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多种异常基因在非小细胞肺癌中的预后作用

Prognostic role of multiple abnormal genes in non-small-cell lung cancer.

作者信息

Yan Lu-Da, Yang Liu, Li Na, Wang Meng, Zhang Yan-Hua, Zhou Wen, Yu Zhi-Qiong, Peng Xiao-Chun, Cai Jun

机构信息

Department of Oncology, The First Affiliated Hospital of Yangtze University, Jingzhou 434023, Hubei Province, China.

Department of Pathophysiology, School of Basic Medicine, Health Science Center, Yangtze University, Jingzhou 434023, Hubei Province, China.

出版信息

World J Clin Cases. 2022 Aug 6;10(22):7772-7784. doi: 10.12998/wjcc.v10.i22.7772.

Abstract

BACKGROUND

Non-small-cell lung cancer (NSCLC) has the highest morbidity and mortality rates among all malignant tumor types. Although therapies targeting the mutated genes such as have been used in the clinic for many years, the prognosis remains poor. Therefore, it is necessary to further study the aberrant expression or mutation of non-target genes affecting the survival and prognosis.

AIM

To explore the impact of simultaneous abnormalities of multiple genes on the prognosis and survival of patients.

METHODS

We used R packages to analyze gene expression data and clinical data downloaded from The Cancer Genome Atlas (TCGA) database. We also collected samples from 85 NSCLC patients from the First People's Hospital of Jingzhou City and retrospectively followed the patients. Multivariate Cox regression analysis and survival analysis were performed.

RESULTS

Analysis of gene expression data from TCGA revealed that the overexpression of the following single genes affected overall survival: ( = 0.79), ( = 0.94), ( = 0.49), ( = 0.24), ( = 0.32), and ( = 0.013). However, the probability of multiple genes (, , , and ) affecting survival was 0.025. Retrospective analysis of clinical data revealed that sex (hazard ratio [HR] = 1.29; [95%CI: 0.64-2.62]), age (HR = 1.05; [95%CI: 1.02-1.07]), smoking status (HR = 2.26; [95%CI: 1.16-4.39]), tumor histology (HR = 0.58; [95%CI: 0.30-1.11]), cancer stage (HR = 16.63; [95%CI: 4.8-57.63]), epidermal growth factor receptor () mutation (HR = 1.82; [95%CI: 1.05-3.16]), abundance (HR = 4.95; [95%CI: 0.78-31.36]), and treatment with tyrosine kinase inhibitors (TKIs) (HR = 0.58; [95%CI: 0.43-0.78]) affected patient survival. Co-occurring mutations of , , , and did not significantly affect the overall survival of patients receiving chemotherapy ( = 0.96) but significantly affected the overall survival of patients receiving TKIs ( = 0.045).

CONCLUSION

Co-occurring mutation or overexpression of different genes has different effects on the overall survival and prognosis of NSCLC patients. Combined with TKI treatment, the co-occurring mutation of some genes may have a synergistic effect on the survival and prognosis of NSCLC patients.

摘要

背景

在所有恶性肿瘤类型中,非小细胞肺癌(NSCLC)的发病率和死亡率最高。尽管针对如 等突变基因的疗法已在临床应用多年,但预后仍然很差。因此,有必要进一步研究影响生存和预后的非靶基因的异常表达或突变。

目的

探讨多个基因同时异常对患者预后和生存的影响。

方法

我们使用R软件包分析从癌症基因组图谱(TCGA)数据库下载的基因表达数据和临床数据。我们还收集了荆州市第一人民医院85例NSCLC患者的样本,并对患者进行回顾性随访。进行多变量Cox回归分析和生存分析。

结果

对TCGA基因表达数据的分析显示,以下单个基因的过表达影响总生存期: ( = 0.79), ( = 0.94), ( = 0.49), ( = 0.24), ( = 0.32),以及 ( = 0.013)。然而,多个基因( 、 、 、和 )影响生存的概率为0.025。临床数据的回顾性分析显示,性别(风险比[HR] = 1.29;[95%置信区间:0.64 - 2.62])、年龄(HR = 1.05;[95%置信区间:1.02 - 1.07])、吸烟状况(HR = 2.26;[95%置信区间:1.16 - 4.39])、肿瘤组织学(HR = 0.58;[95%置信区间:0.30 - 1.11])、癌症分期(HR = 16.63;[95%置信区间:4.8 - 57.63])、表皮生长因子受体( )突变(HR = 1.82;[95%置信区间:1.05 - 3.16])、丰度(HR = 4.95;[95%置信区间:0.78 - 31.36])以及酪氨酸激酶抑制剂(TKIs)治疗(HR = 0.58;[95%置信区间:0.43 - 0.78])影响患者生存。 、 、 、和 的共同突变对接受化疗患者的总生存期没有显著影响( = 0.96),但对接受TKIs治疗患者的总生存期有显著影响( = 0.045)。

结论

不同基因的共同突变或过表达对NSCLC患者的总生存期和预后有不同影响。与TKI治疗相结合,某些基因的共同突变可能对NSCLC患者的生存和预后产生协同作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8557/9372825/794619622727/WJCC-10-7772-g001.jpg

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