Identification and Validation of Serum CST1 as a Diagnostic Marker for Differentiating Early-Stage Non-Small Cell Lung Cancer from Pulmonary Benign Nodules.

Identification and Validation of Serum CST1 as a Diagnostic Marker for Differentiating Early-Stage Non-Small Cell Lung Cancer from Pulmonary Benign Nodules.
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DOI:
10.1177/10732748221104661
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发表时间:
2022-01
期刊:
影响因子:
2.6
通讯作者:
Liu, Wanli
Liu, Wanli
中科院分区:
医学4区
文献类型:
--
作者:
Lai, Yanzhen;Wang, Yu;Wu, Yaxian;Wu, Meng;Xing, Shan;Xie, Ying;Chen, Shulin;Li, Xiaohui;Zhang, Ao;He, Yi;Li, Huilan;Dai, Shuqin;Wang, Junye;Lin, Shudai;Bai, Yunmeng;Du, Hongli;Liu, Wanli

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有效的早期诊断手段是降低非小细胞肺癌(NSCLC)患者死亡率的关键。我们的目的是寻找高性能的血清学标志物,以区分早期非小细胞肺癌患者与良性肺结节患者和健康对照(HC)。Cystatin-SN(CST 1)是CST超家族的半胱氨酸蛋白酶抑制剂,参与炎症和肿瘤发生过程。这是首次探索血清CST 1在NSCLC诊断和预后价值。我们分析了来自癌症基因组图谱和基因表达综合数据库的转录组数据,筛选了NSCLC的生物标志物,并通过ONCOMINE数据库验证了候选标志物。采用ELISA、Western blotting和免疫组化方法检测CST 1在NSCLC细胞系、肿瘤组织和临床队列血清中的表达水平。我们鉴定了3个上调的分泌蛋白编码基因,验证了CST 1在NSCLC肿瘤组织和细胞系中的表达水平,并发现NSCLC患者血清中的CST 1水平(4289 ± 2405)pg/mL,显著高于PBN组(1558 ± 441 pg/mL,P < .0001)和健康对照组(1529 ± 416 pg/mL,P < .0001)。用于区分早期NSCLC与PBN/HC的CST 1、细胞角蛋白19片段(Cyfra 21 -1)和癌胚抗原(CEA)的组合的AUC高达0.914/0.925。血清CST 1水平低的NSCLC患者生存率高。血清CST 1可作为鉴别早期NSCLC与PBN和HC的新的诊断标志物,并可作为NSCLC患者预后的预测指标。
Effective means for early diagnosis are imperative to reduce death rate of non-small cell lung cancer (NSCLC) patients. We aimed to find out high-performance serologic markers to distinguish early-stage NSCLC patients from benign pulmonary nodule patients and healthy controls (HC). Cystatin-SN (CST1) is an active cysteine protease inhibitor of the CST superfamily, involving in the processes of inflammation and tumorigenesis. This is the first exploration of the diagnostic and prognostic values of serum CST1 in NSCLC. We analyzed the transcriptome data from The Cancer Genome Atlas and the Gene Expression Omnibus database, screened biomarkers for NSCLC, and verified the candidate markers via the ONCOMINE database. Then, we performed ELISA, western blotting, and immunohistochemistry analysis to detect the expression levels of CST1 in NSCLC cell lines, tumor tissues, and serum samples of clinical cohorts. We identified 3 up-regulated secreted protein-encoding genes, validated the expression levels of CST1 in NSCLC tumor tissues and cell lines, and found that serum CST1 levels of NSCLC (4289 ± 2405 pg/mL) were significantly higher than those of PBN patients (1558 ± 441 pg/mL, P < .0001) and healthy controls (1529 ± 416 pg/mL, P < .0001). The AUC of the combination of CST1, Cytokeratin 19 fragment (Cyfra21-1), and Carcinoembryonic antigen (CEA) for distinguishing early-stage NSCLC from PBN/HC was as high as .914/0.925. Furthermore, our results suggested that the NSCLC patient with low serum CST1 level had a better survival rate. Serum CST1 may serve as a novel diagnostic marker for differentiating early-stage NSCLC from PBN and HC, and could be used as a prognosis predictor in NSCLC patients.
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