Pan-cancer analysis of alternative splicing regulator heterogeneous nuclear ribonucleoproteins (hnRNPs) family and their prognostic potential.
Pan-cancer analysis of alternative splicing regulator heterogeneous nuclear ribonucleoproteins (hnRNPs) family and their prognostic potential.
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DOI：
10.1111/jcmm.15558
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发表时间：
2020-10
影响因子：
5.3
通讯作者：
Guo X
中科院分区：
文献类型：
--
作者：
Li H;Liu J;Shen S;Dai D;Cheng S;Dong X;Sun L;Guo X
异质核核糖核蛋白（hnRNP）作为最重要的选择性剪接调节因子，与肿瘤的发生发展密切相关。然而，对hnRNP在癌症中的全面了解仍然缺乏。基于下一代序列数据，系统分析了33种癌症类型中hnRNP基因的分子改变和临床相关性。hnRNP的表达、突变、拷贝数变异、功能途径、免疫细胞相关性和预后价值在不同癌症类型中进行了研究。HNRNPA 1和HNRNPAB在大多数肿瘤中高表达。HNRNPM、HNRNPUL 1和HNRNPL基因突变频率较高，且大多数hnRNP基因在子宫体子宫内膜癌（UCEC）中突变频率较高。HNRNPA 2B 1在各种癌症类型中表现出广泛的拷贝数扩增。HNRNPs参与了蛋白质分泌、有丝分裂纺锤体、G2/M检查点、DNA修复、IL 6/JAK/STAT 3信号传导和凝血等肿瘤相关通路，其中HNRNPF、HNRNPH 2、HNRNPU和HNRNPUL 1的hnRNP基因更可能参与其中。hnRNP基因与T辅助细胞、NK细胞、CD 8阳性T细胞和中性粒细胞显著相关。大多数hnRNP与肾上腺皮质癌（ACC）、肝细胞癌（LIHC）和肺腺癌（LUAD）的生存率较差相关，而hnRNP预测肾透明细胞癌（KIRC）和胸腺瘤（THYM）的预后较好。KIRC预后分析提示hnRNP基因簇与总生存期显著相关（HR = 0.5，95%CI = 0.35 - 0.73，P = 0.003）。这些发现为今后进一步研究hnRNP在肿瘤发生发展和治疗中的作用提供了新的证据。
As the most critical alternative splicing regulator, heterogeneous nuclear ribonucleoproteins (hnRNPs) have been reported to be implicated in various aspects of cancer. However, the comprehensive understanding of hnRNPs in cancer is still lacking. The molecular alterations and clinical relevance of hnRNP genes were systematically analysed in 33 cancer types based on next‐generation sequence data. The expression, mutation, copy number variation, functional pathways, immune cell correlations and prognostic value of hnRNPs were investigated across different cancer types. HNRNPA1 and HNRNPAB were highly expressed in most tumours. HNRNPM, HNRNPUL1, and HNRNPL showed high mutation frequencies, and most hnRNP genes were frequently mutated in uterine corpus endometrial carcinoma (UCEC). HNRNPA2B1 showed widespread copy number amplification across various cancer types. HNRNPs participated in cancer‐related pathways including protein secretion, mitotic spindle, G2/M checkpoint, DNA repair, IL6/JAK/STAT3 signal and coagulation, of which hnRNP genes of HNRNPF, HNRNPH2, HNRNPU and HNRNPUL1 are more likely to be implicated. Significant correlation of hnRNP genes with T help cells, NK cells, CD8 positive T cells and neutrophils was identified. Most hnRNPs were associated with worse survival of adrenocortical carcinoma (ACC), liver hepatocellular carcinoma (LIHC) and lung adenocarcinoma (LUAD), whereas hnRNPs predicted better prognosis in kidney renal clear cell carcinoma (KIRC) and thymoma (THYM). The prognosis analysis of KIRC suggested that hnRNPs gene cluster was significantly associated with overall survival (HR = 0.5, 95% CI = 0.35‐0.73, P = 0.003). These findings provide novel evidence for further investigation of hnRNPs in the development and therapy of cancer in the future.
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影响因子：
7.4
作者：
Kumar M;Matta A;Masui O;Srivastava G;Kaur J;Thakar A;Shukla NK;RoyChoudhury A;Sharma M;Walfish PG;Michael Siu KW;Chauhan SS;Ralhan R
通讯作者：
Ralhan R
影响因子：
5.6
作者：
Martinez-Montiel N;Rosas-Murrieta NH;Anaya Ruiz M;Monjaraz-Guzman E;Martinez-Contreras R
通讯作者：
Martinez-Contreras R
影响因子：
1.6
作者：
Alsagaby, Suliman A.
通讯作者：
Alsagaby, Suliman A.
影响因子：
4.3
作者：
Rahmutulla, Bahityar;Matsushita, Kazuyuki;Nomura, Fumio
通讯作者：
Nomura, Fumio
DOI：
10.1007/978-0-387-77374-2_8
发表时间：
2007-01-01
期刊：
ALTERNATIVE SPLICING IN THE POSTGENOMIC ERA
影响因子：
--
作者：
Martinez-Contreras, Rebeca;Cloutier, Philippe;Chabot, Benoit
通讯作者：
Chabot, Benoit