Department of Radiology, Jiangyin People's Hospital, Jiangyin, 214400, Jiangsu Province, China.
Department of Cardiothoracic Surgery, The affiliated Jiangyin Hospital of Southeast University Medical College, Jiangyin, 214400, Jiangsu, China.
BMC Med Genet. 2020 Oct 22;21(Suppl 1):176. doi: 10.1186/s12881-020-01099-7.
Previous studies indicated a strong association between hyperkalemia and lung squamous cell carcinomas (LSCC). However, the underlying mechanism is not fully understood so far.
Literature-based data mining was conducted to identify genes, molecule, and cell processes linked to both hyperkalemia and LSCC. Pathway analysis was performed to explore the interactive network, common-target network, and common-regulator network for both disorders. Then, a mega-analysis using 11 independent LSCC RNA expression datasets (358 LSCCs and 278 healthy controls) was performed to test the hypothesis that genes influencing hyperkalemia may also play roles in LSCC.
There was a significant overlap between the genes implicated with both diseases (20 genes, p-value = 4.98e-15), which counts for 16% of all hyperkalemia genes (125 genes). Network analysis identified 12 molecules as common targets for hyperkalemia and LSCC, and 19 molecules as common regulators. Moreover, 19 molecules were identified within an interactive network, through which hyperkalemia and LSCC could exert influence on each other. In addition, meta-analysis identified one hyperkalemia promoter, SPP1, as a novel contributor for LSCC (LFC = 2.64; p-value = 2.81e-6). MLR analysis suggests geographical region as an influential factor for the expression levels of SPP1 in LSCC patients (p value = 0.036, 0.054).
Our results showed that there was a common molecular basis for the pathology of both hyperkalemia and LSCC, and that genes promoting hyperkalemia might also play roles in the development of LSCC. However, this study did not suggest hypercalcemia as a casual factor for LSCC.
先前的研究表明高钾血症与肺鳞状细胞癌（LSCC）之间存在很强的关联性。然而，到目前为止，其潜在机制尚未完全阐明。
进行基于文献的数据分析，以确定与高钾血症和 LSCC 均相关的基因、分子和细胞过程。进行途径分析，以探索两种疾病的交互网络、共同靶标网络和共同调控网络。然后，对 11 个独立的 LSCC RNA 表达数据集（358 例 LSCC 和 278 例健康对照）进行 mega 分析，以检验“影响高钾血症的基因也可能在 LSCC 中发挥作用”这一假说。
两种疾病相关的基因存在显著重叠（20 个基因，p 值=4.98e-15），占所有高钾血症基因（125 个基因）的 16%。网络分析确定了 12 个分子作为高钾血症和 LSCC 的共同靶标，以及 19 个分子作为共同调节剂。此外，通过相互作用网络鉴定了 19 个分子，通过该网络，高钾血症和 LSCC 可以相互影响。此外，荟萃分析确定了一个高钾血症启动子 SPP1 作为 LSCC 的一个新贡献者（LFC=2.64;p 值=2.81e-6）。MLR 分析表明，地理区域是 LSCC 患者 SPP1 表达水平的一个影响因素（p 值=0.036，0.054）。
我们的研究结果表明，高钾血症和 LSCC 的病理存在共同的分子基础，促进高钾血症的基因也可能在 LSCC 的发生中发挥作用。然而，本研究并未提示高钙血症是 LSCC 的一个偶然因素。
