期刊：
Frontiers in Genetics,2020年11:591079 ISSN：1664-8021
通讯作者：
Luo, GQ
作者机构：
[Luo, Guoqing; Zhuang, Gaojian] Guangzhou Med Univ, Qingyuan Peoples Hosp, Affiliated Hosp 6, Qingyuan, Peoples R China.;[Zeng, Yu] Tianjin Med Univ Canc Inst & Hosp, Key Lab Canc Prevent & Therapy, Dept Thyroid & Neck Tumor, Natl Clin Res Ctr Canc, Tianjin, Peoples R China.;[Tang, Qun] Hunan Univ Chinese Med, Dept Pathol, Changsha, Peoples R China.;[He, Qian] Jinan Univ, Affiliated Hosp 1, Dept Neurosurg, Guangzhou, Peoples R China.
通讯机构：
[Luo, GQ ] G;Guangzhou Med Univ, Qingyuan Peoples Hosp, Affiliated Hosp 6, Qingyuan, Peoples R China.
关键词：
M1 macrophages;CIBERSORT;weighted gene co-expression network analysis (WGCNA);nomogram;thyroid cancer (THCA)
摘要：
Macrophages are key innate immune cells in the tumor microenvironment that regulate primary tumor growth, vascularization, metastatic spread and response to therapies. Macrophages can polarize into two different states (M1 and M2) with distinct phenotypes and functions. To investigate the known tumoricidal effects of M1 macrophages, we obtained RNA expression profiles and clinical data from The Cancer Genome Atlas Thyroid Cancer (TCGA-THCA). The proportions of immune cells in tumor samples were assessed using CIBERSORT, and weighted gene co-expression network analysis (WGCNA) was used to identify M1 macrophage-related modules. Univariate Cox analysis and LASSO-Cox regression analysis were performed, and four genes (SPP1, DHRS3, SLC11A1, and CFB) with significant differential expression were selected through GEPIA. These four genes can be considered hub genes. The four-gene risk-scoring model may be an independent prognostic factor for THCA patients. The validation cohort and the entire cohort confirmed the results. Univariate and multivariate Cox analysis was performed to identify independent prognostic factors for THCA. Finally, a prognostic nomogram was built based on the entire cohort, and the nomogram combining the risk score and clinical prognostic factors was superior to the nomogram with individual clinical prognostic factors in predicting overall survival. Time-dependent ROC curves and DCA confirmed that the combined nomogram is useful. Gene set enrichment analysis (GSEA) was used to elucidate the potential molecular functions of the high-risk group. Our study identified four genes associated with M1 macrophages and established a prognostic nomogram that predicts overall survival for patients with THCA, which may help determine clinical treatment options for different patients.
摘要：
<jats:title>Abstract</jats:title>
<jats:p>Aim: To investigate the relationship between PI3K/Akt/NF-κB cellular signal pathway and the expression of P-gp and LRP in multidrug resistance (MDR) cell of nasopharyngeal carcinoma.</jats:p>
<jats:p>Method: The PI3K, p-Akt and NF-κB/p65 as the activity of PI3K/Akt/NF-κB were detected by Western blot. The expressions of LRP and P-gp were detected by Western blot and real-time PCR.</jats:p>
<jats:p>Result: The RIs of CNE/DDP group to DDP, 5-Fu, VCR, ADR and PTX were 35.04, 18.14, 24.13, 12.00 and 10.18, respectively. The RIs of LY-294002 group were 11.77, 5.83, 3.07, 3.86 and 3.34, and PDTC group were 11.08, 6.55, 7.66, 2.18 and 4.05. The expressions of PI3K, p-Akt and NF-κBp65, LRP and P-gp were increased and mRNA of LRP and P-gp were up-regulated in CNE/DDP. The expression of p-Akt in LY-294002 group was down-regulated. The expression of NF-κB p65 in PDTC group was decreased. The mRNA of LRP and P-gp in LY-294002 group and PDTC group were decreased.</jats:p>
<jats:p>Conclusion: MDR of nasopharyngeal carcinoma cell can be regulated by activating PI3K/Akt/NF-κB signal pathway and then increase the expression of P-gp and LRP. The MDR of nasopharyngeal carcinoma cell can be reversed by inhibiting PI3K/Akt/NF-κB signal pathway.</jats:p>
作者机构：
[唐群; 朱伟; 刘春燕] Dept of Pathology, Hunan University of Chinese Medicine, Changsha, 410208, China;[杨胜辉] Dept of Preventive Medicine, Hunan University of Chinese Medicine, Changsha, 410208, China;[Zeng H.] Dept of Physiology, Hunan University of Chinese Medicine, Changsha, 410208, China
作者机构：
[朱伟; 唐群; 刘春燕] Dept of Pathology, Hunan University of Chinese Medicine, Changsha, 410208, China;[杨胜辉] Dept of Preventive Medicine, Hunan University of Chinese Medicine, Changsha, 410208, China;[Zeng H.] Dept of Physiology, Hunan University of Chinese Medicine, Changsha, 410208, China;[魏科] Dept of Microbiology, Hunan University of Chinese Medicine, Changsha, 410208, China
