基因SEZ6L2與結腸癌預后的相關研究
首發時間:2021-06-16
摘要:目的:通過腫瘤基因組圖譜(The Cancer Genome Atlas,TCGA)的基因表達數據和結腸癌臨床病理數據,對基因SEZ6L2進行分析,為結腸癌尋找潛在的預后靶向分子并以此構建預后模型。方法:從TCGA數據庫下載結腸癌基因表達數據以及相應的臨床病理數據,應用Perl和R語言對數據進行整理,并提取基因SEZ6L2的表達量。對基因SEZ6L2進行差異分析、生存分析和臨床相關性分析。然后,刪除刪失值,形成全數據集,構建預后模型并進行Cox分析,以關鍵分子SEZ6L2命名模型,即SEZ6L2模型,并與傳統TNM分期比較預測結腸癌預后的準確性。最后,對基因SEZ6L2進行基因富集分析(Gene Set Enrichment Analysis,GSEA)。結果:基因SEZ6L2在結腸癌組織中表達高于正常組織,有統計學差異;基因SEZ6L2高表達患者生存率比低表達患者低,有統計學差異;基因SEZ6L2高表達患者在臨床分期、T(Tumor,原發腫瘤)分期、N(Node,淋巴結)分期、血管浸潤和淋巴侵襲等臨床特征方面表現出更差的預后,均有統計學意義。構建的SEZ6L2模型中有SEZ6L2、年齡、T分期、M(Metastasis,轉移)分期、臨床分期和血管侵襲等變量。單因素和多因素Cox分析提示SEZ6L2可以獨立反映結腸癌患者預后。SEZ6L2模型的Kaplan-Meier分析顯示,得分高的患者生存率低于得分低的患者,有統計學差異。校準曲線顯示,SEZ6L2模型的預測情況與實際情況相一致。IDI(Integrated Discrimination Improvement,綜合判別改善指數)的計算結果Research on the correlation between SEZ6L2 and the prognosis of colon cancer顯示,SEZ6L2模型在第1年和第3年預測結腸癌預后的準確性高于TNM分期,而在第5年和第10年,其預測準確性與TNM分期相似,即SEZ6L2模型預測短期結腸癌預后的準確性高于傳統TNM分期,而長期的預測準確性相似。DCA(Decision Curve Analysis,決策曲線分析法)的結果與IDI的相一致。GSEA顯示,NOTCH信號通路、VEGF信號通路、GNRH信號通路等在SEZ6L2高表達表型富集。結論:SEZ6L2是結腸癌預后的分子標志物,其高表達提示預后不良;SEZ6L2模型預測短期結腸癌預后的準確性高于傳統TNM分期,可以作為結腸癌短期預后的參考模型。
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Research on the correlation between SEZ6L2 and the prognosis of colon cancer
Abstract:Objective: By using gene expression data and clinicopathological data of colon cancer from the Cancer Genome Atlas (TCGA), gene SEZ6L2 was analyzed to find a potential prognostic molecule for colon cancer based on which a prognostic model were constructed. Methods: The gene expression data and clinical data of colon cancer were downloaded from TCGA databases. The data were organized by Perl and R language, from which the expression of gene SEZ6L2 was extracted. Gene SEZ6L2 was analyzed by differential analysis, survival analysis and clinical correlation analysis. Censored data was deleted to form the complete-case data to construct the prognosis model: SEZ6L2 model, which was compared with traditional TNM stage. Meanwhile, Cox analysis and Gene Set Enrichment Analysis (GSEA) were performed. Results: The expression of SEZ6L2 in tumor tissues was significantly higher than that in normal tissues. Patients with high expression of SEZ6L2 had lower survival rate than that with low expression of SEZ6L2. The patients with high expression of SEZ6L2 showed worse clinical prognostic features such as clinical stage, T stage, N stage, vascular invasion and lymphatic invasion. All results were statistically significant. In SEZ6L2 model, there were SEZ6L2, age, T stage, M stage, clinical stage and vascular invasion. Univariate and multivariate Cox analysis showed that SEZ6L2 could be used as an independent prognostic factor of colon cancer. Kaplan-Meier analysis of the SEZ6L2 model showed that patients with high scores had lower survival rates than those with low scores. The calibration curves showed that the prediction of SEZ6L2 model was consistent with the actual situation. The calculation results of IDI (Integrated Discrimination Improvement) showed that the accuracy of SEZ6L2 model in predicting the prognosis of colon cancer in the first and third year was higher than that of TNM stage, but the same in the 5th and 10th year. In other words, the short-term prognosis prediction of colon cancer by SEZ6L2 model was better than that by traditional TNM stage, but the same in long term. The results of DCA (Decision Curve Analysis) were consistent with that of IDI. GSEA showed that Notch signaling pathway, VEGF signaling pathway, GNRH signaling pathway, etc. were differentially enriched in SEZ6L2 high expression phenotype. Conclusions: SEZ6L2 is a molecular marker for the prognosis of colon cancer. Its high expression indicates poor prognosis. The short-term predictive value of SEZ6L2 model is higher than that of traditional TNM stage. Therefore, SEZ6L2 model can be used as a reference model for short-term prognosis prediction of colon cancer.
Keywords: surgery SEZ6L2 colon cancer TCGA prognosis
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基因SEZ6L2與結腸癌預后的相關研究
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