LncRNA-mRNA Co-Expression Analysis Identifies AL133346.1/CCN2 as Biomarkers in Pediatric B-Cell Acute Lymphoblastic Leukemia.
LncRNA-mRNA Co-Expression Analysis Identifies AL133346.1/CCN2 as Biomarkers in Pediatric B-Cell Acute Lymphoblastic Leukemia.
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LncRNA-mRNA共表达分析作为儿科B细胞急性淋巴细胞白血病的生物标志物的MANUAL 133346.1/CCN 2。
DOI：
10.3390/cancers12123803
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发表时间：
2020-12-17
期刊：
影响因子：
5.2
通讯作者：
Medina PP
中科院分区：
文献类型：
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作者：
Cuadros M;García DJ;Andrades A;Arenas AM;Coira IF;Baliñas-Gavira C;Peinado P;Rodríguez MI;Álvarez-Pérez JC;Ruiz-Cabello F;Camós M;Jiménez-Velasco A;Medina PP
非编码rna的失调已经在许多类型的癌症中被描述，并且它与致癌或肿瘤抑制活性有关。然而，临床相关的非编码rna在儿童b细胞急性淋巴细胞白血病中的特征仍然知之甚少。在对儿童b细胞急性淋巴细胞白血病特征的长链非编码RNA的研究中，我们发现与健康骨髓相比，长链非编码RNA AL133346.1和邻近的蛋白编码mRNA （CCN2）在白血病样本中显着过表达。生存分析显示，CCN2高表达患者预后明显较好。这些数据表明，AL133346.1/CCN2可用于区分白血病亚型，CCN2表达可预测儿童b细胞急性淋巴细胞白血病患者的预后。小儿急性b细胞淋巴细胞白血病（B-ALL）是一种异质性和侵袭性的肿瘤，需要新的靶向治疗。长链非编码rna最近成为临床上有希望的疾病特异性生物标志物。在这里，我们通过比较肿瘤和非肿瘤样本的转录组特征来鉴定儿童b - all特异性lncrna和相关mrna。我们确定了48个在儿童B-ALL和健康骨髓样本之间差异表达的lncrna。最相关的lncRNA/mRNA对是AL133346.1/CCN2（以前称为RP11-69I8.3/CTGF），其表达在B-ALL样本中呈正相关且升高。它们的差异表达模式和强相关性在外部B-ALL数据集中得到了验证（治疗适用研究产生有效治疗，癌细胞系百科全书）。生存曲线分析显示，CCN2“高”表达患者的总生存率高于“低”表达患者（p = 0.042），该基因可能是儿童B-ALL的独立预后生物标志物。这些发现首次详细描述了lncRNA在儿童B-ALL中的表达谱，并表明这些潜在的生物标志物可能有助于白血病亚型的分类，CCN2表达可以预测儿童b细胞急性淋巴细胞白血病患者的生存结果。
Dysregulation of noncoding RNAs has been described in numerous types of cancers and it has been associated with oncogenic or tumor suppressor activities. However, the signature of clinically relevant noncoding RNAs in pediatric B-cell acute lymphoblastic leukemia is still poorly understood. In a search for long non-coding RNAs that characterize pediatric B-cell acute lymphoblastic leukemia, we found that the long non-coding RNA AL133346.1 and a neighbouring protein-coding mRNA (CCN2) were significantly over-expressed in leukemia samples compared to healthy bone marrow. Survival analysis showed that patients with high CCN2 expression had a significantly better prognosis. These data suggest that AL133346.1/CCN2 could be useful for discriminating subtypes of leukemia and that CCN2 expression could predict the prognosis of pediatric patients with B-cell acute lymphoblastic leukemia. Pediatric acute B-cell lymphoblastic leukemia (B-ALL) constitutes a heterogeneous and aggressive neoplasia in which new targeted therapies are required. Long non-coding RNAs have recently emerged as promising disease-specific biomarkers for the clinic. Here, we identified pediatric B-ALL-specific lncRNAs and associated mRNAs by comparing the transcriptomic signatures of tumoral and non-tumoral samples. We identified 48 lncRNAs that were differentially expressed between pediatric B-ALL and healthy bone marrow samples. The most relevant lncRNA/mRNA pair was AL133346.1/CCN2 (previously known as RP11-69I8.3/CTGF), whose expression was positively correlated and increased in B-ALL samples. Their differential expression pattern and their strong correlation were validated in external B-ALL datasets (Therapeutically Applicable Research to Generate Effective Treatments, Cancer Cell Line Encyclopedia). Survival curve analysis demonstrated that patients with “high” expression levels of CCN2 had higher overall survival than those with “low” levels (p = 0.042), and this gene might be an independent prognostic biomarker in pediatric B-ALL. These findings provide one of the first detailed descriptions of lncRNA expression profiles in pediatric B-ALL and indicate that these potential biomarkers could help in the classification of leukemia subtypes and that CCN2 expression could predict the survival outcome of pediatric B-cell acute lymphoblastic leukemia patients.
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影响因子：
14.9
作者：
Kuleshov MV;Jones MR;Rouillard AD;Fernandez NF;Duan Q;Wang Z;Koplev S;Jenkins SL;Jagodnik KM;Lachmann A;McDermott MG;Monteiro CD;Gundersen GW;Ma'ayan A
通讯作者：
Ma'ayan A
影响因子：
12.3
作者：
Marchese FP;Raimondi I;Huarte M
通讯作者：
Huarte M
影响因子：
16.6
作者：
Gandhi, Minakshi;Gross, Matthias;Diederichs, Sven
通讯作者：
Diederichs, Sven
影响因子：
16
作者：
Paralkar VR;Taborda CC;Huang P;Yao Y;Kossenkov AV;Prasad R;Luan J;Davies JO;Hughes JR;Hardison RC;Blobel GA;Weiss MJ
通讯作者：
Weiss MJ
影响因子：
--
作者：
Ghazavi F;De Moerloose B;Van Loocke W;Wallaert A;Helsmoortel HH;Ferster A;Bakkus M;Plat G;Delabesse E;Uyttebroeck A;Van Nieuwerburgh F;Deforce D;Van Roy N;Speleman F;Benoit Y;Lammens T;Van Vlierberghe P
通讯作者：
Van Vlierberghe P