Department of Urology, Shengjing Hospital of China Medical University, Shenyang, China.
Department of Radiology, Shengjing Hospital of China Medical University, Shenyang, China.
Gene. 2021 Apr 5;775:145451. doi: 10.1016/j.gene.2021.145451. Epub 2021 Jan 20.
Bladder urothelial cancer (BLCA) has a high incidence worldwide. Cancer-associated fibroblasts (CAFs) in the tumor microenvironment are gradually recognized to play an important role in the occurrence and progression of cancer. However, the research on BLCA CAFs is still in its infancy, and the CAFs related genes are still unclear. We used the identified BLCA-specific CAFs gene signature in our previous work to calculate the CAFs infiltration score of the sample. Furthermore, we used data from multiple public databases to prove that CAFs high infiltration is associated with tumor progression and poor prognosis. In order to select the powerful genes in BLCA that are related to CAFs infiltration and affect prognosis, we chose transcription factors as the research object, and finally defined RUNX2 as the candidate gene for functional verification. In the immunohistochemical images, tissues with higher RUNX2 expression also had deeper staining of CAFs markers. We used public databases and collected specimens to prove that RUNX2 is overexpressed at the mRNA and protein levels in BLCA tissues. Through functional enrichment analysis, RUNX2 is mainly related to epithelialmesenchymal transition and extracellular matrix. Finally, we knocked down RUNX2 in vitro and observed a significant decrease in the metastasis and proliferation ability. In conclusion, high infiltration of CAFs is associated with tumor progression and poor prognosis in BLCA. RUNX2 is a transcription factor related to CAFs, which is overexpressed in bladder cancer and affects the prognosis. RUNX2 is a potential marker relating CAFs and therapy target in BLCA.
膀胱癌（BLCA）在全球范围内发病率较高。肿瘤微环境中的癌症相关成纤维细胞（CAFs）逐渐被认为在癌症的发生和发展中发挥重要作用。然而，BLCA 相关 CAFs 的研究仍处于起步阶段，CAFs 相关基因仍不清楚。我们在前一项工作中使用鉴定的 BLCA 特异性 CAFs 基因特征来计算样本的 CAFs 浸润评分。此外，我们使用来自多个公共数据库的数据证明 CAFs 高浸润与肿瘤进展和预后不良相关。为了筛选与 CAFs 浸润相关并影响预后的 BLCA 中的有力基因，我们选择转录因子作为研究对象，最终将 RUNX2 定义为功能验证的候选基因。在免疫组化图像中，RUNX2 表达较高的组织 CAFs 标志物染色也更深。我们使用公共数据库和收集的标本证明 RUNX2 在 BLCA 组织中在 mRNA 和蛋白水平上均过度表达。通过功能富集分析，RUNX2 主要与上皮间质转化和细胞外基质有关。最后，我们在体外敲低 RUNX2，观察到转移和增殖能力显著下降。总之，CAFs 的高浸润与 BLCA 中的肿瘤进展和预后不良相关。RUNX2 是一种与 CAFs 相关的转录因子，在膀胱癌中过度表达，影响预后。RUNX2 是 BLCA 中与 CAFs 相关的潜在标志物和治疗靶点。
