CALD1 promotes the expression of PD-L1 in bladder cancer via the JAK/STAT signaling pathway.
CALD1 promotes the expression of PD-L1 in bladder cancer via the JAK/STAT signaling pathway.
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CALD 1通过JAK/STAT信号通路促进膀胱癌中PD-L1的表达。
DOI：
10.21037/atm-21-4192
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发表时间：
2021-09
影响因子：
--
通讯作者：
Yao X
中科院分区：
文献类型：
--
作者：
Li C;Yang F;Wang R;Li W;Maskey N;Zhang W;Guo Y;Liu S;Wang H;Yao X
膀胱癌（BC）是一种常见的恶性肿瘤，尽管有最佳的治疗，但复发率和进展率很高。迫切需要鉴定用于BC靶向治疗的新的有效生物标志物。通过加权基因共表达网络分析（WGCNA）从BC的编码蛋白基因中筛选出关键基因CALD 1。在癌症基因组图谱（TCGA）和基因表达综合数据库（GEO）中探索了临床和预后意义。采用CCK-8细胞计数试剂盒、流式细胞仪、transwell小室实验和裸鼠移植瘤实验检测细胞生长、凋亡、迁移、侵袭和成瘤能力。在肿瘤免疫评估资源（TIMER）数据库中分析免疫相关性。使用基因集富集分析（GSEA）探索相关信号通路。CALD 1的高表达与组织学分级、临床分期、T分期及淋巴结转移密切相关。Kaplan-Meier生存曲线显示，在TCGA数据库中CALD 1高表达与总生存期（OS）和无病生存期（DFS）差相关，在4个GEO数据库中与OS差相关。 CALD 1在体内外均能促进肿瘤细胞的生长、迁移、侵袭和细胞周期的调节，抑制肿瘤细胞的凋亡。CADL 1表达与CD 274水平升高呈正相关（r=0.357，P=9.71e−14）。JAK/STAT信号通路在CALD 1高表达组中明显富集。CALD 1介导的PD-L1过表达（OE）是通过激活JAK/STAT信号通路实现的;这种作用被特异性JAK抑制剂Ruxolitinib阻断。CALD 1是一个潜在的与预后相关的分子标志物。它通过JAK/STAT信号通路促进BC的恶性进展并上调PD-L1表达。
Bladder cancer (BC) is a common malignant neoplasm with a high rate of recurrence and progression, despite optimal treatment. There is a pressing need to identify new effective biomarkers for the targeted treatment of BC. The key gene CALD1 was screened via weighed gene co-expression network analysis (WGCNA) from encoding protein genes of BC. Clinical and prognostic significance was explored in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Cell Counting Kit-8 (CCK-8), flow cytometry, transwell chamber experiment and nude mouse xenograft assay were performed to test cell growth, apoptosis, migration, invasion and tumorigenesis capacities. Immune correlation was analyzed in The Tumor Immune Estimation Resource (TIMER) database. Relevant signaling pathways were explored using gene set enrichment analysis (GSEA). Increased expression of CALD1 was significantly correlated with histological grade, clinical stage, T stage, and lymphatic metastasis. Kaplan-Meier survival curves showed that high CALD1 expression was associated with poor overall survival (OS) and disease-free survival (DFS) in TCGA database, and with poor OS in the four GEO databases. CALD1 promotes growth, migration, invasion, and cell cycle of tumor cell, and inhibits tumor cell apoptosis in vitro and in vivo. CADL1 expression was positively correlated with increased CD274 levels (r=0.357, P=9.71e−14). JAK/STAT signaling pathway was significantly enriched in the high CALD1 expression group. CALD1-mediated PD-L1 overexpression (OE) was via the activation of the JAK/STAT signaling pathway; this effect was blocked by the specific JAK inhibitor Ruxolitinib. CALD1 is a potential molecular marker associated with prognosis. It promotes the malignant progression of BC and upregulates the PD-L1 expression via the JAK/STAT signaling pathway.
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影响因子：
5.2
作者：
Lopez-Beltran A;Cimadamore A;Blanca A;Massari F;Vau N;Scarpelli M;Cheng L;Montironi R
通讯作者：
Montironi R
影响因子：
2.1
作者：
Faraj SF;Munari E;Guner G;Taube J;Anders R;Hicks J;Meeker A;Schoenberg M;Bivalacqua T;Drake C;Netto GJ
通讯作者：
Netto GJ
DOI：
10.1038/nrc3239
发表时间：
2012-03-22
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
Pardoll DM
通讯作者：
Pardoll DM
影响因子：
5.8
作者：
Polpitiya, Ashoka D.;Qian, Wei-Jun;Smith, Richard D.
通讯作者：
Smith, Richard D.
影响因子：
4.7
作者：
Lim, Byungho;Park, Jong-Lyul;Kim, Seon-Young
通讯作者：
Kim, Seon-Young