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CLEC3B as a potential diagnostic and prognostic biomarker in lung cancer and association with the immune microenvironment.
Cancer Cell International ( IF 5.8 ) Pub Date : 2020-04-01 , DOI: 10.1186/s12935-020-01183-1
Jiaxing Sun 1, 2 , Tian Xie 1, 2 , Muhammad Jamal 2 , Zhenbo Tu 2 , Xinran Li 3 , Yingjie Wu 4 , Jingyuan Li 2 , Qiuping Zhang 2 , Xiaoxing Huang 1
Affiliation  

Background Lung cancer is the leading cause of cancer-related mortality globally. Discovering effective biomarkers for early diagnosis and prognosis is important to reduce the mortality rate and ensure efficient therapy for lung cancer patients. C-type lectin domain family 3 member B (CLEC3B) has been reported in various cancers, but its correlation with lung cancer remains elusive. Methods The GEO, TCGA and Oncomine databases were analyzed to examine the expression of CLEC3B in lung cancer. The CLEC3B mRNA levels in 15 patient tissue samples were detected by real-time PCR and the CLEC3B protein levels in 34 patient tissue samples were detected by immunohistochemistry. A Chi-square test was performed to analyze the correlation of CLEC3B expression and clinicopathological factors. The diagnostic value of CLEC3B was revealed by receiver operating characteristic (ROC) curves. Univariate and multivariate Cox proportional hazards regression models and Kaplan-Meier plots were used to evaluate the prognostic value of CLEC3B in lung cancer. The TIMER database was used to evaluate the correlation of CLEC3B and immune infiltration. Gene set enrichment analysis revealed tumor-associated biological processes related to CLEC3B. Results CLEC3B is significantly downregulated in lung cancer patients compared with nontumor controls according to database analysis and patient tissue sample detection (p < 0.001). Specifically, CLEC3B is significantly downregulated in stage IA lung cancer patients (p < 0.001) and has a high diagnostic accuracy (area under the receiver operating characteristic curve > 0.9). Moreover, low expression of CLEC3B is related to poor progression-free survival (HR = 0.60, 95% CI 0.49-0.74, p = 8.3e-07) and overall survival (HR = 0.66, 95% CI 0.58-0.75, p = 2.1e-10), indicating it as a risk factor for lung cancer. Multivariate analysis value showed that low expression of CLEC3B may be an independent risk factor for disease-free survival in lung cancer patients (HR = 0.655, 95% CI 0.430-0.996, Cox p = 0.048). In addition, we also investigated the potential role of CLEC3B in tumor-immune interactions and found that CLEC3B might be associated with the immune infiltration and immune activation of lung cancer, especially in squamous cell carcinoma. Conclusions Our findings indicate that CLEC3B expression is downregulated in lung cancer and reveal the diagnostic and prognostic potential of CLEC3B in lung cancer and its potential as an immune-related therapeutic target in lung cancer.

中文翻译:

CLEC3B 作为肺癌的潜在诊断和预后生物标志物并与免疫微环境相关。

背景 肺癌是全球癌症相关死亡的主要原因。发现用于早期诊断和预后的有效生物标志物对于降低死亡率和确保肺癌患者的有效治疗非常重要。C 型凝集素结构域家族 3 成员 B (CLEC3B) 已在各种癌症中得到报道,但其与肺癌的相关性仍然难以捉摸。方法分析GEO、TCGA和Oncomine数据库,检测CLEC3B在肺癌组织中的表达。实时荧光定量PCR检测15例患者组织样本中CLEC3B mRNA水平,免疫组化检测34例患者组织样本中CLEC3B蛋白水平。采用卡方检验分析CLEC3B表达与临床病理因素的相关性。受试者工作特征(ROC)曲线揭示了 CLEC3B 的诊断价值。单变量和多变量 Cox 比例风险回归模型和 Kaplan-Meier 图用于评估 CLEC3B 在肺癌中的预后价值。TIMER数据库用于评估CLEC3B与免疫浸润的相关性。基因集富集分析揭示了与 CLEC3B 相关的肿瘤相关生物学过程。结果 根据数据库分析和患者组织样本检测,与非肿瘤对照相比,肺癌患者的 CLEC3B 显着下调(p < 0.001)。具体而言,CLEC3B 在 IA 期肺癌患者中显着下调(p < 0.001)并且具有较高的诊断准确性(受试者工作特征曲线下面积 > 0.9)。而且,CLEC3B 的低表达与较差的无进展生存期(HR = 0.60, 95% CI 0.49-0.74, p = 8.3e-07)和总生存期(HR = 0.66, 95% CI 0.58-0.75, p = 2.1e)有关-10),表明它是肺癌的危险因素。多因素分析值显示CLEC3B低表达可能是肺癌患者无病生存的独立危险因素(HR = 0.655, 95% CI 0.430-0.996, Cox p = 0.048)。此外,我们还研究了CLEC3B在肿瘤-免疫相互作用中的潜在作用,发现CLEC3B可能与肺癌的免疫浸润和免疫激活有关,尤其是在鳞状细胞癌中。
更新日期:2020-04-22
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