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C-FOS/C-JUN转录因子共表达在非小细胞肺癌中的影响

Impact of C-FOS/C-JUN Transcriptional Factors Co-Expression in Non-small Cell Lung Carcinoma.

作者信息

Manios Konstantinos, Chrysovergis Aristeidis, Papanikolaou Vasileios, Tsiambas Evangelos, Adamopoulou Maria, Stamatelopoulos Athanasios, Vachlas Κonstantinos, Papouliakos Sotirios, Pantos Pavlos, Agrogiannis George, Lazaris Andreas C, Kyrodimos Efthymios, Tomos Periklis, Kavantzas Nikolaos

机构信息

Department of Thoracic Surgery, Sotiria Hospital, Athens, Greece.

Department of Otolaryngology, Elpis Hospital, National and Kapodistrian University of Athens, Athens, Greece.

出版信息

Cancer Diagn Progn. 2025 Jan 3;5(1):15-20. doi: 10.21873/cdp.10406. eCollection 2025 Jan-Feb.

Abstract

BACKGROUND/AIM: Significant transcription factors - including c-Fos (gene locus: 14q24.3) and c-Jun (gene locus: 1p32-p31) - regulate cell homeostasis preventing abnormal signal transduction to nucleus. Their over-activation seems to be associated with an aggressive phenotype in non-small cell lung carcinomas (NSCLCs). In the current study, our aim was to co-analyze c-FOS/c-JUN protein expression in a series of NSCLCs correlating them to the corresponding clinico-pathological features.

MATERIALS AND METHODS

A set of fifty (n=50) paraffin embedded NSCLC tissue sections were selected comprising of adenocarcinomas (n=25) and squamous cell carcinomas (n=25), respectively. Immunocytochemistry (IHC) for the c-FOS/c-JUN markers was implemented. Digital image analysis (DIA) was also performed for evaluating objectively the corresponding immunostaining intensity levels of the examined proteins.

RESULTS

All the examined tissue samples expressed the markers in different protein levels. High staining intensity levels were detected in 34/50 (68%) and 24/50 (48%), respectively. C-FOS over expression was statistically significant correlated to stage (p=0.033), whereas C-JUN over expression was associated with NSCLC histotype (p=0.05) and with maximum tumor diameter (p=0.046).

CONCLUSION

C-FOS/C-JUN co- over activation is observed frequently in NSCLC, playing potentially a central role in the aggressiveness of the malignancy's phenotype (advanced stage, increased metastatic potential). Development and implementation of novel agents that target these transcription factors is a promising approach for applying targeted therapeutic strategies in NSCC patients based on specific genetic signatures and protein profiles.

摘要

背景/目的:重要的转录因子——包括c-Fos(基因座:14q24.3)和c-Jun(基因座:1p32-p31)——调节细胞稳态,防止异常信号转导至细胞核。它们的过度激活似乎与非小细胞肺癌(NSCLC)的侵袭性表型相关。在本研究中,我们的目的是共同分析一系列NSCLC中c-FOS/c-JUN蛋白的表达,并将其与相应的临床病理特征相关联。

材料与方法

选取一组50例石蜡包埋的NSCLC组织切片,分别包括腺癌(n=25)和鳞状细胞癌(n=25)。对c-FOS/c-JUN标志物进行免疫细胞化学(IHC)检测。还进行了数字图像分析(DIA),以客观评估所检测蛋白质的相应免疫染色强度水平。

结果

所有检测的组织样本均以不同的蛋白水平表达这些标志物。分别在34/50(68%)和24/50(48%)中检测到高染色强度水平。c-FOS的过表达与分期在统计学上具有显著相关性(p=0.033),而c-JUN的过表达与NSCLC组织类型(p=0.05)和最大肿瘤直径(p=0.046)相关。

结论

在NSCLC中经常观察到c-FOS/c-JUN的共同过度激活,这可能在恶性肿瘤表型的侵袭性(晚期、转移潜能增加)中起核心作用。开发和应用靶向这些转录因子的新型药物是一种有前景的方法,可基于特定的基因特征和蛋白质谱为NSCC患者应用靶向治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd75/11696338/a16e3127037c/cdp-5-17-g0001.jpg

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