一种用于克服非小细胞肺癌治疗中抗原异质性的多靶向 CAR-T 细胞平台
A Multi-Targeting Chimeric Antigen Receptor-T Cell Platform to Overcome Antigen Heterogeneity in the Treatment of Non-Small Cell Lung Cancer.
这些发现支持采用多靶点CAR-T 策略来应对NSCLC及可能其他实体瘤中的抗原异质性。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Prognostic Implication and Immunological Role of PSMD2 in Lung Adenocarcinoma.
Prognostic Implication and Immunological Role of PSMD2 in Lung Adenocarcinoma.
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尽管既往研究报告26S蛋白酶体非ATP酶调节亚基2(PSMD2)参与多种人类癌症,但其在肺腺癌中的临床意义和功能仍不清楚。本研究探讨了PSMD2在肺腺癌中的预后和免疫学作用。
通过癌症基因组图谱(TCGA)分析PSMD2表达,并使用UALCAN进行验证。利用PrognoScan和Kaplan-Meier曲线评估PSMD2对生存的影响。通过cBioPortal数据库识别PSMD2的突变特征。进行功能富集分析以确定PSMD2相关功能。使用癌症单细胞状态图谱(CancerSEA)在单细胞分辨率下探索PSMD2的癌症功能状态。进行PSMD2相关免疫浸润分析。使用肿瘤-免疫系统相互作用数据库(TISIDB)验证PSMD2表达与TIL(肿瘤浸润淋巴细胞)(TILs)之间的相关性。
PSMD2的mRNA和蛋白表达在肺腺癌中均显著升高。PSMD2高表达与高T分期(p = 0.014)、淋巴结转移(p < 0.001)和TNM分期(p = 0.005)显著相关。Kaplan-Meier曲线表明,PSMD2高表达与较差的总生存期(38.2 vs. 59.7个月,p < 0.001)和疾病特异性生存期(59.9个月 vs. 未达到,p = 0.004)相关。多因素分析提示PSMD2是总生存期较差的独立生物标志物(HR 1.471,95%CI,1.024-2.114,p = 0.037)。PSMD2在肺腺癌中具有14%的高突变频率。PSMD2的基因突变也与肺腺癌较差的总生存期、疾病特异性生存期和无进展生存期相关。功能富集分析提示PSMD2表达参与细胞周期、RNA转运和细胞衰老。CancerSEA分析表明PSMD2表达与细胞周期、DNA损伤和DNA修复呈正相关。免疫浸润分析提示PSMD2表达与免疫细胞浸润水平及TILs丰度相关。
PSMD2上调与肺腺癌不良预后和免疫浸润水平显著相关。我们的发现提示PSMD2是肺腺癌不良预后的潜在生物标志物和免疫治疗靶点。
Background: Although previous studies reported that 26S proteasome non-ATPase regulatory subunit 2 ( PSMD2 ) is involved in many human cancers.
However, its clinical significance and function in lung adenocarcinoma remain unclear.
Here, we examined the prognostic and immunological role of PSMD2 in lung adenocarcinoma. Methods: The Cancer Genome Atlas (TCGA) was conducted to analyze PSMD2 expression and verified using UALCAN. PrognoScan and Kaplan-Meier curves were utilized to assess the effect of PSMD2 on survival. cBioPortal database was conducted to identify the mutation characteristics of PSMD2 . Functional enrichment was performed to determine PSMD2 -related function. Cancer Single-cell State Atlas (CancerSEA) was used to explore the cancer functional status of PSMD2 at single-cell resolution. PSMD2- related immune infiltration analysis was conducted. Tumor-Immune system interaction database (TISIDB) was performed to verify the correlation between PSMD2 expression and tumor-infiltrating lymphocytes (TILs). Results: Both mRNA and protein expression of PSMD2 were significantly elevated in lung adenocarcinoma. High expression of PSMD2 was significantly correlated with high T stage ( p = 0. 014), lymph node metastases ( p < 0. 001), and TNM stage p = 0. 005).
Kaplan-Meier curves indicated that high expression of PSMD2 was correlated with poor overall survival (38. 2 vs. 59. 7 months, p < 0. 001) and disease-specific survival (59. 9 months vs. not available, p = 0. 004). Multivariate analysis suggested that PSMD2 was an independent biomarker for poor overall survival (HR 1. 471, 95%CI, 1. 024-2. 114, p = 0. 037). PSMD2 had a high mutation frequency of 14% in lung adenocarcinoma. The genetic mutation of PSMD2 was also correlated with poor overall survival, disease-specific survival, and progression-free survival in lung adenocarcinoma.
Functional enrichment suggested PSMD2 expression was involved in the cell cycle, RNA transport, and cellular senescence. CancerSEA analysis indicated PSMD2 expression was positively correlated with cell cycle, DNA damage, and DNA repair. Immune infiltration analysis suggested that PSMD2 expression was correlated with immune cell infiltration levels and abundance of TILs. Conclusion: The upregulation of PSMD2 is significantly correlated with poor prognosis and immune infiltration levels in lung adenocarcinoma.
Our findings suggest that PSMD2 is a potential biomarker for poor prognosis and immune therapeutic target in lung adenocarcinoma.
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