Anti-Tumor Role of CAMK2B in Remodeling the Stromal Microenvironment and Inhibiting Proliferation in Papillary Renal Cell Carcinoma.
Anti-Tumor Role of CAMK2B in Remodeling the Stromal Microenvironment and Inhibiting Proliferation in Papillary Renal Cell Carcinoma.
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DOI：
10.3389/fonc.2022.740051
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发表时间：
2022
影响因子：
4.7
通讯作者：
Fu X
中科院分区：
文献类型：
--
作者：
Jia Q;Liao X;Zhang Y;Xu B;Song Y;Bian G;Fu X
肿瘤微环境（tumor microenvironment， TME）在不同肿瘤类型中是可变的，并且根据浸润间质细胞的类型和数量对恶性进展有不同的影响。特别是，TME效应基因及其竞争性内源性RNA （ceRNA）网络在调节恶性肿瘤进展中起着关键作用。然而，参与TME调节肾乳头状细胞癌（KIRP）的核心效应分子尚不清楚。为了解决这个问题，我们从癌症基因组图谱（TCGA）数据库中提取了233例KIRP患者，并使用ESTIMATE算法对数据进行处理。我们进一步评估了免疫评分（ISs）和基质评分（SSs）与疾病进展之间的关系，发现高SSs与KIRP的不良预后相关。因此，根据SS评分筛选差异表达基因（DEGs），得到2509个差异表达基因，包括1668个mrna， 783个长链非编码（lnc） rna和58个微（mi） rna。然后使用随机方差对deg进行过滤，并使用EPCLUST进行分层聚类。使用加权基因共表达网络分析（WGCNA）来评估这些deg的预后能力并识别目标ceRNA网络，并选择绿石模块中的lncRNA GUSBP11/miR-432-5p/CAMK2B作为有前景的ceRNA网络。从这个分析中，我们选择CAMK2B作为预测参与基质TMA调控的核心基因。因此，我们在体外和体内探索了CAMK2B的表达和功能，并提供了该蛋白促进KIRP中基质TME的调节和抑制增殖的证据。最后，我们发现血管内皮生长因子（VEGF）、转化生长因子(TGF)β和L1的同源物（CHL1）在KIRP中作为CAMK2B的下游效应因子。因此，在本研究中，我们发现TME通过核心效应分子CAMK2B决定KIRP患者的预后，CAMK2B介导微环境重塑和肿瘤进展。基于这些发现，我们提出基质微环境重塑可能是相对于免疫治疗KIRP的一种改进的治疗方法。
The tumor microenvironment (TME) is variable across tumor types and has diverse effects on malignant progression, based on the type and number of infiltrating stromal cells. In particular, TME effector genes and their competitive endogenous RNA (ceRNA) networks play a critical role in regulating malignant tumor progression. However, the core effector molecules involved in TME modulation of kidney renal papillary cell carcinoma (KIRP) are poorly understood. To address this question, a cohort containing 233 KIRP patients was derived from The Cancer Genome Atlas (TCGA) database, and the data were processed using the ESTIMATE algorithm. We further evaluated the relationship between immune scores (ISs) and stromal scores (SSs) and disease progression and found that high SSs were associated with a poor prognosis in KIRP. Differentially expressed genes (DEGs) were therefore screened based on SS scores, resulting in 2509 DEGs, including 1668 mRNAs, 783 long noncoding (lnc)RNAs, and 58 micro (mi)RNAs. DEGs were then filtered using the random variance and subjected to hierarchical clustering using EPCLUST. Weighted gene co-expression network analysis (WGCNA) was used to assess the prognostic capacity of these DEGs and identify target ceRNA networks, and lncRNA GUSBP11/miR-432-5p/CAMK2B in the turquoise module was selected as a promising ceRNA network. From this analysis CAMK2B was selected as the core gene predicted to be involved in stromal TMA regulation. We therefore explored the expression and function of CAMK2B in vitro and in vivo and provide evidence that this protein promotes stromal TME remodulation and inhibits proliferation in KIRP. Lastly, we show that vascular endothelial growth factor (VEGF), transforming growth factor (TGF)β, and close homolog of L1 (CHL1) act as downstream effectors of CAMK2B in KIRP. Thus, in this study, we show that the TME determines prognosis of KIRP patients via the core effector molecule CAMK2B, which mediates both microenvironmental remodeling and tumor progression. Based on these findings, we propose that remodeling of the stromal microenvironment could represent an improved therapeutic approach relative to immunotherapy for KIRP.
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DOI：
10.1155/2012/908601
发表时间：
2012
期刊：
Evidence-based complementary and alternative medicine : eCAM
影响因子：
--
作者：
Jia QA;Ren ZG;Bu Y;Wang ZM;Zhang QB;Liang L;Jiang XM;Zhang QB;Tang ZY
通讯作者：
Tang ZY
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：
8
作者：
Peng WX;Koirala P;Mo YY
通讯作者：
Mo YY
DOI：
10.1056/nejmoa1510665
发表时间：
2015-11-05
期刊：
The New England journal of medicine
影响因子：
--
作者：
Motzer RJ;Escudier B;McDermott DF;George S;Hammers HJ;Srinivas S;Tykodi SS;Sosman JA;Procopio G;Plimack ER;Castellano D;Choueiri TK;Gurney H;Donskov F;Bono P;Wagstaff J;Gauler TC;Ueda T;Tomita Y;Schutz FA;Kollmannsberger C;Larkin J;Ravaud A;Simon JS;Xu LA;Waxman IM;Sharma P;CheckMate 025 Investigators
通讯作者：
CheckMate 025 Investigators
影响因子：
64.8
作者：
Li S;Liu M;Do MH;Chou C;Stamatiades EG;Nixon BG;Shi W;Zhang X;Li P;Gao S;Capistrano KJ;Xu H;Cheung NV;Li MO
通讯作者：
Li MO