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Abstract：
Lung adenocarcinoma (LUAD) is the predominant type of non-small lung cancer (NSCLC) with strong invasive ability and poor prognosis. The drug resistance related genes are potentially associated with prognosis of LUAD. Our research aimed to identify the drug resistance related genes and explore their potential prognostic value in LUAD patients. The data used in this study were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Firstly, we screened drug resistance related genes in LUAD by differential gene analysis, univariate Cox regression and drug sensitivity analyses. Subsequently, we constructed a risk score model using LASSO Cox regression analysis, and verified whether the risk score can predict the survival of LUAD patients independent of other factors. Moreover, we explored the immune infiltration of 22 immune cells between high-risk and low-risk patients. Totally 10 drug-resistance positively related genes (PLEK2, TFAP2A, KIF20A, S100P, GDF15, HSPB8, SASH1, WASF3, LAMA3 and TCN1) were identified in LUAD. The risk score model of LUAD constructed with these 10 genes could reliably predict the prognosis of LUAD patients. 18 pathways were significantly activated in high-risk group compared with low-risk group. In addition, the infiltration proportion of multiple immune cells was significantly different between high-risk and low-risk groups, and the proportion of M1 phagocytes was significantly higher in the high-risk group compared with the low-risk group. The drug resistance related genes (PLEK2, TFAP2A, KIF20A, S100P, GDF15, HSPB8, SASH1, WASF3, LAMA3 and TCN1) could predict the prognosis of LUAD patients. Clarifying the roles and mechanisms of these 10 genes in regulating drug resistance in LUAD will help to improve individualized clinical treatment protocols and predict patient sensitivity to treatment.
摘要：
肺腺癌(LUAD)是非小细胞肺癌(NSCLC)的主要类型,侵袭能力强,预后差。耐药相关基因可能与LUAD的预后相关。我们的研究旨在鉴定耐药相关基因，并探讨其在LUAD患者中的潜在预后价值。本研究中使用的数据来自癌症基因组图谱(TCGA)和基因表达综合(GEO)数据库。首先,通过差异基因分析筛选出LUAD耐药相关基因,单变量Cox回归和药物敏感性分析。随后，我们使用LASSOCox回归分析构建了风险评分模型，并验证了风险评分是否可以独立于其他因素预测LUAD患者的生存。此外，我们探讨了高危和低危患者之间22个免疫细胞的免疫浸润情况.共有10个耐药正相关基因(PLEK2、TFAP2A、KIF20A,S100P,在LUAD中鉴定了GDF15，HSPB8，SASH1，WASF3，LAMA3和TCN1）。利用这10个基因构建的LUAD风险评分模型能够可靠地预测LUAD患者的预后。与低危组相比，高危组有18条通路显著激活。此外,多种免疫细胞的浸润比例在高危和低危人群中差异显著,高危组M1吞噬细胞比例明显高于低危组。耐药相关基因(PLEK2、TFAP2A、KIF20A,S100P,GDF15，HSPB8，SASH1，WASF3，LAMA3和TCN1）可以预测LUAD患者的预后。阐明这10个基因在调节LUAD耐药中的作用和机制将有助于改善个体化临床治疗方案和预测患者对治疗的敏感性。
