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An investigation into the molecular basis of cancer comorbidities in coronavirus infection.
FEBS Open Bio ( IF 2.6 ) Pub Date : 2020-09-24 , DOI: 10.1002/2211-5463.12984
Antonio Facchiano 1 , Francesco Facchiano 2 , Angelo Facchiano 3
Affiliation  

Comorbidities in COVID‐19 patients often worsen clinical conditions and may represent death predictors. Here, the expression of five genes, known to encode coronavirus receptors/interactors (ACE2, TMPRSS2, CLEC4M, DPP4 and TMPRSS11D), was investigated in normal and cancer tissues, and their molecular relationships with clinical comorbidities were investigated. Using expression data from GENT2 databases, we evaluated gene expression in all anatomical districts from 32 normal tissues in 3902 individuals. Functional relationships with body districts were analyzed by chilibot. We performed DisGeNet, genemania and DAVID analyses to identify human diseases associated with these genes. Transcriptomic expression levels were then analyzed in 31 cancer types and healthy controls from approximately 43 000 individuals, using GEPIA2 and GENT2 databases. By performing receiver operating characteristic analysis, the area under the curve (AUC) was used to discriminate healthy from cancer patients. Coronavirus receptors were found to be expressed in several body districts. Moreover, the five genes were found to associate with acute respiratory syndrome, diabetes, cardiovascular diseases and cancer (i.e. the most frequent COVID‐19 comorbidities). Their expression levels were found to be significantly altered in cancer types, including colon, kidney, liver, testis, thyroid and skin cancers (P < 0.0001); AUC > 0.80 suggests that TMPRSS2, CLEC4M and DPP4 are relevant markers of kidney, liver, and thyroid cancer, respectively. The five coronavirus receptors are related to all main COVID‐19 comorbidities and three show significantly different expression in cancer versus control tissues. Further investigation into their role may help in monitoring other comorbidities, as well as for follow‐up of patients who have recovered from SARS‐CoV‐2 infection.

中文翻译:

对冠状病毒感染中癌症合并症的分子基础的研究。

COVID-19患者的合并症通常会使临床状况恶化,并且可能代表死亡预测因素。在这里,研究了五个已知编码冠状病毒受体/相互作用物的基因(ACE2TMPRSS2CLEC4MDPP4TMPRSS11D)在正常和癌症组织中的表达,并研究了它们与临床合并症的分子关系。使用来自GENT2数据库的表达数据,我们评估了3902个个体中32个正常组织在所有解剖区域的基因表达。通过chilibot分析与身体部位的功能关系。我们执行了GeneGeia的DisGeNetDAVID进行分析以鉴定与这些基因有关的人类疾病。然后,使用GEPIA2和GENT2数据库分析了31种癌症类型和约4.3万名健康对照者的转录组表达水平。通过执行接收器工作特征分析,曲线下的面积(AUC)用于区分健康与癌症患者。发现冠状病毒受体在多个身体部位表达。此外,发现这五个基因与急性呼吸系统综合症,糖尿病,心血管疾病和癌症(即最常见的COVID-19合并症)有关。发现它们的表达水平在包括结肠癌,肾癌,肝癌,睾丸癌,甲状腺癌和皮肤癌在内的多种癌症类型中均发生了显着改变(P <0.0001); AUC> 0.80表明TMPRSS2,CLEC4M和DPP4分别是肾癌,肝癌和甲状腺癌的相关标志物。五个冠状病毒受体与所有主要的COVID-19合并症相关,其中三个在癌症组织和对照组织中的表达明显不同。进一步研究其作用可能有助于监测其他合并症,以及对从SARS-CoV-2感染中康复的患者进行随访。
更新日期:2020-11-04
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