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血清 LOX-1 是结直肠癌的一种新型预后生物标志物。

Serum LOX-1 is a novel prognostic biomarker of colorectal cancer.

机构信息

Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi, 755-8505, Japan.

Department of Translational Research and Developmental Therapeutics against Cancer, Yamaguchi University School of Medicine, Ube, Japan.

出版信息

Int J Clin Oncol. 2020 Jul;25(7):1308-1317. doi: 10.1007/s10147-020-01673-2. Epub 2020 Apr 11.

Abstract

BACKGROUND

Colorectal cancer is the third most common cancer worldwide. If biomarkers can be identified in liquid biopsy, diagnosis and treatment can be optimized even when cancerous tissues are not available. The purpose of this study was to identify proteins from liquid biopsy that would be useful as markers of poor prognosis.

METHODS

First, we comprehensively analyzed serum proteins to identify potential biomarkers and focused on serum lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1). The relationship between LOX-1 and the prognosis of patients with colorectal cancer has not been reported. Next, we validated this marker using serum samples from 238 patients with colorectal cancer by ELISA and 100 tissue samples by immunohistochemical staining.

RESULTS

The optimal cut-off value of serum LOX-1 was 538.7 pg/mL according to time-dependent receiver operating characteristics curve analysis. The overall survival of patients with high levels of serum LOX-1 was significantly poorer than that of individuals with low levels of LOX-1 in the training and test datasets. In multivariate analysis for overall survival, serum LOX-1 was an independent prognostic factor identified in liquid biopsy (hazard ratio = 1.729, p = 0.027). The prognosis of patients with high LOX-1 expression in tumor tissues was significantly poorer than that of individuals with low expression (p =0.047 ). Additionally, inflammatory factors such as white blood cell count, C-reactive protein level, neutrophil/lymphocyte ratio, and monocyte/lymphocyte ratio were significantly higher in the group with high serum LOX-1 levels.

CONCLUSIONS

Serum LOX-1 might be a useful biomarker of poor prognosis in colorectal cancer.

摘要

背景

结直肠癌是全球第三大常见癌症。如果能在液体活检中识别出生物标志物,即使无法获得癌组织,也能优化诊断和治疗。本研究旨在确定液体活检中可作为不良预后标志物的蛋白质。

方法

首先,我们全面分析了血清蛋白,以鉴定潜在的生物标志物,并重点研究了血清凝集素样氧化型低密度脂蛋白受体-1(LOX-1)。LOX-1 与结直肠癌患者预后之间的关系尚未有报道。接下来,我们通过 ELISA 检测了 238 例结直肠癌患者的血清样本和 100 例组织样本,验证了该标志物。

结果

根据时间依赖性受试者工作特征曲线分析,血清 LOX-1 的最佳截断值为 538.7 pg/mL。高 LOX-1 血清水平患者的总生存期明显短于训练和测试数据集低 LOX-1 血清水平患者。多变量分析显示,血清 LOX-1 是液体活检中独立的预后因素(危险比=1.729,p=0.027)。肿瘤组织中 LOX-1 高表达患者的预后明显差于 LOX-1 低表达患者(p=0.047)。此外,高血清 LOX-1 水平组的白细胞计数、C 反应蛋白水平、中性粒细胞/淋巴细胞比值和单核细胞/淋巴细胞比值等炎症因子明显较高。

结论

血清 LOX-1 可能是结直肠癌不良预后的有用标志物。

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