Lung cancer is the main cause of cancer death, with adenocarcinoma as the main subtype. In order to improve the prognosis of LUAD patients, it is necessary to identify new biomarkers of LUAD.(18) Our study is the first to show that the expression of emid1 is related to cancer and may be a prognostic biomarker for LUAD.
Our study confirmed that the low expression of EMID1 in LUAD is related to the poor survival time and prognosis, as well as the progress of clinical pathology such as late stage and metastasis of lung cancer. The study deployed GSEA to further explore EMID1 functionality in LUAD, and specified the following as differentially enriched in its high expression phenotype: melanogenesis, basal cell carcinoma, vasoconstriction, glycosaminoglycan biosynthesis of heparin sulfate, Notch signaling pathway, neuroactive ligand receptor interaction, hedgehog signaling pathway, ganglioside biosynthesis series, GnRH signaling pathway and dilated heart Myopathy. We also evaluated the relationship between the expression of EMID1 and the level of immune infiltration in LUAD by CIBERSORT. The expression of EMID1 has an effect on a variety of immune cells. All the results suggested that EMID1 might be an independent prognostic marker of LUAD.
Notch pathway is involved in cell proliferation, differentiation and survival. Notch signaling pathway is one of the common signaling pathways in cancer. Notch activated mutations and amplification of Notch pathway play a key role in the progression of cancer. (20) Notch signaling pathway is a highly conserved ligand receptor signaling pathway, which contains four Notch receptors and five ligands. The four receptors are notch 1, notch 2, notch 3 and notch 4, which have similar structures.(21–23) Anja Baumgart et al. found that the lack of Notch 1 led to the reduction of early tumor formation, suggesting that notch 1 plays a role in promoting cancer. However, the expression of notch 2 receptor in NSCLC is weak, suggesting that notch 2 may play an anti-cancer role in NSCLC.(24) Compared with notch 1 and 2, notch 3 receptor has received less attention, but its role can not be ignored. Min Zhou et al. showed that the activation of Notch 3 can promote the development of lung cancer, suggesting that Notch 3 may be a carcinogen of lung cancer.(25) Therefore, we speculated that the increased expression of emid1 might play an anti-cancer role by inhibiting the activity of Notch 1 and notch 2, or by stimulating the activity of notch 2. In a word, through the study of biological function, we can further understand the function of EMID1.
Tumor infiltrating lymphocyte, as a primary prognostic biomarker in tumor progression, can also serve to independently predict sentinel lymph node status and survival in cancer.(26, 27) A significant aspect of our study entailed EMID1 expression with reference to immune infiltration levels in LAUD, and concluded a positive correlation with B cells, thereby indicating EMID1 regulated tumor immunology. Research evidence increasingly submits tumor-infiltrating B cells correlate with positive clinical outcomes in several cancers, producing antibodies whilst also acting as APCs or antigen presenting cells that intrinsically regulate cellular immunity in a tumor microenvironment.(28–30) Moreover, B cells also have the opposite effect on tumor immunity and progression. For example, B cells regulate adaptive immunity by releasing circulating cytokines or chemokines, thereby recruiting immunosuppressive myeloid cells, which eventually lead to chronic inflammation or neonatal cancer.(31) Kuo-Hao. et al. also correlated B cell infiltration with anti-PD-L1 therapy to potentially advance prospective treatment options for lung cancer patients.(32) However, the mechanism of EMID1 regulating tumor-infiltrating B cells are not clear, and more research is needed.
Our study still has several shortcomings. First of all, the clinical data types of our samples were less, which inevitably leads to the loss of some useful information. Secondly, our study did not analyze the signal mechanism at the cytological level. Finally, this study did not carry out protein level analysis because there was not enough clinical sample data. In a word, our conclusions still require validation via an expanded clinical sampling in future research.
In conclusions, our study assessed the relationship between EMID1 and clinicopathologic variables and survival outcomes and explored the mechanism of EMID1 in lung adenocarcinoma. Notch signaling pathway may be the main regulation pathway of EMID1 in LUAD. In addition, the change of EMID1 expression was related to the proportion of B cells in LUAD, EMID1 may play an important role in the immune environment of LUAD. Therefore, EMID1 may be a promising prognostic marker for lung adenocarcinoma.