A Five-LLPS Gene Risk Score Prognostic Signature Predicts Survival in Hepatocellular Carcinoma.

A Five-LLPS Gene Risk Score Prognostic Signature Predicts Survival in Hepatocellular Carcinoma.
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五种 LLPS 基因风险评分预后特征可预测肝细胞癌的生存

DOI:
10.1155/2023/7299276
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发表时间:
2023
影响因子:
2.9
通讯作者:
Lu, Quqin
Lu, Quqin
中科院分区:
生物学4区
文献类型:
--
作者:
Lai, Wenwen;Li, Defu;Ge, Qiong;Yan, Yehong;Luo, Shiwen;Lu, Quqin

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以肝细胞癌(HCC)为主的原发性肝癌是最常见的癌症类型之一,也是2020年癌症死亡的第三大原因。已有研究表明,液-液相分离(LLPS)在包括肝癌在内的多种肿瘤的发生、发展中起着重要作用,但其对患者预后的影响尚不清楚。有必要探讨LLPS基因对预后的影响,以准确预测肝癌患者的预后,并确定相关的靶向治疗部位。 使用癌症基因组图谱数据集和PhaSepDB数据集,我们确定了与HCC患者总生存期(OS)相关的LLPS基因。我们应用最小绝对收缩和选择算子(LASSO)考克斯惩罚回归分析来选择用于风险评分预后标志的最佳基因。然后,我们分析了验证数据集,并评估了风险评分预后特征的有效性。最后,我们进行了定量实时PCR实验以验证预后标记中的基因。 我们鉴定了43个与HCC患者OS相关的差异表达LLPS基因。选择这些基因中的五个(BMX、FYN、KPNA 2、PFKFB 4和SPP 1)以产生预后风险评分特征。在训练数据集和验证数据集中,低风险组患者的OS均优于高风险组患者。我们发现BMX和FYN在HCC肿瘤组织中的表达水平较低,而KPNA 2,PFKFB 4和SPP 1在HCC肿瘤组织中的表达水平较高。验证表明,5-LLPS基因风险评分特征具有预测HCC患者OS的能力。 我们的研究构建了一个五LLPS基因风险评分签名,可以作为一个有效和方便的预后工具。这五个基因可能成为肝癌治疗的潜在靶点。
Primary liver cancer, dominated by hepatocellular carcinoma (HCC), is one of the most common cancer types and the third leading cause of cancer death in 2020. Previous studies have shown that liquid–liquid phase separation (LLPS) plays an important role in the occurrence and development of cancer including HCC, but its influence on the patient prognosis is still unknown. It is necessary to explore the effect of LLPS genes on prognosis to accurately forecast the prognosis of HCC patients and identify relevant targeted therapeutic sites. Using The Cancer Genome Atlas dataset and PhaSepDB dataset, we identified LLPS genes linked to the overall survival (OS) of HCC patients. We applied Least Absolute Shrinkage and Selection Operator (LASSO) Cox penalized regression analysis to choose the best genes for the risk score prognostic signature. We then analysed the validation dataset and evaluated the effectiveness of the risk score prognostic signature. Finally, we performed quantitative real-time PCR experiments to validate the genes in the prognostic signature. We identified 43 differentially expressed LLPS genes that were associated with the OS of HCC patients. Five of these genes (BMX, FYN, KPNA2, PFKFB4, and SPP1) were selected to generate a prognostic risk score signature. Patients in the low-risk group were associated with better OS than those in the high-risk group in both the training dataset and the validation dataset. We found that BMX and FYN had lower expression levels in HCC tumour tissues, whereas KPNA2, PFKFB4, and SPP1 had higher expression levels in HCC tumour tissues. The validation demonstrated that the five-LLPS gene risk score signature has the capability of predicting the OS of HCC patients. Our study constructed a five-LLPS gene risk score signature that can be applied as an effective and convenient prognostic tool. These five genes might serve as potential targets for therapy and the treatment of HCC.
DOI: 10.1158/0008-5472.can-17-3615
发表时间: 2018-09-15
期刊: Cancer research
影响因子: 11.2
作者:
Chen S;Cai C;Sowalsky AG;Ye H;Ma F;Yuan X;Simon NI;Gray NS;Balk SP
通讯作者: Balk SP
DOI: 10.1093/jnen/nlz067
发表时间: 2019-09-01
影响因子: 3.2
作者:
Kessler, Renate;Fleischer, Michael;Eschrich, Klaus
通讯作者: Eschrich, Klaus
DOI: 10.5005/jp-journals-10018-1258
发表时间: 2018-01
期刊: Euroasian journal of hepato-gastroenterology
影响因子: --
作者:
Noor-E-Alam SM
通讯作者: Noor-E-Alam SM
DOI: 10.1126/science.aau5721
发表时间: 2019-03-08
期刊: SCIENCE
影响因子: 56.9
作者:
Huang, William Y. C.;Alvarez, Steven;Groves, Jay T.
通讯作者: Groves, Jay T.
DOI: 10.1002/jso.25078
发表时间: 2018-06-15
影响因子: 2.5
作者:
Choe, Eun K.;Yi, Jin W.;Park, Kyu J.
通讯作者: Park, Kyu J.