CCT3 Facilitates the Malignant Progression of NSCLC and SCLC via PI3 K/AKT-EMT Axis and Emerges as a Novel Serum Diagnostic Biomarker

CCT3通过PI3K/AKT-EMT轴促进非小细胞肺癌和小细胞肺癌的恶性进展,并成为一种新型血清诊断生物标志物。

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作者:Guobin Song,Kexin Han,Lin Xiang,Tian Peng,Hailong Chen,Anqi Tang,Yanan Li,Tianqi Lan,Houqun Ying,Xuexin Cheng

Abstract

IntroductionIdentifying therapeutic targets and early screening biomarkers is essential for improving the prognosis of lung cancer. CCT3 has been linked to tumor progression; however, its role in lung cancer proliferation and invasion, as well as its diagnostic significance remain poorly understood.MethodsCCT3 expression and its clinical correlations in lung cancer were analyzed utilizing data from the TCGA and GEO databases. The impact of CCT3 on cell proliferation, migration, and invasion was evaluated through CCK-8, colony formation, and Transwell assays. Western blotting was employed to assess the regulation of the PI3 K/AKT pathway and markers associate with epithelial-mesenchymal transition (EMT). Serum CCT3 levels in 714 participants were measured via ELISA, with diagnostic efficacy analyzed using receiver operating characteristic (ROC) curve analysis.ResultsCCT3 was over-expressed in lung cancer tissues, which was correlated with the stage of non-small lung cancer (NSCLC). CCT3 promotes cell proliferation, migration, and invasion by activating the PI3 K/AKT pathway and modulating EMT. In vivo, CCT3 knockdown significantly suppressed tumor growth in xenograft models. Elevated serum levels of CCT3 have been observed in patients with lung cancer, exhibiting high diagnostic efficacy for distinguishing NSCLC from benign nodules (AUC=0.873) and enhancing performance for small cell lung cancer when combined with proGRP.ConclusionCCT3 facilitates the progression of lung cancer through the PI3 K/AKT-EMT axis, positioning it as a potential therapeutic target and biomarker.

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