生物信息学共表达外推法初构食管癌精准化疗生物标志物模型

Preliminary construction of precise chemotherapy biomarker models for esophageal cancer using COXEN method of bioinformatics

目的:用生物信息学共表达外推(以下简称生信COXEN)法初步构建食管癌精准化疗药物(5-氟尿嘧啶、紫杉醇和顺铂)生物标志物模型。方法:本研究使用5种统计学方法(Pearson相关分析、Spearman相关分析、Welch’s t-test、ANCOVA和rank-based ANCOVA)从NCI-60数据库筛选药物敏感性基因,通过COXEN筛选食管鳞状细胞癌患者化疗药物敏感性的生物标志物。利用在线数据库DAVID进行KEGG通路富集分析。结果:筛选出可应用于预测人类食管鳞状细胞癌化疗药物敏感性的生物标志物:5-氟尿嘧啶的生物标志物主要富集在细胞周期G1期和S期(RNA和核糖体的合成、DNA复制)中;顺铂的生物标志物主要与蛋白聚糖、细菌侵袭上皮细胞和白细胞跨内皮迁移有关;紫杉醇的生物标志物主要与局部黏附、小细胞肺癌和HTLV-I感染通路有关。结论:生信COXEN法筛选出可应用于预测人类食管鳞状细胞癌单个化疗药物敏感性的基因,能为将来构建更有转化应用价值的多组合化疗方案预测模型提供研究基础。

OBJECTIVE To preliminarily construct a biomarker model of precise chemotherapeutic drugs(5-fluorouracil, paclitaxel and cisplatin) for esophageal cancer using the COXEN method of bioinformatics.METHODS In this study, five statistical methods(Pearson correlation analysis, Spearman correlation analysis, Welch’s t-test, ANCOVA and rank-based ANCOVA) were used to screen drug sensitivity genes from NCI-60 database, and biomarkers of chemosensitivity in patients with esophageal squamous cell carcinoma were screened by coexpression extrapolation(COXEN). KEGG pathway enrichment analysis was performed using the online database DAVID.RESULTS Biomarkers that could be applied to predict the sensitivity of human esophageal squamous cell carcinoma to chemotherapeutic drugs were selected: biomarkers of 5-fluorouracil were mainly enriched in G1 and S phases of the cell cycle(synthesis of RNA and ribosomes, DNA replication);biomarkers were mainly related to proteoglycans, bacterial invasion of epithelial cells and transendothelial migration of leukocytes;biomarkers of paclitaxel were mainly related to local adhesion, small cell lung cancer and HTLV-I infection pathways.CONCLUSION The COXEN method can select genes that can be used to predict the sensitivity of individual chemotherapeutic drugs in human esophageal squamous cell carcinoma, and provide the research basis for constructing a more valuable prediction model of multi-combination chemotherapy regimens in the future.