A Meta-Analysis Study to Infer Voltage-Gated K+ Channels Prognostic Value in Different Cancer Types

Abstract

Potassium channels are often highly expressed in cancer cells with respect to healthy ones, as they provide proliferative advantages through modulating membrane potential, calcium homeostasis, and various signaling pathways. Among potassium channels, Shaker type voltage-gated Kv channels are emerging as promising pharmacological targets in oncology. Here, we queried publicly available cancer patient databases to highlight if a correlation exists between Kv channel expression and survival rate in five different cancer types. By multiple gene comparison analysis, we found a predominant expression of KCNA2, KCNA3, and KCNA5 with respect to the other KCNA genes in skin cutaneous melanoma (SKCM), uterine corpus endometrial carcinoma (UCEC), stomach adenocarcinoma (STAD), lung adenocarcinoma (LUAD), and lung squamous cell carcinoma (LUSC). This analysis highlighted a prognostic role of KCNA3 and KCNA5 in SKCM, LUAD, LUSC, and STAD, respectively. Interestingly, KCNA3 was associated with a positive prognosis in SKCM and LUAD but not in LUSC. Results obtained by the analysis of KCNA3-related differentially expressed genes (DEGs); tumor immune cell infiltration highlighted differences that may account for such differential prognosis. A meta-analysis study was conducted to investigate the role of KCNA channels in cancer using cancer patients’ datasets. Our study underlines a promising correlation between Kv channel expression in tumor cells, in infiltrating immune cells, and survival rate.

Antiproliferative, Antioxidant, Chemopreventive and Antiangiogenic Potential of Chromatographic Fractions from Anemonia sulcata with and without Its Symbiont Symbiodinium in Colorectal Cancer Therapy

“…Dysregulation of potassium channels has also been implicated in tumor initiation and growth [61]. Toxins from sea anemones, including kaliseptine and kalicludine-1, -2, or -3, have been shown to inhibit Kv1.2 channels, which are overexpressed in various cancers [62]. BDS toxins block Kv3 channels, such as Kv3.1 and Kv3.4 subtypes, which play a role in cancer cell migration and invasion and have been detected in colonic crypt cells of mice with induced CRC and in the T84 cell line [63][64][65][66].…”

Ion channels in lung cancer: biological and clinical relevance

“…Among VGKC, different members (Kv1.3, Kv3.1, Kv3.4, Kv4.2, Kv5.1, Kv7.1, Kv9.3, Kv10.1, and Kv11.1) are involved in LC cell proliferation, migration and invasion ( Jang et al, 2011a ; Restrepo-Angulo et al, 2011 ; Glassmeier et al, 2012 ; Girault et al, 2014 ; Acuña-Macías et al, 2015 ; Lee et al, 2015 ; Chen et al, 2023 ) and some of them (Kv1.3, Kv4.2, and Kv7.1) have clinical relevance in NSCLC ( Girault et al, 2014 ; Lu X. et al, 2021 ; Chang et al, 2022 ; Angi et al, 2023 ) ( Table 4 ).…”