首页|IGF2BP1表达水平对肺腺癌顺铂耐药性影响的研究

IGF2BP1表达水平对肺腺癌顺铂耐药性影响的研究

The Effect of IGF2BP1 Expression Level on Cisplatin-Resistance in Lung Adenocarcinoma

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作者先前的研究揭示胰岛素样生长因子2 mRNA结合蛋白(IGF2BP1)在肺腺癌(LUAD)中高表达预示不良预后并影响免疫微环境,为了探讨其对LUAD顺铂耐药的影响,利用CTR-DB数据库揭示了 IGF2BP1在肺癌和间皮瘤等肿瘤中与卡铂联合紫杉醇、顺铂联合培美曲塞等药物抵抗相关;TCGA-LUAD转录组数据挖掘显示顺铂耐药组对奥沙利铂也呈现显著耐药.结果显示IGF2BP1表达与顺铂和奥沙利铂敏感性显著负相关,顺铂耐药组和敏感组的差异基因对甘油三酯代谢、氨基酸跨膜运输、加单氧酶活性和脂肪酸反应等生物功能有显著影响.IGF2BP1与46个顺铂耐药差异表达基因显著共表达,预后分析揭示他们中有32个基因影响LUAD患者总体生存率,且28个基因是预后不良因素.体外实验表明敲除IGF2BP1的LUAD细胞对顺铂敏感性上升,进一步抑制肿瘤细胞生长和克隆形成.综上所述,LUAD IGF2BP1表达水平与患者顺铂敏感性显著相关,IGF2BP1共表达基因显著影响患者预后,通过敲除IGF2BP1能显著提高LUAD细胞对顺铂的敏感性,本项研究可能会为LUAD的耐药带来一个新的研究方向.
The authors previous study revealed that high expression of IGF2BP1 in lung adenocarcinoma(LUAD)is associated with poor prognosis and immune microenvironment.In this study,the impact of IGF2BP1 on cisplatin resistance in LUAD was explored.Analysis of the CTR-DB database revealed that IGF2BP1 is associated with resistance to drugs such as carboplatin combined with paclitaxel and cisplatin combined with pemetrexed in lung cancer and mesothelioma,respectively.Data mining of the TCGA-LUAD transcriptome showed that the cisplatin-resistant group also exhibited significant resistance to oxaliplatin.Moreover,IGF2BP1 expres-sion was significantly negatively correlated with cisplatin and oxaliplatin sensitivity.Further analysis of differential genes between the cisplatin-resistant cohort and cisplatin-sensitive cohort identified several genes associated with different biological functions,such as triglyceride metabolism,amino acid transmembrane transport,monooxygenase activity,and response to fatty acid.Among these genes,IGF2BP1 showed significant co-expression with 46 cisplatin-resistant differential expression genes.Prognostic analysis demonstrated that 32 of these genes significantly affected overall survival in LUAD patients,with 28 genes serving as poor prognostic factors.In vitro experiments revealed that knocking out IGF2BP1 in LUAD cells increased their sensitivity to cisplatin,resulting in decreased tumor cell viability and colony formation.In summary,IGF2BP1 expression levels significantly influences cisplatin resistance of LUAD,and its co-expressed genes significantly impact patient prognosis.Targeting IGF2BP1 can significantly increase the sensitivity of LUAD cells to cisplatin,bringing new avenues for research on drug resistance in LUAD.

IGF2BP1cisplatinprognosislung adenocarcinomachemotherapy resistancebiomarkersthe m6A modification

张乐乐、王学全、丁嘉佩、王微、皮文虎、杨海华、郭乐

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宁夏医科大学检验学院临床病原微生物重点实验室,宁夏银川 750004

浙江省台州医院放疗科台州市放射肿瘤学重点实验室,浙江临海 317000

胰岛素样生长因子2 mRNA结合蛋白 顺铂 预后 肺腺癌 化疗耐药 生物标记物 m6A修饰

2021年国家自然科学基金宁夏自然科学基金重点项目浙江省基础公益研究计划项目台州市抗癌协会专项科研基金项目

821604972022AAC02034LGF22H160058TACA-B03

2024

10.19526/j.cnki.1005-8915.20240303

药物生物技术
中国药科大学,中国医药科技出版社,中国药学会

药物生物技术

CSTPCD
影响因子：0.463
ISSN：1005-8915
年,卷(期)：2024.31(3)
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