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Abstract：
The role of cathepsin K (CTSK) expression in the pathogenesis and progression of gastric cancer (GC) remains unclear. Hence, the primary objective of this study is to elucidate the precise expression and biological role of CTSK in GC by employing a combination of bioinformatics analysis and in vitro experiments. Our findings indicated a significant upregulation of CTSK in GC. The bioinformatics analysis revealed that GC patients with a high level of CTSK expression exhibited enrichment of hallmark gene sets associated with angiogenesis, epithelial-mesenchymal transition (EMT), inflammatory response, KRAS signaling up, TNFα signaling via KFκB, IL2-STAT5 signaling, and IL6-JAK-STAT3 signaling. Additionally, these patients demonstrated elevated levels of M2-macrophage infiltration, which was also correlated with a poorer prognosis. The results of in vitro experiments provided confirmation that the over-expression of CTSK leads to an increase in the proliferative and invasive abilities of GC cells. However, further evaluation was necessary to determine the impact of CTSK on the migration capability of these cells. Our findings suggested that CTSK has the potential to facilitate the initiation and progression of GC by augmenting the invasive capacity of GC cells, engaging in tumor-associated EMT, and fostering the establishment of an immunosuppressive tumor microenvironment (TME).
摘要：
组织蛋白酶K（CTSK）的表达在胃癌（GC）的发生发展中的作用尚不清楚。因此，这项研究的主要目的是通过生物信息学分析和体外实验相结合，阐明CTSK在GC中的精确表达和生物学作用。我们的发现表明GC中CTSK的显着上调。生物信息学分析显示，CTSK表达水平高的GC患者表现出与血管生成相关的标志基因集的富集，上皮-间质转化（EMT），炎症反应，KRAS发出信号，TNFα信号通过KFκB，IL2-STAT5信令,和IL6-JAK-STAT3信号。此外,这些患者表现出M2-巨噬细胞浸润水平升高，这也与预后较差有关。体外实验的结果证实了CTSK的过表达导致GC细胞的增殖和侵袭能力增加。然而,需要进一步评估以确定CTSK对这些细胞迁移能力的影响。我们的研究结果表明，CTSK有可能通过增强GC细胞的侵袭能力来促进GC的启动和进展。参与肿瘤相关的EMT，促进建立免疫抑制肿瘤微环境(TME)。
