SuZhou Medical College of Soochow University, Suzhou, Jiangsu Province, China.
Department of Medical Oncology, Cancer Center, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, China.
Cancer Med. 2023 Aug;12(15):16279-16294. doi: 10.1002/cam4.6236. Epub 2023 Jun 22.
Gastric cancer is a highly heterogeneous disease, which makes it challenging to develop effective targeted therapies. Although the potassium voltage-gated channel subfamily D (KCND) channels, particularly KCND2 (also known as Kv4.2), have found evidence of involvement in the occurrence and development of various cancers, there are still some limitations in our understanding of KCND2's roles in gastric cancer.
We analyzed the correlation between KCND2 expression and clinical features as well as immune infiltration using the Cancer Genome Atlas (TCGA) database. Functional assays of KCND2 were conducted using Cell counting Kit-8 (CCK8), clone formation assay and cell cycle analysis. Additionally, immunofluorescence, flow cytometry and quantitative real-time polymerase chain reaction (qRT-PCR) techniques were used to investigate tumor proliferation and immune cell infiltration at different levels of KCND2 expression in vivo.
KCND2 was markedly elevated in gastric cancer and its expression appeared to link to different grades, T stages, and N stages. In addition, KCND2 was an independent predictor of prognosis, and its elevated levels in TCGA database revealed a more unfavorable prognosis for patients with gastric cancer. KCND2 strengthened the viability at the cellular level by boosting the proliferation of gastric cancer cells and reducing their death rate. Additionally, it also highlights that KCND2 the abilities of proliferating of gastric cancer cells by stimulating NF-κB both in cell and animal levels. In addition, the findings provided proof that in animal levels, KCND2 might regulate the immune system by associating with promoting M2 macrophages, which are known to play critical roles in cancer progression. Mechanistically, KCND2 was found to lead to the infiltration of M2 macrophages through activation of NF-κB, ultimately promoting the advancement of gastric cancer.
Overall, these findings suggest that KCND2 is likely to be available as an underlying therapeutic target for gastric cancer.
胃癌是一种高度异质性的疾病，这使得开发有效的靶向治疗方法具有挑战性。尽管钾电压门控通道亚家族 D（KCND）通道，特别是 KCND2（也称为 Kv4.2），已被证明参与了各种癌症的发生和发展，但我们对 KCND2 在胃癌中的作用仍存在一些认识上的局限性。
我们使用癌症基因组图谱（TCGA）数据库分析了 KCND2 表达与临床特征和免疫浸润之间的相关性。使用细胞计数试剂盒-8（CCK8）、克隆形成实验和细胞周期分析进行 KCND2 的功能测定。此外，还通过免疫荧光、流式细胞术和定量实时聚合酶链反应（qRT-PCR）技术，在体内不同 KCND2 表达水平下研究肿瘤增殖和免疫细胞浸润。
KCND2 在胃癌中明显升高，其表达似乎与不同的分级、T 分期和 N 分期有关。此外，KCND2 是预后的独立预测因子，其在 TCGA 数据库中的升高水平表明胃癌患者的预后更差。KCND2 通过增强胃癌细胞的增殖和降低死亡率来增强细胞水平的活力。此外，它还强调了 KCND2 通过在细胞和动物水平刺激 NF-κB，增强了胃癌细胞的增殖能力。此外，研究结果表明，在动物水平上，KCND2 可能通过与促进 M2 巨噬细胞相关来调节免疫系统，M2 巨噬细胞在癌症进展中起着关键作用。从机制上讲，KCND2 通过激活 NF-κB 导致 M2 巨噬细胞浸润，最终促进胃癌的进展。
总的来说，这些发现表明 KCND2 可能成为胃癌的潜在治疗靶点。
