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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >B7-H3 and B7x are highly expressed in human prostate cancer and associated with disease spread and poor outcome
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B7-H3 and B7x are highly expressed in human prostate cancer and associated with disease spread and poor outcome

机译：B7-H3和B7x在人类前列腺癌中高表达，并与疾病传播和不良预后相关

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摘要

B7-H3 and B7x are recently discovered members of the B7-CD28 family thought to dampen peripheral immune responses via negative costimulation. We evaluated their potential expression in human prostate cancer using a large cohort of patients with 7 years of follow-up. We identified 823 patients with tissue available treated with radical prostatectomy between 1985 and 2003. Im-munohistochemistry was performed on tissue microarray sections using anti-B7-H3 and -B7x. The percentage and intensity of immu-noreactivity by tumor cells were blindly evaluated by two urolog-ical pathologists, and outcome analyses were conducted. Both B7-H3 and B7x were highly expressed; 93% and 99% of tumors had aberrant expression, respectively. The median percentage of tumor cells staining positive was 80% for each molecule. Strong intensity for B7-H3 and B7x was noted in 212 (26%) and 120 (15%) patients, respectively. Patients with strong intensity for B7-H3 and B7x were significantly more likely to have disease spread at time of surgery (P < 0.001 and P = 0.005, respectively). Additionally, patients with strong intensity for B7-H3 and B7x were at significantly increased risk of clinical cancer recurrence (P < 0.001 and P = 0.005) and cancer-specific death (P = 0.004 and P = 0.04, respectively). To our knowledge, we present the largest investigation of B7 family molecules in a human malignancy and a previously undescribed evaluation of B7x in prostate cancer. B7-H3 and B7x are abundantly expressed in prostate cancer and associated with disease spread and poor outcome. Given the proposed immune-inhibitory mechanisms of B7-H3 and B7x, these molecules represent attractive targets for therapeutic manipulation in prostate cancer.
机译：B7-H3和B7x是最近发现的B7-CD28家族成员，被认为可通过负共刺激抑制外周免疫反应。我们使用了一大批经过7年随访的患者，评估了它们在人前列腺癌中的潜在表达。我们确定了1985年至2003年之间有823例接受前列腺癌根治术治疗的组织患者。使用抗B7-H3和-B7x对组织微阵列切片进行了免疫组织化学。由两名泌尿科病理学家盲目评估了肿瘤细胞免疫反应的百分比和强度，并进行了结果分析。 B7-H3和B7x均高表达；分别有93％和99％的肿瘤表达异常。每个分子染色阳性的肿瘤细胞的中值百分比为80％。分别在212名（26％）和120名（15％）患者中发现了B7-H3和B7x的强强度。 B7-H3和B7x强度高的患者在手术时更容易患病（分别为P <0.001和P = 0.005）。此外，B7-H3和B7x强度高的患者发生临床癌症复发的风险显着增加（P <0.001和P = 0.005）和特定于癌症的死亡（分别为P = 0.004和P = 0.04）。据我们所知，我们提出了人类恶性肿瘤中B7家族分子的最大研究，以及对前列腺癌中B7x的先前未描述的评估。 B7-H3和B7x在前列腺癌中大量表达，并与疾病扩散和不良预后相关。考虑到拟议的B7-H3和B7x免疫抑制机制，这些分子代表了前列腺癌治疗操作的诱人靶标。

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