<scp>KCND2</scp>: A prognostic biomarker and regulator of immune function in gastric cancer

Zhou, Hongying; Su, Dan; Chen, Yun; Zhang, Yiwen; Huang, Ping

doi:10.1002/cam4.6236

Cited by 6 publications

(4 citation statements)

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“…Ion channels had a key role in regulating the acid-base balance and metabolism of the TME, thereby affecting the activity and function of immune cells [44,45]. Among them, potassium channels could inhibit the anti-tumor ability of T cells and tumor-associated macrophages by increasing potassium ion concentration [46][47][48]. However, there were no reports on KCNK1 in BC TME as an important coding gene for potassium channels.…”

Section: Discussionmentioning

confidence: 99%

Overexpressed KCNK1 regulates potassium channels affecting molecular mechanisms and biological pathways in bladder cancer

Zhang,

Chen,

Wei

et al. 2024

Eur J Med Res

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Background This study aimed to explore the expression, molecular mechanism and its biological function of potassium two pore domain channel subfamily K member 1 (KCNK1) in bladder cancer (BC). Methods We integrated large numbers of external samples (n = 1486) to assess KCNK1 mRNA expression levels and collected in-house samples (n = 245) for immunohistochemistry (IHC) experiments to validate at the KCNK1 protein level. Single-cell RNA sequencing (scRNA-seq) analysis was performed to further assess KCNK1 expression and cellular communication. The transcriptional regulatory mechanisms of KCNK1 expression were explored by ChIP-seq, ATAC-seq and ChIA-PET data. Highly expressed co-expressed genes (HECEGs) of KCNK1 were used to explore potential signalling pathways. Furthermore, the immunoassay, clinical significance and molecular docking of KCNK1 were calculated. Results KCNK1 mRNA was significantly overexpressed in BC (SMD = 0.58, 95% CI [0.05; 1.11]), validated at the protein level (p < 0.0001). Upregulated KCNK1 mRNA exhibited highly distinguishing ability between BC and control samples (AUC = 0.82 [0.78–0.85]). Further, scRNA-seq analysis revealed that KCNK1 expression was predominantly clustered in BC epithelial cells and tended to increase with cellular differentiation. BC epithelial cells were involved in cellular communication mainly through the MK signalling pathway. Secondly, the KCNK1 transcription start site (TSS) showed promoter-enhancer interactions in three-dimensional space, while being transcriptionally regulated by GRHL2 and FOXA1. Most of the KCNK1 HECEGs were enriched in cell cycle–related signalling pathways. KCNK1 was mainly involved in cellular metabolism–related pathways and regulated cell membrane potassium channel activity. KCNK1 expression was associated with the level of infiltration of various immune cells. Immunotherapy and chemotherapy (docetaxel, paclitaxel and vinblastine) were more effective in BC patients in the high KCNK1 expression group. KCNK1 expression correlated with age, pathology grade and pathologic_M in BC patients. Conclusions KCNK1 was significantly overexpressed in BC. A complex and sophisticated three-dimensional spatial transcriptional regulatory network existed in the KCNK1 TSS and promoted the upregulated of KCNK1 expression. The high expression of KCNK1 might be involved in the cell cycle, cellular metabolism, and tumour microenvironment through the regulation of potassium channels, and ultimately contributed to the deterioration of BC.

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Section: Discussionmentioning

confidence: 99%

Overexpressed KCNK1 regulates potassium channels affecting molecular mechanisms and biological pathways in bladder cancer

Zhang,

Chen,

Wei

et al. 2024

Eur J Med Res

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“…VEGF can influence the autocrine survival of TNBC cells via NRP1 [39][40][41]. KCND2, which is a part of the potassium voltage-gated channel subfamily, has been recently reported to promote gastric cancer [42] and lung adenocarcinoma [43]. KCND2 has been earmarked by scientists as a crucial determinant in the prognosis of individuals with breast cancer.…”

Section: Discussionmentioning

confidence: 99%

Constructing a novel prognostic model for triple-negative breast cancer based on genes associated with vasculogenic mimicry

