Underexpression of LINC00173 in TCF3/PBX1-Positive Cases Is Associated With Poor Prognosis in Children With B-Cell Precursor Acute Lymphoblastic Leukemia.
Underexpression of LINC00173 in TCF3/PBX1-Positive Cases Is Associated With Poor Prognosis in Children With B-Cell Precursor Acute Lymphoblastic Leukemia.
复制标题
DOI：
10.3389/fonc.2022.887766
复制
发表时间：
2022
影响因子：
4.7
通讯作者：
中科院分区：
文献类型：
--
作者：
B细胞前体急性淋巴细胞白血病（BCP-ALL）是全球最常见的儿科癌症。尽管治疗方案有所改进，但仍有约20%的病例无法治愈，这突出表明有必要确定新的生物标志物，以改善目前的临床和分子风险分层方案。我们的目的是研究LINC 00173是否是ALL的生物标志物，并探索其在其他人类癌症类型中的表达水平。进行了一项包括墨西哥BCP-ALL儿童的巢式病例对照研究。使用水解探针通过qRT-PCR评价LINC 00173表达。为了验证我们的研究结果，分别从产生有效治疗的治疗适用研究（TARGET）和基因型组织表达（GTEx）库中检索了BCP-ALL和正常组织的RNA-seq表达数据。还通过从癌症基因组图谱（TCGA）下载可用数据来评估实体瘤中的LINC 00173表达。与正常受试者相比，观察到BCP-ALL病例中LINC 00173的较低表达（p < 0.05）。携带TCF 3/PBX 1融合基因的ALL患者与其他BCP-ALL分子亚型相比，LINC 00173的表达较低（p < 0.04）。LINC 00173低表达与复发（HR = 1.946，95%CI = 1.213-3.120）和死亡（HR = 2.073，95%CI = 1.211-3.547）的高风险相关。LINC 00173低表达的TCF 3/PBX 1患者预后最差（DFS：HR = 12.24，95%CI = 5.04-29.71; OS：HR = 11.19，95%CI = 26-32）。TCGA数据分析显示，LINC 00173的低表达也与六种新报告的肿瘤类型的临床结局不良相关。我们的研究结果表明，LINC 00173是BCP-ALL和其他类型癌症预后不良的生物标志物。我们观察到LINC 00173和TCF 3/PBX 1的表达与BCP-ALL的复发和死亡风险之间的相关性，在TCF 3/PBX 1阳性病例中显示LINC 00173低表达。实验研究需要提供深入了解LINC 00173和TCF 3/PBX的关系。
B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is the most frequent pediatric cancer worldwide. Despite improvements in treatment regimens, approximately 20% of the cases cannot be cured, highlighting the necessity for identifying new biomarkers to improve the current clinical and molecular risk stratification schemes. We aimed to investigate whether LINC00173 is a biomarker in ALL and to explore its expression level in other human cancer types. A nested case–control study including Mexican children with BCP-ALL was conducted. LINC00173 expression was evaluated by qRT-PCR using hydrolysis probes. To validate our findings, RNA-seq expression data from BCP-ALL and normal tissues were retrieved from Therapeutically Applicable Research to Generate Effective Treatments (TARGET) and Genotype-Tissue Expression (GTEx) repositories, respectively. LINC00173 expression was also evaluated in solid tumors by downloading available data from The Cancer Genome Atlas (TCGA). A lower expression of LINC00173 in BCP-ALL cases compared to normal subjects was observed (p < 0.05). ALL patients who carry the TCF3/PBX1 fusion gene displayed lower expression of LINC00173 in contrast to other BCP-ALL molecular subtypes (p < 0.04). LINC00173 underexpression was associated with a high risk to relapse (HR = 1.946, 95% CI = 1.213–3.120) and die (HR = 2.073, 95% CI = 1.211–3.547). Patients with TCF3/PBX1 and underexpression of LINC00173 had the worst prognosis (DFS: HR = 12.24, 95% CI = 5.04–29.71; OS: HR = 11.19, 95% CI = 26–32). TCGA data analysis revealed that underexpression of LINC00173 is also associated with poor clinical outcomes in six new reported tumor types. Our findings suggest that LINC00173 is a biomarker of poor prognosis in BCP-ALL and other types of cancer. We observed an association between the expression of LINC00173 and TCF3/PBX1 and the risk to relapse and die in BCP-ALL, which is worse in TCF3/PBX1-positive cases displaying underexpression of LINC00173. Experimental studies are needed to provide insight into the LINC00173 and TCF3/PBX relationship.
登录
查看更多内容
影响因子：
7.3
作者：
Gao J;Aksoy BA;Dogrusoz U;Dresdner G;Gross B;Sumer SO;Sun Y;Jacobsen A;Sinha R;Larsson E;Cerami E;Sander C;Schultz N
通讯作者：
Schultz N
影响因子：
5
作者：
Han Z;Zhuang X;Yang B;Jin L;Hong P;Xue J;Chen S;Tian Z
通讯作者：
Tian Z
影响因子：
30.5
作者：
Casero D;Sandoval S;Seet CS;Scholes J;Zhu Y;Ha VL;Luong A;Parekh C;Crooks GM
通讯作者：
Crooks GM
影响因子：
3.3
作者：
Du, Qinghua;Liu, Jin;Wu, Jun
通讯作者：
Wu, Jun
影响因子：
7.5
作者：
Fan, Huijie;Yuan, Jing;Li, Xingya
通讯作者：
Li, Xingya