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.

中文翻译：

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了解高钾血症与肺鳞癌之间的分子关联

先前的研究表明，高钾血症和肺鳞状细胞癌（LSCC）之间存在很强的联系。但是，到目前为止，尚未完全理解其基本机制。进行了基于文献的数据挖掘，以识别与高钾血症和LSCC相关的基因，分子和细胞过程。进行路径分析以探索两种疾病的互动网络，共同目标网络和共同调节网络。然后，使用11个独立的LSCC RNA表达数据集（358个LSCC和278个健康对照）进行了大规模分析，以检验影响高钾血症的基因也可能在LSCC中起作用的假设。与这两种疾病有关的基因之间存在显着重叠（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个分子是高钾血症和LSCC的常见靶标，还有19个分子是常见的调节剂。此外，在一个互动网络中鉴定出19个分子，高钾血症和LSCC可以通过该分子相互影响。此外，荟萃分析确定了一种高钾血症启动子SPP1作为LSCC的新贡献者（LFC = 2.64； p值= 2.81e-6）。MLR分析表明，地理区域是影响LSCC患者中SPP1表达水平的因素（p值= 0.036，0.054）。我们的研究结果表明，高钾血症和LSCC的病理学具有共同的分子基础，并且促进高钾血症的基因也可能在LSCC的发展中起作用。但是，这项研究并未提示高钙血症是LSCC的偶然因素。