Ren,

Feng,

Tan

et al. 2024

Aging

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Background: Research has shown a connection between vasculogenic mimicry (VM) and cancer progression. However, the functions of genes related to VM in the emergence and progression of TNBC have not been completely elucidated. Methods: A survival risk model was constructed by screening biomarkers using DESeq2 and WGCNA based on public TNBC transcriptome data. Furthermore, gene set enrichment analysis was performed, and tumor microenvironment and drug sensitivity were analyzed. The selected biomarkers were validated via quantitative PCR detection, immunohistochemical staining, and protein detection in breast cancer cell lines. Biomarkers related to the proliferation and migration of TNBC cells were validated via in vitro experiments. Results: The findings revealed that 235 target genes were connected to the complement and coagulation cascade pathways. The risk score was constructed using KCND2, NRP1, and VSTM4. The prognosis model using the risk score and pathological T stage yielded good validation results. The clinical risk of TNBC was associated with the angiogenesis signaling pathway, and the low-risk group exhibited better sensitivity to immunotherapy. Quantitative PCR and immunohistochemistry indicated that the expression levels of KCND2 in TNBC tissues were higher than those in adjacent nontumor tissues. In the TNBC cell line, the protein expression of KCND2 was increased. Knockdown of KCND2 and VSTM4 inhibited the proliferation and migration of TNBC cells in vitro . Conclusions: In this study, three VM-related biomarkers were identified, including KCND2, NRP1, and VSTM4. These findings are likely to aid in deepening our understanding of the regulatory mechanism of VM in TNBC.

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“…Highlighted genes identified as significantly impacting outcome in Bueno (green) and TCGA (orange) human mesothelioma datasets. [ 74 ], [ 75 ], [ 76 ], [ 77 ], [ 78 ].…”

Section: Supplementary Materialsmentioning

confidence: 99%

The MexTAg collaborative cross: host genetics affects asbestos related disease latency, but has little influence once tumours develop

Fisher,

Patrick,

Hoang

et al. 2024

Front. Toxicol.

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Objectives: This study combines two innovative mouse models in a major gene discovery project to assess the influence of host genetics on asbestos related disease (ARD). Conventional genetics studies provided evidence that some susceptibility to mesothelioma is genetic. However, the identification of host modifier genes, the roles they may play, and whether they contribute to disease susceptibility remain unknown. Here we report a study designed to rapidly identify genes associated with mesothelioma susceptibility by combining the Collaborative Cross (CC) resource with the well-characterised MexTAg mesothelioma mouse model.Methods: The CC is a powerful mouse resource that harnesses over 90% of common genetic variation in the mouse species, allowing rapid identification of genes mediating complex traits. MexTAg mice rapidly, uniformly, and predictably develop mesothelioma, but only after asbestos exposure. To assess the influence of host genetics on ARD, we crossed 72 genetically distinct CC mouse strains with MexTAg mice and exposed the resulting CC-MexTAg (CCMT) progeny to asbestos and monitored them for traits including overall survival, the time to ARD onset (latency), the time between ARD onset and euthanasia (disease progression) and ascites volume. We identified phenotype-specific modifier genes associated with these traits and we validated the role of human orthologues in asbestos-induced carcinogenesis using human mesothelioma datasets.Results: We generated 72 genetically distinct CCMT strains and exposed their progeny (2,562 in total) to asbestos. Reflecting the genetic diversity of the CC, there was considerable variation in overall survival and disease latency. Surprisingly, however, there was no variation in disease progression, demonstrating that host genetic factors do have a significant influence during disease latency but have a limited role once disease is established. Quantitative trait loci (QTL) affecting ARD survival/latency were identified on chromosomes 6, 12 and X. Of the 97-protein coding candidate modifier genes that spanned these QTL, eight genes (CPED1, ORS1, NDUFA1, HS1BP3, IL13RA1, LSM8, TES and TSPAN12) were found to significantly affect outcome in both CCMT and human mesothelioma datasets.Conclusion: Host genetic factors affect susceptibility to development of asbestos associated disease. However, following mesothelioma establishment, genetic variation in molecular or immunological mechanisms did not affect disease progression. Identification of multiple candidate modifier genes and their human homologues with known associations in other advanced stage or metastatic cancers highlights the complexity of ARD and may provide a pathway to identify novel therapeutic targets.

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KCND2: A prognostic biomarker and regulator of immune function in gastric cancer

Cited by 6 publications

References 46 publications

Overexpressed KCNK1 regulates potassium channels affecting molecular mechanisms and biological pathways in bladder cancer

Overexpressed KCNK1 regulates potassium channels affecting molecular mechanisms and biological pathways in bladder cancer

Constructing a novel prognostic model for triple-negative breast cancer based on genes associated with vasculogenic mimicry

The MexTAg collaborative cross: host genetics affects asbestos related disease latency, but has little influence once tumours develop

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