Comprehensive analysis of cyclin-dependent kinase 6 and its correlation with immune infiltration in uterine corpus endometrial carcinoma

Background: CDK6, a member of the cyclin-dependent kinases (CDKs) family, is known as a classic cell cycle regulating kinases and plays an important role in promoting cancer initiation as well as progression. However, how CDK6 affects the immune system and the prognosis of uterine corpus endometrial carcinoma(UCEC) remains to be determined. Methods: : TIMER, UALCAN, TCGA, HPA, LinkedOmics, STRING, cBio-Portal and COSMIC were used to analyze the expression and mutation of CDK6 in patients with UCEC and its clinical value, and to explore the possible mechanism of CDK6 in the occurrence and development of UCEC through the biological functional analysis and immune infiltration. Results: : Our results suggested that the overall expression level of CDK6 in UCEC was significantly lower than that in adjacent normal tissues. Inversely, the CDK6 level in the intermediate-/high-risk endometrial carcinoma group was significantly higher than patients in the low-risk group. Subgroup analysis showed that the serous histological type, grade 3, and stage III had significantly higher CDK6 levels. The result of promoter methylation analysis served as a good explanation of the above conclusion. What’s more, patients with high CDK6 expression had a poorer prognosis compared with those patients with low CDK6 expression using the ULCAN and Kaplan–Meier plotter data analysis. GO and KEGG enrichment analysis revealed that the Gene Co-Expression Network of CDK6 was mainly involved in extracellular structure organization and focal adhesion. PPI analysis validated that CDK6 was controlled by the Cip/Kip family and the INK4 family. Importantly, we found that CDK6 was significantly correlated with most of the immune markers of different T cells in UCEC, which suggested that CDK6 plays an important role in regulating UCEC tumor immunity and is probably involved in the T cell immune response. In addition, M1, M2 macrophage, TAM, Monocyte, