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细胞周期蛋白依赖性激酶亚单位 2(CKS2)作为 I-III 期浸润性非黏液性肺腺癌的预后标志物及其对药物敏感性的影响。

Cyclin-Dependent Kinase Subunit 2 (CKS2) as a Prognostic Marker for Stages I-III Invasive Non-Mucinous Lung Adenocarcinoma and Its Role in Affecting Drug Sensitivity.

机构信息

Department of Pathology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou 450014, China.

Academy of Medical Sciences, Zhengzhou University, Zhengzhou 450001, China.

出版信息

Cells. 2022 Aug 22;11(16):2611. doi: 10.3390/cells11162611.

DOI:10.3390/cells11162611
PMID:36010686
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9406629/
Abstract

With the aim of improving the prognosis of patients with lung adenocarcinoma (LUAD), we identified the biomarker related to the sensitivity of patients to chemotherapy drugs and explored the potential mechanisms. As a cell cycle-related protein, CKS2 has an essential role to play in tumor progression and prognosis. CKS2 expression was measured using TCGA RNA-sequencing data and immunohistochemistry. The sensitivity data of tumor cells to chemotherapeutic drugs for lung cancer was acquired from the Cancer Therapeutics Response Portal (CTRP) database. A range of bioinformatics methods was used to explore the mechanisms of CKS2 upregulation. The biological functions of CKS2 were predicted using GO and KEGG enrichment analysis, as well as GSEA. CKS2 expression was up-regulated in stages I-III invasive non-mucinous lung adenocarcinoma and varied significantly between various histological subtypes. High CKS2 expression worsened the prognosis of patients. The CKS2 expression level was linked to the sensitivity of LUAD cells to carboplatin and paclitaxel. CKS2 upregulation was associated with the immune microenvironment, mRNA methylation, and competing endogenous RNAs (ceRNAs). CKS2 can serve as a diagnostic and prognostic biomarker for stages I-III invasive non-mucinous lung adenocarcinoma and modulate the effect of paclitaxel and carboplatin by regulating microtubule binding and influencing carboplatin binding to DNA.

摘要

为了改善肺腺癌(LUAD)患者的预后,我们鉴定了与患者对化疗药物敏感性相关的生物标志物,并探讨了潜在的机制。作为细胞周期相关蛋白,CKS2 在肿瘤进展和预后中起着至关重要的作用。使用 TCGA RNA-seq 数据和免疫组织化学来测量 CKS2 的表达。从癌症治疗反应门户(CTRP)数据库中获取肿瘤细胞对肺癌化疗药物的敏感性数据。使用一系列生物信息学方法来探索 CKS2 上调的机制。使用 GO 和 KEGG 富集分析以及 GSEA 预测 CKS2 的生物学功能。CKS2 在 I-III 期浸润性非黏液性肺腺癌中表达上调,并且在各种组织学亚型之间存在显著差异。高 CKS2 表达使患者的预后恶化。CKS2 的表达水平与 LUAD 细胞对卡铂和紫杉醇的敏感性相关。CKS2 的上调与免疫微环境、mRNA 甲基化和竞争性内源性 RNA(ceRNA)有关。CKS2 可以作为 I-III 期浸润性非黏液性肺腺癌的诊断和预后生物标志物,并通过调节微管结合和影响卡铂与 DNA 的结合来调节紫杉醇和卡铂的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7189/9406629/a41b4888433c/cells-11-02611-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7189/9406629/84f1d865dbbd/cells-11-02611-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7189/9406629/ea893a347fc5/cells-11-02611-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7189/9406629/bb285e7c1ecc/cells-11-02611-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7189/9406629/ff6afc2dce05/cells-11-02611-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7189/9406629/a41b4888433c/cells-11-02611-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7189/9406629/84f1d865dbbd/cells-11-02611-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7189/9406629/ea893a347fc5/cells-11-02611-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7189/9406629/bb285e7c1ecc/cells-11-02611-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7189/9406629/ff6afc2dce05/cells-11-02611-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7189/9406629/a41b4888433c/cells-11-02611-g005.jpg

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