High MICAL1 expression correlates with cancer progression and immune infiltration in renal clear cell carcinoma

Background: Molecule interacting with CasL 1 (MICAL1), a multidomain flavoprotein monooxygenase, is strongly involved in the biological processes related to cancer cell proliferation and metastasis. However, there were few reports on the clinical significance of MICAL1 in renal clear cell carcinoma.

Methods: The expression and prognostic value of MICAL1 in renal clear cell carcinoma were explored using immunohistochemical assays, public TCGA-KIRC databases and multiple analysis methods, including survival analysis, univariate and multivariate analyses, KEGG and GSEA. Wound healing and Transwell assays were performed to check the 786-O cell and Caki-1 cell migration abilities after knockdown of MICAL1. Western blotting was used to assess the regulatory effect of MICAL1 on the Rac1 activation. Additionally, the function of MICAL1 and the correlations between MICAL1 and immune infiltration levels in KIRC were investigated using TIMER and TISIDB.

Results: MICAL1 expression was significantly higher in carcinoma tissue compared with non-cancerous tissue. A survival analysis revealed that patients with high MICAL1 expression had shorter overall survival (OS) and disease-specific survival (DSS) compared with patients with low MICAL1 expression. ROC analysis also confirmed that MICAL1 has a high diagnostic value in KIRC. Importantly, the univariate and multivariate Cox analysis further confirmed that high MICAL1 expression was an independent risk factor for OS in patients with KIRC. In accordance with this, knockdown of MICAL1 expression decreased Rac1 activation and cell migration. KEGG and GSEA analysis revealed that the immune infiltration and Ras signaling pathways were significantly upregulated in the high MICAL1 expression group. In terms of immune infiltrating levels, MICAL1 expression was positively associated with CD8+/Treg cell infiltration levels. Specifically, bioinformatic analysis showed that MICAL1 expression had strong relationships with various T cell exhaustion markers.

Conclusions: MICAL1 expression may act as a prognostic biomarker for determining the prognosis in renal clear cell carcinoma and plays an important role in regulating tumor immune microenvironment and cell migratory capacity.