本文已被：浏览 590次 下载 660次
投稿时间：2022-04-29 网络发布日期：2022-11-20
投稿时间：2022-04-29 网络发布日期：2022-11-20
中文摘要: 目的 通过生物信息学数据库观察高迁移率族蛋白B-1（HMGB-1）与临床病理特征、肠道菌群的关系，探讨其影响结直肠癌患者预后是否与肠道菌群失衡有关。方法收集公共基因芯片（GEO）数据库中3个结直肠癌数据集的临床资料，分析其与结直肠癌临床特征及预后的关系。选择河北北方学院附属第一医院2021年5月至11月88例结直肠癌患者，检测其血清标本中HMGB-1的表达，并以最佳截断值为界将标本分为HMGB-1H组和HMGB-1L组，从两组中各选取10例患者粪便进行16S rDNA序列测序。结果 ROC曲线显示，数据库中HMGB-1水平预测结直肠癌预后的曲线下面积（AUC）为0.583，HMGB-1的最佳截断值为10.24 ng/ml。与HMGB-1L相比，HMGB-1H的患者TNM分期较晚，总生存期短，易复发和转移（P<0.05），且高HMGB-1水平及和TNM分期是结直肠癌患者死亡的独立危险因素（P＜0.05）。两组患者的16S rDNA测序结果提示HMGB-1H组与HMGB-1L组的菌群组成有一定的相似性；两两比较，在门水平，HMGB-1H组主要以厚壁菌门为主，而HMGB-1L组主要以变形杆菌门为主。在属水平，HMGB-1L发现普罗威登斯菌属富集。Tax4Fun功能预测显示，两者差异菌群的功能富集多集于DNA损伤修复功能，糖酵解、氨基酸代谢等。结论 HMGB-1的升高与结直肠癌的预后差密切相关。HMGB-1的升高可能导致普罗威登斯菌属的减少而影响结直肠癌的预后，机制与结直肠癌的癌细胞DNA损伤修复及其代谢等有关。
中文关键词: 结直肠癌 高迁移率族蛋白B-1 肠道菌群 普罗威登斯菌属
Abstract:Objective To observe the associations of high mobility group protein B-1 (HMGB-1) with clinicopathological characteristics and intestinal flora based on bioinformatics database system to explore whether its influences on the prognosis of colorectal cancer(CRC) was related to the intestinal flora imbalance. Methods The clinical data of three colorectal cancer tumor datasets obtained from GEO (Gene Expression Omnibus) database were collected to analyze the associations of HMGB-1 with the clinical features and outcome of colorectal cancer. Eighty-eight colorectal cancer patients from the First Affiliated Hospital of Hebei North University from May to November 2021 were enrolled to detect the expression of HMGB-1 in their serum samples, which were divided into high HMGB-1group(HMGB-1H) and low HMGB-1 group(HMGB-1L) with best cutoff value of 10.24ng/ml as the boundary. The stool samples of 10 patients in each group were collected for 16S rDNA sequencing. Results ROC curve showed that AUC of HMGB-1 level was 0.583 at the optimal cutoff value of 10.24ng/ml in predicting CRC prognosis. Compared with the patients in HMGB-1L group, the patients in HMGB-1H group presented with later stage of TNM (P=0.005) and shorter overall survival (P=0.033) and were more prone to recurrence and metastasis of CRC (P=0.005).High HMGB-1 level and advanced TNM stage were the independent risk factors of death in CRC patients (P<0.05).The 16S rDNA sequencing results suggested that the microbial community composition was similar in two groups. Pairwise comparison showed that, at the phylum level, the intestinal flora was dominated by Firmicutes in HMGB-1H group and was mainly Proteobacteria in HMGB-1L group; at the genus level, Providencia was found to be enriched in HMGB-1L group. Functional prediction of Tax4Fun showed that the functional enrichment of different intestinal flora was mainly concentrated in DNA damage repair, glycolysis, amino acid metabolism, and so on. Conclusions The elevation of HMGB-1 may introduce a decrease of Providencia and is closely related to the poor prognosis of colorectal cancer, which is associated with the DNA damage repair and metabolism of colorectal cancer cells.
文章编号： 中图分类号： 文献标志码：A
基金项目:河北省政府资助临床医学优秀人才培养项目计划（4）
附件
| Author Name | Affiliation |
| CHEN An-qi*YUAN Na, ZHAO Wei-wei, HAO Xiao-hui, WANG Cong, LU Xiu-rong, SONG Xiao, ZHANG Zhi-lin | Graduate School of Hebei Northern University, Zhangjiakou, Hebei 075000, China |
引用文本：
陈安祺,原娜,赵威威,等.基于生物信息学数据库探讨高迁移率族蛋白B-1影响结直肠癌预后的机制[J].中国临床研究,2022,35(11):1533-1539.
陈安祺,原娜,赵威威,等.基于生物信息学数据库探讨高迁移率族蛋白B-1影响结直肠癌预后的机制[J].中国临床研究,2022,35(11):1533-1539.