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Published on: January 22, 2018
KCND2: A prognostic biomarker and regulator of immune function in gastric cancer
Hongying Zhou1,2, Dan Su3, Yun Chen2
1SuZhou Medical College of Soochow University, Suzhou, Jiangsu Province, China.
Background:
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.
Methods:
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.
Results:
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.
Conclusion:
Overall, these findings suggest that KCND2 is likely to be available as an underlying therapeutic target for gastric cancer.
Insights
Potassium voltage-gated channel subfamily D member 2 (KCND2) is elevated in gastric cancer, promoting tumor growth and M2 macrophage infiltration via NF-κB signaling. This suggests KCND2 is a potential therapeutic target for gastric cancer.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- Gastric cancer is a heterogeneous disease, complicating targeted therapy development.
- Potassium voltage-gated channel subfamily D member 2 (KCND2) involvement in cancers is known, but its role in gastric cancer requires further elucidation.
Purpose of the Study:
- To investigate the role of KCND2 in gastric cancer progression.
- To analyze the correlation between KCND2 expression, clinical features, and immune infiltration in gastric cancer.
Main Methods:
- Utilized TCGA database for expression and clinical correlation analysis.
- Performed in vitro assays (CCK8, clone formation, cell cycle) and in vivo studies.
- Employed immunofluorescence, flow cytometry, and qRT-PCR to assess proliferation and immune cell infiltration.
Main Results:
- KCND2 expression is elevated in gastric cancer and correlates with advanced tumor grade and stage.
- Elevated KCND2 predicts a poorer prognosis and enhances gastric cancer cell proliferation and viability.
- KCND2 promotes gastric cancer progression by stimulating NF-κB signaling, leading to M2 macrophage infiltration.
Conclusions:
- KCND2 plays a significant role in promoting gastric cancer growth and immune evasion.
- KCND2 represents a promising therapeutic target for gastric cancer treatment.
