Department of Pathology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Department of Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
PLoS One. 2018 Apr 9;13(4):e0195354. doi: 10.1371/journal.pone.0195354. eCollection 2018.
Over 1.4 million people are diagnosed with colorectal cancer (CRC) each year, making it the third most common cancer in the world. Increased screening and therapeutic modalities including improved combination treatments have reduced CRC mortality, although incidence and mortality rates are still increasing in some areas. Serum-based biomarkers are mainly used for follow-up of cancer, and are ideal due to the ease and minimally invasive nature of sample collection. Unfortunately, CEA and other serum markers have too low sensitivity for screening and preoperative diagnostic purposes. Increasing interest is focused on the possible use of biomarkers for predicting treatment response and prognosis in cancer. In this study, we have performed mass spectrometry analysis (UPLC-UDMSE) of serum samples from 19 CRC patients. Increased levels of C-reactive protein (CRP), which occur during local inflammation and the presence of a systemic inflammatory response, have been linked to poor prognosis in CRC patients. We chose to analyze samples according to CRP values by dividing them into the categories CRP <30 and >30, and, separately, according to short and long 5-year survival. The aim was to discover differentially expressed proteins associated with poor prognosis and shorter survival. We quantified 256 proteins and performed detailed statistical analyses and pathway analysis. We discovered multiple proteins that are up- or downregulated in patients with CRP >30 as compared to CRP <30 and in patients with short as compared to long 5-year survival. Pathways that were enriched include LXR/RXR activation, FXR/RXR activation, complement and coagulation cascades and acute phase signaling response, with some of the proteins we identified having roles in these pathways. In this study, we have identified multiple proteins, of which a few have been previously identified as potential biomarkers, and others that have been identified as potential biomarkers for CRC for the first time, to the best of our knowledge. While these proteins still need to be validated in larger patient series, this pilot study will pave the way for future studies aiming to provide better biomarkers for patients with CRC.
每年有超过 140 万人被诊断患有结直肠癌（CRC），使其成为世界上第三常见的癌症。增加筛查和治疗方式，包括改进的联合治疗，已经降低了 CRC 的死亡率，尽管在某些地区，发病率和死亡率仍在上升。基于血清的生物标志物主要用于癌症的随访，并且由于样本采集的简便性和微创性而成为理想的选择。不幸的是，CEA 和其他血清标志物用于筛查和术前诊断的灵敏度太低。越来越多的人关注生物标志物在预测癌症治疗反应和预后方面的可能用途。在这项研究中，我们对 19 名 CRC 患者的血清样本进行了质谱分析（UPLC-UDMSE）。C 反应蛋白（CRP）在局部炎症和全身炎症反应期间升高，与 CRC 患者的不良预后相关。我们选择根据 CRP 值分析样本，将其分为 CRP<30 和>30 两类，并且根据 5 年短期和长期生存分别进行分析。目的是发现与不良预后和较短生存相关的差异表达蛋白。我们定量了 256 种蛋白质，并进行了详细的统计分析和途径分析。我们发现了多个在 CRP>30 的患者中上调或下调的蛋白质，与 CRP<30 的患者相比，与 5 年短期生存的患者相比，这些蛋白质的表达水平有所不同。富集的途径包括 LXR/RXR 激活、FXR/RXR 激活、补体和凝血级联以及急性期信号反应，我们鉴定的一些蛋白质在这些途径中起作用。在这项研究中，我们已经确定了多种蛋白质，其中一些先前已被鉴定为潜在的生物标志物，而其他一些则是首次被鉴定为 CRC 的潜在生物标志物，据我们所知。虽然这些蛋白质仍需要在更大的患者系列中进行验证，但这项初步研究将为未来旨在为 CRC 患者提供更好的生物标志物的研究铺平道路。
