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CCND2 是肺腺癌的预后生物标志物,并与免疫浸润相关

英文原题:CCND2 is a prognostic biomarker and correlates with immune infiltration in lung adenocarcinoma.

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CCND2 is a prognostic biomarker and correlates with immune infiltration in lung adenocarcinoma.

PubMed 2024/03/20(内容时间) Transl Cancer Res Q3 · IF 2.1(JCR 2025)

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研究概要

CCND2 可作为参与 LUAD 免疫浸润的新型预后生物标志物,从而为 LUAD 提供新的预防和治疗选择。

研究思路结论见上方概要

CCND2表达影响癌细胞的生长和增殖,并在肿瘤免疫反应中发挥关键作用。然而,很少有研究关注CCND2与肺腺癌(LUAD)在预后和肿瘤免疫浸润方面的相关性。

从癌症基因组图谱(TCGA)数据库中筛选出原始LUAD病例数据。使用R软件,我们分析了LUAD与邻近正常组织之间CCND2的差异表达。进行Kaplan-Meier分析以确定CCND2表达与LUAD患者总生存期之间的关系,并进行Cox回归分析以确定LUAD的独立预后风险因素。使用TIMER(肿瘤免疫估计资源)和CIBERSORTx(通过估计已知RNA转录本的相对子集进行细胞类型鉴定)数据库,研究了CCND2表达与LUAD免疫浸润之间的联系。

CCND2在LUAD中的表达水平显著低于癌旁正常组织[校正P<0.05,log2 fold change (FC) =-1.33]。CCND2低表达的LUAD患者总生存期较短(P=0.046),CCND2是LUAD的独立预后危险因素[风险比(HR):0.77,P=0.049]。在LUAD患者中,CCND2表达与B细胞(r=0.159,P=4.00e-04)、CD8 + T细胞(r=0.287,P=7.88e-11)、CD4 + T细胞(r=0.301,P=8.14e-12)、巨噬细胞(r=0.128,P=4.57e-03)、中性粒细胞(r=0.373,P=1.07e-17)和髓系树突状细胞(r=0.284,P=1.43e-10)的水平呈正相关。B细胞和巨噬细胞的水平与LUAD患者的总生存期显著相关。CIBERSORTx显示,低CCND2表达组中初始B细胞、静息树突状细胞和M1型巨噬细胞的比例较高(P<0.05);而M1型巨噬细胞、活化自然杀伤(NK)细胞和静息CD4 + 记忆细胞较低(P<0.05)。

展开英文摘要原文

CCND2 expression influences the growth and proliferation of cancer cells and plays a crucial role in immune response of tumor. However, few studies focused on the correlation between CCND2 and lung adenocarcinoma (LUAD) in terms of prognosis and tumor immune infiltration.

Original LUAD case data were screened from The Cancer Genome Atlas (TCGA) database. Using R software, we analyzed differently expressed CCND2 between LUAD and adjacent normal tissues. Kaplan-Meier analysis was conducted to determine the relationship between CCND2 expression and the overall survival of LUAD patients, and Cox regression analysis was performed to identify the independently prognostic risk factors for LUAD. Using TIMER (Tumor Immune Estimation Resource) and CIBERSORTx (Cell-type Identification by Estimating Relative Subsets of known RNA Transcripts) databases, the connection between CCND2 expression and LUAD immune infiltration was investigated.

The level of CCND2 was significantly lower in LUAD than in adjacent normal tissues [adjusted P<0.05 and log2 fold change (FC) =-1.33]. LUAD patients who expressed lower CCND2 had a shorter overall survival (P=0.046) and CCND2 was an independently prognostic risk factor for LUAD [hazard ratio (HR): 0.77, P=0.049]. In LUAD patients, CCND2 expression was positively associated with the levels of B cells (r=0.159, P=4.00e-04), CD8 + T cells (r=0.287, P=7.88e-11), CD4 + T cells (r=0.301, P=8.14e-12), macrophages (r=0.128, P=4.57e-03), neutrophils (r=0.373, P=1.07e-17), and myeloid dendritic cells (r=0.284, P=1.43e-10). The levels of B cells and macrophages had significantly association with the overall survival of LUAD patients. CIBERSORTx showed that the proportions of naive B cells, resting dendritic cells, and macrophages M1 were higher in the low CCND2 expression group (P<0.05); whereas macrophages M1, activated natural killer (NK) cells, and resting CD4 + memory cells were lower (P<0.05).

CCND2 can be exploited as a novel prognostic biomarker involved in immune infiltration of LUAD, hence providing new preventative and therapeutic options for LUAD.

论文信息

作者
Jia E、Shi X、Xue J
第一作者单位
Department of Gastroenterology, China-Japan Union Hospital of Jilin University, Changchun, China.China
通讯作者单位
Department of Thoracic Surgery, China-Japan Union Hospital of Jilin University, Changchun, China.China
期刊
Translational cancer research2024 Mar 31
原文标识
PubMed 38617521 · DOI 10.21037/tcr-23-1863