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人类白细胞抗原I类抗原表达是卵巢癌的一个独立预后因素。

Human leukocyte antigen class I antigen expression is an independent prognostic factor in ovarian cancer.

作者信息

Rolland Phil, Deen Suha, Scott Ian, Durrant Lindy, Spendlove Ian

机构信息

Academic and Clinical Department of Oncology, University Hospitals Nottingham, City Hospital Campus, Nottingham, United Kingdom.

出版信息

Clin Cancer Res. 2007 Jun 15;13(12):3591-6. doi: 10.1158/1078-0432.CCR-06-2087.

Abstract

PURPOSE

Despite improvements in cancer treatment, the prognosis of ovarian cancer remains low and imperfectly predicted by traditional pathologic criteria. Biomarkers that predict prognosis independently of such criteria shed light on important molecular variations, aiding in the development and targeting of novel therapies. Previous work has shown human leukocyte antigen (HLA) class I antigen expression to be independently predictive of prognosis in colorectal and breast cancer. We investigated the prognostic potential of HLA class I antigen expression by studying a large series of ovarian cancers.

EXPERIMENTAL DESIGN

A tissue microarray of 339 ovarian cancer cases linked to prospectively recorded clinicopathologic and follow-up data was constructed. This was stained following a standard immunohistochemical protocol for HLA class I heavy chain (HC-10) and beta(2)-microglobulin (beta(2)-m). HLA class I antigen expression was compared with clinicopathologic factors and overall disease-specific survival using the Pearson chi(2) test, Kaplan-Meier curves, and the log-rank test. Cox regression was used to test for the independence and magnitude of effects.

RESULTS

There were no univariate correlations between HLA class I antigen expression and clinicopathologic factors. Deviation from an HC-10(+)/beta(2)-m(+) phenotype correlated with reduced survival in univariate analysis (log-rank, 5.69; P = 0.017); a retained HC-10(+)/beta(2)-m(+) phenotype predicted improved prognosis independently of age, stage, level of cytoreduction, and chemotherapy usage on multivariate analysis (hazard ratio, 0.587; 95% confidence interval, 0.442-0.781; P < 0.001).

CONCLUSIONS

HLA class I antigen expression is an independent prognostic marker in ovarian cancer, its loss correlating with a poor prognostic outcome.

摘要

目的

尽管癌症治疗有所改善,但卵巢癌的预后仍然很差,且传统病理标准对其预测并不完善。独立于这些标准预测预后的生物标志物有助于揭示重要的分子变异,从而有助于新型疗法的开发和靶向治疗。先前的研究表明,人类白细胞抗原(HLA)I类抗原表达可独立预测结直肠癌和乳腺癌的预后。我们通过研究大量卵巢癌病例来探讨HLA I类抗原表达的预后潜力。

实验设计

构建了一个包含339例卵巢癌病例的组织微阵列,并与前瞻性记录的临床病理和随访数据相关联。按照HLA I类重链(HC-10)和β2微球蛋白(β2-m)的标准免疫组织化学方案对其进行染色。使用Pearson卡方检验、Kaplan-Meier曲线和对数秩检验,将HLA I类抗原表达与临床病理因素及总体疾病特异性生存率进行比较。采用Cox回归检验效应的独立性和大小。

结果

HLA I类抗原表达与临床病理因素之间不存在单变量相关性。在单变量分析中,偏离HC-10(+)/β2-m(+)表型与生存率降低相关(对数秩,5.69;P = 0.017);在多变量分析中,保留HC-10(+)/β2-m(+)表型独立于年龄、分期、细胞减灭水平和化疗使用情况预测预后改善(风险比,0.587;95%置信区间,0.442 - 0.781;P < 0.001)。

结论

HLA I类抗原表达是卵巢癌的独立预后标志物,其缺失与不良预后相关。

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