Prolyl 4-hydroxylase alpha 1 protein expression risk-stratifies early stage colorectal cancer.
Prolyl 4-hydroxylase alpha 1 protein expression risk-stratifies early stage colorectal cancer.
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DOI：
10.18632/oncotarget.27491
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发表时间：
2020-02-25
期刊：
影响因子：
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通讯作者：
Roehrl, Michael H
中科院分区：
文献类型：
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作者：
Tanaka, Atsushi;Zhou, Yihua;Roehrl, Michael H
结直肠癌(CRC)是世界上最常见、最致命的恶性肿瘤之一。尤其对于早期结直肠癌，需要预后分子标志物来指导治疗。在这项研究中，我们首先从22例大肠癌患者的新鲜癌组织和良性黏膜组织中提取了匹配的总蛋白质组。用傅立叶变换液-质联用测序和无标记定量的整体蛋白质组分析发现，P4HA1(Prolyl 4-Hylase Alpha 1)在结直肠癌中高表达，相对于良性结肠黏膜。然后，我们通过使用CRC组织芯片的P4HA1特异性抗体的免疫组织化学染色来研究其表达。对599例早期结直肠癌和91例晚期结直肠癌进行了独立验证队列研究。多因素和单因素生存分析显示，P4HA1蛋白高表达是早期结直肠癌患者预后不良的独立指标，尤其是微卫星稳定亚型。我们的研究为P4HA1作为早期结直肠癌精确诊断、治疗决策和药物开发的预测蛋白质标志物提供了强有力的支持，并证明了蛋白质组学分析在识别新的蛋白质生物标志物方面的应用。
Colorectal cancer (CRC) is one of the most prevalent and lethal malignancies. Especially for early stage CRC, prognostic molecular markers are needed to guide therapy. In this study, we first extracted total proteomes from matched pairs of fresh cancer and benign mucosal tissues from 22 CRC patients. Global proteomic profiling with Fourier transform liquid chromatography-mass spectrometry sequencing and label free quantitation uncovered that P4HA1 (prolyl 4-hydroxylase alpha 1) was overexpressed in CRC relative to benign colonic mucosa. We then investigated expression by immunohistochemical staining with P4HA1-specific antibodies using CRC tissue microarrays. Independent validation cohorts of 599 cases of early stage CRC and 91 cases of late stage CRC were examined. Multivariate and univariate survival analyses revealed that high expression of P4HA1 protein was an independent poor prognostic marker for patients with early stage CRC, especially of the microsatellite stable subtype. Our study provides strong support for P4HA1 as a predictive protein marker for precision diagnostics, therapeutic decision-making, and drug development for early stage colorectal cancer and demonstrates the utility of proteomic profiling to identify novel protein biomarkers.