nav emailalert searchbtn searchbox tablepage yinyongbenwen piczone journalimg journalInfo searchdiv qikanlogo popupnotification

请选择需要下载的pdf数据

正在翻译英文数据 ...
paper paperNew
2024, 06, v.52 77-86
基于数据挖掘的缺氧调控铁死亡参与结肠癌发生机制研究
基金项目(Foundation): 江汉大学校级学生科研项目(2023yb167)
邮箱(Email):
DOI: 10.16389/j.cnki.cn42-1737/n.2024.06.009
摘要:

目的 基于数据挖掘技术,探讨在缺氧条件下铁死亡参与结肠癌的机制。方法 以TCGA-COAD为实验队列,GSE39582为验证队列。根据174个缺氧相关基因和517个铁死亡相关基因,通过Cox和LASSO回归分析构建风险评分预后模型,将数据中所有病患区分为高风险组和低风险组。随后进一步对两个风险组之间的临床和免疫特征进行综合分析,最后进行高低风险组之间的差异基因与结肠癌的GO(BP、MF、CC)和KEGG富集分析。结果 构建了包含9个基因(CDKN2A、FNDC5、ENO3、GSTM1、JDP2、ANGPTL4、ANKZF1、TKTL1、PPARGC1A)的风险评分模型。与高风险组相比,低风险组预后较佳,且高风险组的免疫细胞浸润水平高于低风险组。通过对高低风险评分组之间的差异基因进行GO分析及KEGG通路富集分析显示与MAPK信号通路、Rap1信号通路、趋化因子信号通路等肿瘤及免疫相关通路密切相关。结论 构建了缺氧条件下结合铁死亡的结肠癌患者风险评分模型,可为肿瘤的个体化治疗提供新的思路。

Abstract:

Objective To study the mechanism of ferroptosis involved in colon cancer under hypoxia based on data mining technology. Methods Taking TCGA-COAD as the experimental cohort and GSE39582 as the verification cohort,based on 174 hypoxiarelated genes and 517 ferroptosis-related genes,a risk-scoring prognostic model was constructed by Cox and LASSO regression analysis,and the patients were divided into high-risk and low-risk groups. Then,the clinical and immune characteristics of the two risk groups were further analyzed. Finally,GO(BP,MF,CC) and KEGG enrichment analysis of differential genes between the high and low-risk groups were performed. Results A risk-scoring model containing 9 genes(CDKN2A,FNDC5,ENO3,GSTM1,JDP2,ANGPTL4, ANKZF1, TKTL1, PPARGC1A) was constructed. Compared with the high-risk group,the low-risk group had a better prognosis,and the level of immune cell infiltration in the high-risk group was higher than that in the low-risk group. Through GO analysis and KEGG pathway enrichment analysis,the differential genes between the highlow risk groups were shown to be correlated with the MAPK signaling pathway,Rap1signaling pathway,Chemokine signaling pathway,and other tumor and immune-related pathways. Conclusion The risk-scoring model for colon cancer patients with ferroptosis under hypoxia conditions provides a new idea for individualized tumor treatment.

参考文献

[1]李祎琪,杨健康,王小燕.铁死亡相关基因与结肠癌分型及预后的关系研究[J].基因组学与应用生物学,2022,41(7):1590-1601.

[2] MONJUR A. Colon cancer:a clinician′s perspective in 2019[J]. Gastroenterology Research,2020,13(1):1-10.

[3]姜帆.几种肿瘤微环境响应的多功能纳米复合体系的构建及应用[D].合肥:中国科学技术大学,2022.

[4]谭钦文,杜沅沁,徐健,等.肝癌干细胞的有氧糖酵解特性及其在肿瘤微环境中的适应性机制[J].生命的化学,2023,43(2):187-195.

[5]袁静,王海燕,邢永华,等.基于铁死亡调控的癌症治疗研究进展[J].实用肿瘤杂志,2023,38(1):73-79.

[6] WANG Y,WEI Z,PAN K,et al. The function and mechanism of ferroptosis in cancer[J]. Apoptosis,2020,25(11/12):786-798.

[7] HONG Y,ZHANG L,TIAN X,et al. Identification of immune subtypes of Ph-neg B-ALL with ferroptosis related genes and the potential implementation of Sorafenib[J]. BMC Cancer,2021,21(1):1331.

[8]蔡招聘,管观文,陈佑甲,等. 2003—2022年我国结直肠癌研究的文献计量分析[J].浙江师范大学学报(自然科学版),2024,47(1):46-54.

[9] ZHANG T,SONG X,QIAO J,et al. A novel predictive model for adrenocortical carcinoma based on hypoxia-and ferroptosis-related gene expression[J]. Frontiers in Medicine,2022,9:856606.

[10] WANG D,WEI G,MA J,et al. Identification of the prognostic value of ferroptosis-related gene signature in breast cancer patients[J]. BMC Cancer,2021,21(1):645.

[11] YANG C B,FENG H X,DAI C L. Development and validation of an immune-related prognosis signature associated with hypoxia and ferroptosis in hepatocellular carcinoma[J]. Cancer Med,2022,11(11):2329-2341.

[12] H?NZELMANN S,CASTELO R,GUINNEY J. GSVA:gene set variation analysis for microarray and RNAseq data[J]. BMC Bioinformatics,2013,14:7.

[13]杨纯博.肝细胞癌中缺氧和铁死亡相关的基因预后模型的构建与验证[D].沈阳:中国医科大学,2023.

[14] LIU N Q,DE MARCHI T,TIMMERMANS A M,et al. Ferritin heavy chain in triple negative breast cancer:a favorable prognostic marker that relates to a cluster of differentiation 8 positive(CD8+)effector T-cell response[J]. Mol Cell Proteomic,2014,13(7):1814-1827.

[15] MOU Y,WU J,ZHANG Y,et al. Low expression of ferritinophagyrelated NCOA4gene in relation to unfavorable outcome and defective immune cells infiltration in clear cell renal carcinoma[J]. BMC Cancer,2021,21(1):18.

[16] LIN W,WANG C,LIU G,et al. SLC7A11/xCT in cancer:biological functions and therapeutic implications[J]. Am J Cancer Res,2020,10(10):3106-3126.

[17] YIM M S,HA Y S,KIM I Y,et al. HMOX1 is an important prognostic indicator of nonmuscle invasive bladder cancer recurrence and progression[J]. J Urol,2011,185(2):701-705.

[18] YANG G,WANG H,SUN B. Construction of cuproptosis-associated prognostic signature in colon adenocarcinoma based on bioinformatics and RT-qPCR analysis[J]. Oncol Lett,2023,25(3):91.

基本信息:

DOI:10.16389/j.cnki.cn42-1737/n.2024.06.009

中图分类号:R735.35

引用信息:

[1]杨光,田瑶,谢寒丹.基于数据挖掘的缺氧调控铁死亡参与结肠癌发生机制研究[J].江汉大学学报(自然科学版),2024,52(06):77-86.DOI:10.16389/j.cnki.cn42-1737/n.2024.06.009.

基金信息:

江汉大学校级学生科研项目(2023yb167)

引用

GB/T 7714-2015 格式引文
MLA格式引文
APA格式引文