Novel prognostic model predicts overall survival in colon cancer based on RNA splicing regulation gene expression.
Novel prognostic model predicts overall survival in colon cancer based on RNA splicing regulation gene expression.
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作者：
结肠癌是全球第三大常见癌症，也是导致癌症相关死亡的第二大原因。据报道，RNA剪接因子失调与结肠癌的发生和发展有关。在这项研究中，我们从癌症基因组图谱（TCGA）数据集和基因表达Omnibus （GEO）数据库中查询结肠癌患者的临床和RNA表达数据。鉴定与结肠癌存活相关的RNA剪接调控基因，并采用Cox回归分析构建风险评分模型。在风险模型中，RNA剪接因子过氧化酶体增殖物激活受体γ共激活因子- 1α (PPARGC1)与良好的生存结果相关，而Cdc2样激酶1（CLK1）、CLK2和a激酶锚定蛋白8样（AKAP8L）与不良的生存结果相关。该风险模型在TCGA队列和其他两个验证队列中均具有较好的临床预后预测效果。在肿瘤微环境（TME）分析中，低危组免疫评分较高，TME相关通路基因表达也较高。我们进一步验证了这4个基因在结肠癌患者邻近非肿瘤组织、肿瘤组织和肝转移组织中的mRNA和蛋白表达水平，结果与生物信息学分析一致。此外，敲低AKAP8L可抑制结肠癌细胞的增殖和迁移。动物实验也表明，敲低AKAP8L在体内可以抑制结肠癌的肿瘤生长。我们建立了基于RNA剪接调控相关基因的结肠癌预后风险模型，揭示了AKAP8L在促进结肠癌进展中的作用。我们从癌症基因组图谱（TCGA）和基因表达图谱（GEO）数据集中查询结肠癌患者的转录组和相应的临床数据，以研究与预后相关的剪接相关特征。本研究建立了基于RNA剪接调控相关基因的结肠癌预后风险模型。
Colon cancer is the third most common cancer and the second leading cause of cancer‐related death worldwide. Dysregulated RNA splicing factors have been reported to be associated with tumorigenesis and development in colon cancer. In this study, we interrogated clinical and RNA expression data of colon cancer patients from The Cancer Genome Atlas (TCGA) dataset and the Gene Expression Omnibus (GEO) database. Genes regulating RNA splicing correlated with survival in colon cancer were identified and a risk score model was constructed using Cox regression analyses. In the risk model, RNA splicing factor peroxisome proliferator‐activated receptor‐γ coactivator‐1α (PPARGC1) is correlated with a good survival outcome, whereas Cdc2‐like kinase 1(CLK1), CLK2, and A‐kinase anchor protein 8‐like (AKAP8L) with a bad survival outcome. The risk model has a good performance for clinical prognostic prediction both in the TCGA cohort and the other two validation cohorts. In the tumor microenvironment (TME) analysis, the immune score was higher in the low‐risk group, and TME‐related pathway gene expression was also higher in low‐risk group. We further verified the mRNA and protein expression levels of these four genes in the adjacent nontumor, tumor, and liver metastasis tissues of colon cancer patients, which were consistent with bioinformatics analysis. In addition, knockdown of AKAP8L can suppress the proliferation and migration of colon cancer cells. Animal studies have also shown that AKAP8L knockdown can inhibit tumor growth in colon cancer in vivo. We established a prognostic risk model for colon cancer based on genes related to RNA splicing regulation and uncovered the role of AKAP8L in promoting colon cancer progression. we interrogated transcriptome and the corresponding clinical data of colon cancer patients from the The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) dataset to investigate prognosis associated splicing‐related signature.And our study established a prognostic risk model based on RNA splicing regulation related genes for colon cancer.
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影响因子：
10.5
作者：
Li, Yun;Kao, Gary D.;Lazar, Mitchell A.
通讯作者：
Lazar, Mitchell A.
影响因子：
16.2
作者：
Feng, Rui-Mei;Zong, Yi-Nan;Xu, Rui-Hua
通讯作者：
Xu, Rui-Hua
DOI：
10.1084/jem.20130579
发表时间：
2013-08-26
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Simpson TR;Li F;Montalvo-Ortiz W;Sepulveda MA;Bergerhoff K;Arce F;Roddie C;Henry JY;Yagita H;Wolchok JD;Peggs KS;Ravetch JV;Allison JP;Quezada SA
通讯作者：
Quezada SA
影响因子：
4.3
作者：
D'Errico, Ilenia;Lo Sasso, Giuseppe;Moschetta, Antonio
通讯作者：
Moschetta, Antonio
影响因子：
4
作者：
Bhattacharya, Rahul;Mitra, Tulika;Roy, Sib Sankar
通讯作者：
Roy, Sib Sankar