺癌组织芯片（TMA）。 TMA代表了前列腺癌的转移灶和外周带起源。此外，从每个前列腺切除术标本排列包括格里森评分的两个格里森评分的重复核心，代表格里森评分5-9。标准免疫组织化学技术用于评估涉及前列腺癌发病机理的9种细胞死亡蛋白和细胞周期调节蛋白的表达（bax，bcl-2，bcl-x L ，bin1，CD95，mdm2， p21，p53和NFkB）。结果：Spearman相关系数显示bax，bin1，FAS，p65和p21表达与Gleason等级密切相关。 Spearman相关系数显示bax和bin1，bax和MDM2，Bax和p21以及bax和p65 NFkB的表达高度相关。在bin1和p21，bin1和MDM2，bin1和p65 NFkB之间以及p21和p65NFκB之间还发现了其他重要关联。建立了使用多变量逻辑回归方法预测格里森评分为7的前列腺癌的生物潜力的模型。这些发现还表明，格里森3级前列腺癌的特定标志物的概况与格里森评分的整体情况相关。结论：这些数据支持这样的观点，即格里森评分之间和之间存在重要的分子差异。此外，在包含格里森3级癌症的前列腺切除术标本中，存在明显的分子异质性。对于目前被认为预后良好或预后不明确的前列腺癌患者（即格里森评分为7的肿瘤）中的风险确定，该观察结果可能具有更广泛的含义。

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