Bioinformatic analysis of the role of S100A9 inhibition on reducing the brain metastasis in EGFR-mutant lung cancer

Abstract

Lung cancer is the most relevant cause of cancer deaths all over the world. Non-small cell lung cancer (NSCLC) is the most common type. Brain metastasis (BM) is a serious challenge for about 30-40% of these patients that not only has an important effect on cancer prognosis but also complicates the treatment approaches (Ma.et al. 2024). S100A9 is a calcium binding protein that was first identified in the of multiple inflammatory pathways. Later, Other investigators have mentioned it as migration inhibitory factor related protein (MRP) because of its ability to translocate to keratin intermediate filaments in response to calcium stimulation. S100 proteins are soluble in 100% ammonium sulfate and now considered as a member of the S100 family of calcium binding proteins those are more than 20 members of the S100 family each with special effect in signal transduction (Markowits.et al. 2014, Koh.et al. 2021). In the present bioinformatic analysis we used GSE190704 dataset. In this study, Biswas AK et al. in 2023, revealed that S100A9 inhibition significantly reduces brain relapse from osimertinib-refractory cancer cells. We analyzed their data via GEO2R. To this end 4 control samples (without treatment) and 4 test samples (with inhibitor treatment) were compared. Results demonstrated that caspase 14 (CASP14), coiled-coil domain containing 8 (CCDC8) and interleukin 20 receptor subunit beta (IL20RB) are the genes with the greatest increase in expression level. Caspases are main contributor of metastasis. CASP14 plays a role in protein maturation of filaggrin and DNA repair. Overexpression of this caspase has been reported in several epithelial malignancies. Moreover, CASP14 overexpression is significantly correlated with higher incidence of the early tumor recurrence and increasing the drug resistance (Fang.et al. 2011) CCDC8 defined as a tumor suppressor in several malignancies, such as breast, lung and prostate cancers. It is contributed to gene expression regulation, cell division, and membrane fusion and may suppress the invasion and metastasis of lung cancer cells (Jiang.et al. 2016). IL20RB is a subunit of the interleukin-20 receptor and interleukin-22 receptor. It is believed to be involved in both pro-inflammatory and anti-inflammatory responses and implicated in VEGF-mediated angiogenesis (Zhang.et al. 2022, Dayton.et al. 2021). All together resulted data revealed that inhibition of S100A9 could be effective in the reducing of cancer cell metastasis throughout the overexpression of key regulator of metastasis such as CASP14, CCDC8 and IL20RB. However, further experimental studies are necessary to validate the bioinformatic data.