SPOCK1, as a potential prognostic and therapeutic biomarker for lung adenocarcinoma, is associated with epithelial-mesenchymal transition and immune evasion.
SPOCK1, as a potential prognostic and therapeutic biomarker for lung adenocarcinoma, is associated with epithelial-mesenchymal transition and immune evasion.
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SPOCK 1作为肺腺癌潜在的预后和治疗生物标志物，与上皮-间质转化和免疫逃避相关。
DOI：
10.1186/s12967-023-04616-3
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发表时间：
2023-12-12
影响因子：
7.4
通讯作者：
Hu, Dong
中科院分区：
文献类型：
--
作者：
Liu, Yafeng;Han, Tao;Wu, Jing;Zhou, Jiawei;Guo, Jianqiang;Miao, Rui;Xu, Zhi;Xing, Yingru;Bai, Ying;Hu, Dong
上皮间质转化（EMT）和免疫逃避被认为是肺腺癌（LUAD）预后不良的原因。因此，本研究旨在探索促进EMT和免疫逃避的关键癌基因，并揭示其表达模式，预后价值和潜在的生物学功能。首先，我们通过加权基因共表达网络分析（WGCNA）确定了与EMT和肿瘤免疫功能障碍和排斥（TIDE）相关的基因模块。接下来，我们利用差异分析和机器学习来识别关键基因并对其进行验证。并分析了关键基因与肿瘤微环境重塑、药物敏感性及突变频率的相关性。并通过体外实验和临床标本验证其恶性生物学特性。最后，基于CMap筛选出治疗LUAD的潜在药物，并通过实验进行验证。首先，WGCNA分析表明，红色和绿色模块与EMT和TIDE高度相关。其中，SPOCK 1在肺腺癌组织中表达上调，且与预后不良相关。此外，高SPOCK 1组的患者表现出更多的恶性致癌途径激活，免疫抑制成分浸润更高，突变频率更高。SPOCK 1基因敲低可抑制肺腺癌细胞的侵袭和转移能力，SPOCK 1的高表达与CD 8 + T细胞的低浸润相关。在治疗方面，SPOCK 1可以是药物敏感性的候选指标，并且CMap显示VER-155008是对SPOCK 1表达谱具有最大扰动效应的候选药物。体外和体内实验验证了VER-155008在LUAD中的抑癌作用。本研究通过综合生物信息学分析和实验分析，揭示了SPOCK 1在LUAD中具有促进EMT和免疫逃逸的作用，有望成为LUAD的候选预后生物标志物和治疗靶点。在线版本包含补充材料，可通过10.1186/s12967-023-04616-3获得。
The occurrence of epithelial-mesenchymal transition (EMT) and immune evasion is considered to contribute to poor prognosis in lung adenocarcinoma (LUAD). Therefore, this study aims to explore the key oncogenes that promote EMT and immune evasion and reveal the expression patterns, prognostic value, and potential biological functions. Firstly, we identified gene modules associated with EMT and Tumor Immune Dysfunction and Exclusion (TIDE) through weighted gene co-expression network analysis (WGCNA). Next, we utilized differential analysis and machine learning to identify the key genes and validate them. Moreover, we analyzed the correlation between key genes and tumor microenvironment remodeling, drug sensitivity, as well as mutation frequency. Furthermore, we explored and validated their malignant biological characteristics through in vitro experiments and clinical samples. Finally, potential drugs for LUAD were screened based on CMap and validated through experiments. Firstly, WGCNA analysis revealed that red and green modules were highly correlated with EMT and TIDE. Among them, upregulated expression of SPOCK1 was observed in lung adenocarcinoma tissues and was associated with poor prognosis. Additionally, patients in the high SPOCK1 group showed more activation of malignant oncogenic pathways, higher infiltration of immunosuppressive components, and a higher frequency of mutations. The knockdown of SPOCK1 suppressed invasion and metastasis capabilities of lung adenocarcinoma cells, and the high expression of SPOCK1 was associated with low infiltration of CD8+ T cells. Therapeutic aspects, SPOCK1 can be a candidate indicator for drug sensitivity and CMap showed that VER-155008 was the drug candidate with the largest perturbation effect on the SPOCK1 expression profile. In vitro and in vivo experiments validated the cancer-inhibitory effect of VER-155008 in LUAD. This study revealed through comprehensive bioinformatics analysis and experimental analysis that SPOCK1 can promote EMT and immune escape in LUAD, and it may serve as a promising candidate prognostic biomarker and therapeutic target for LUAD. The online version contains supplementary material available at 10.1186/s12967-023-04616-3.
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DOI：
10.2147/dddt.s91321
发表时间：
2016
期刊：
Drug design, development and therapy
影响因子：
--
作者：
Chen Q;Yao YT;Xu H;Chen YB;Gu M;Cai ZK;Wang Z
通讯作者：
Wang Z
WGCNA：用于加权相关网络分析的 R 包。
影响因子：
3
作者：
Langfelder P;Horvath S
通讯作者：
Horvath S
影响因子：
50.3
作者：
Jain RK
通讯作者：
Jain RK
影响因子：
82.9
作者：
Binnewies M;Roberts EW;Kersten K;Chan V;Fearon DF;Merad M;Coussens LM;Gabrilovich DI;Ostrand-Rosenberg S;Hedrick CC;Vonderheide RH;Pittet MJ;Jain RK;Zou W;Howcroft TK;Woodhouse EC;Weinberg RA;Krummel MF
通讯作者：
Krummel MF
DOI：
10.1158/1078-0432.ccr-15-1434
发表时间：
2016-07-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Lou Y;Diao L;Cuentas ER;Denning WL;Chen L;Fan YH;Byers LA;Wang J;Papadimitrakopoulou VA;Behrens C;Rodriguez JC;Hwu P;Wistuba II;Heymach JV;Gibbons DL
通讯作者：
Gibbons DL