Proteomic analyses identify major vault protein as a prognostic biomarker for fatal prostate cancer.
Proteomic analyses identify major vault protein as a prognostic biomarker for fatal prostate cancer.
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DOI：
10.1093/carcin/bgab015
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发表时间：
2021-05-28
期刊：
影响因子：
4.7
通讯作者：
Andersen S
中科院分区：
文献类型：
--
作者：
Ramberg H;Richardsen E;de Souza GA;Rakaee M;Stensland ME;Braadland PR;Nygård S;Ögren O;Guldvik IJ;Berge V;Svindland A;Taskén KA;Andersen S
人口向老年人口的转变将增加前列腺癌病例的数量。前列腺癌治疗中的一个挑战是避免治愈性治疗后进展风险高的患者治疗不足。这些人可以从早期抢救治疗中获益。通过质谱分析，对16例接受根治性前列腺切除术的患者的组织进行了探索性队列分析，这些患者在术后10年内存活或死于前列腺癌。在蛋白质组学和生物信息学分析之后，主穹窿蛋白（MVP）被鉴定为推定的预后生物标志物。公开可用的组织蛋白质组学数据集和368例前列腺癌患者的回顾性队列用于验证。MVP的预后价值通过组织芯片的免疫组化染色评分来验证。在考克斯比例风险模型中，高水平MVP与前列腺癌死亡风险增加4倍以上相关（风险比= 4.41，95%置信区间：1.45-13.38; P = 0.009），校正了前列腺癌术后风险评估（CAPRA-S）评分和神经浸润。决策曲线分析表明，将MVP添加到CAPRA-S评分中的标准化净获益有所改善，范围为0.06 - 0.18。CAPRA-S评分与CAPRA-S和MVP评分的受试者操作特征曲线分析证实了这一观察结果（曲线下面积：0. 58与0. 73）。从这些分析中，可以推断MVP水平与CAPA-S评分的组合可能会增加已建立的风险参数，以识别患有致命前列腺癌的患者。探索性队列的质谱鉴定出一种有前景的生物标志物，主要穹窿蛋白。使用两个独立的验证队列，我们验证了高MVP和不良结局之间的关联。MVP与前列腺癌特异性死亡相关，独立于复合风险模型。
The demographic shift toward an older population will increase the number of prostate cancer cases. A challenge in the treatment of prostate cancer is to avoid undertreatment of patients at high risk of progression following curative treatment. These men can benefit from early salvage treatment. An explorative cohort consisting of tissue from 16 patients who underwent radical prostatectomy, and were either alive or had died from prostate cancer within 10 years postsurgery, was analyzed by mass spectrometry analysis. Following proteomic and bioinformatic analyses, major vault protein (MVP) was identified as a putative prognostic biomarker. A publicly available tissue proteomics dataset and a retrospective cohort of 368 prostate cancer patients were used for validation. The prognostic value of the MVP was verified by scoring immunohistochemical staining of a tissue microarray. High level of MVP was associated with more than 4-fold higher risk for death from prostate cancer (hazard ratio = 4.41, 95% confidence interval: 1.45–13.38; P = 0.009) in a Cox proportional hazard models, adjusted for Cancer of the Prostate Risk Assessments Post-surgical (CAPRA-S) score and perineural invasion. Decision curve analyses suggested an improved standardized net benefit, ranging from 0.06 to 0.18, of adding MVP onto CAPRA-S score. This observation was confirmed by receiver operator characteristics curve analyses for the CAPRA-S score versus CAPRA-S and MVP score (area under the curve: 0.58 versus 0.73). From these analyses, one can infer that MVP levels in combination with CAPRA-S score might add onto established risk parameters to identify patients with lethal prostate cancer. Mass spectrometry of an explorative cohort identified a promising biomarker, major vault protein. Using two independent validation cohorts, we verified an association between high MVP and adverse outcome. MVP was associated with prostate cancer-specific death independently of a composite risk model.
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影响因子：
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作者：
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通讯作者：
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影响因子：
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DOI：
10.1083/jcb.103.3.699
发表时间：
1986-09
期刊：
The Journal of cell biology
影响因子：
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作者：
Kedersha NL;Rome LH
通讯作者：
Rome LH
DOI：
10.1093/jnci/djy088
发表时间：
2018-08-01
期刊：
Journal of the National Cancer Institute
影响因子：
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通讯作者：
Altman DG