着丝粒蛋白F mRNA在肺腺癌细胞系、肺腺癌组织中的表达变化及相关调控信号通路分析

Objective To observe the expression changes of centromere protein F( CENPF) mRNA in the lung adenocarcinoma cell lines, and to analyze the expression changes of CENPF mRNA in the lung adenocarcinoma tissues and to explore its related regulatory signaling pathways. Methods ① The real-time quantitative PCR was used to detect the CENPF mRNA in the normal lung epithelial cell line BEAS-2 B and lung adenocarcinoma cell lines( A549, NCI-H1650, NCIH23, and NCI-H1975). ② The relationships of CENPF mRNA with clinicopathological characteristics and prognosis of lung adenocarcinoma were analyzed by the lung adenocarcinoma dataset of Cancer Genome Atlas( TCGA). Cox regression model was used to analyze the prognostic factors of lung adenocarcinoma patients. Gene Set Enrichment Analysis( GSEA) was used to analyze the signal pathways involved in lung adenocarcinoma regulated by CENPF. Results The relative expression of CENPF mRNA in the A549, NCI-H1650, NCI-H23, NCI-H1975, and BEAS-2 B cells were 4. 333 ±0. 271, 3. 193 ± 0. 188, 2. 770 ± 0. 091, 5. 491 ± 0. 249, and 1. 006 ± 0. 071, respectively. The relative expression of CENPF mRNA in the A549, H1650, NCI-H23, and NCI-H1975 cells was higher than that in the BEAS-2 B cells( P <0. 05). The relative expression levels of CENPF mRNA in the lung adenocarcinoma and adjacent normal tissues were9. 632 ± 0. 059 and 6. 472 ± 0. 093, with significant difference( P < 0. 001). CENPF mRNA expression was related to gender, age, T stage, N stage, and TNM stage( all P < 0. 05). Survival analysis showed that patients with high CENPF mRNA expression had poorer prognosis compared with patients with low CENPF mRNA expression( P = 0. 001). Cox regression model analysis showed that CENPF mRNA expression and TNM staging were independent risk factors for the prognosis of lung adenocarcinoma patients( HR = 1. 667 and 1. 414, respectively, both P < 0. 01). The lung adenocarcinoma regulatory signaling pathway associated with high expression of CENPF mRNA included G2 M checkpoint( P < 0. 001, FDR <0. 001), mitotic spindle( P < 0. 001, FDR < 0. 001), E2 F target gene( P < 0. 001, FDR < 0. 001), MYC target gene( P< 0. 001, FDR = 0. 001), m TOR signaling pathway( P = 0. 002, FDR = 0. 005), spermatogenesis( P = 0. 002, FDR =0. 009), unfolded protein response( P = 0. 002, FDR = 0. 020), and PI3 K/Akt/m TOR signaling pathway( P = 0. 015, FDR = 0. 117). Conclusions CENPF mRNA is highly expressed in the lung adenocarcinoma tissues and cell lines. The high expression of CENPF mRNA is closely related to the clinicopathological characteristics and poor prognosis of lung adenocarcinoma patients. High expression of CENPF mRNA is an independent risk factor for the prognosis of lung adenocarcinoma patients. CENPF mRNA may play an important role in the development and progression of lung adenocarcinoma by regulating G2 M checkpoint, mitotic spindle, E2 F target gene, MYC target gene, m TOR signaling pathway, spermatogenesis, unfolded protein response, and PI3 K/Akt/m TOR signaling pathway. [ABSTRACT FROM AUTHOR]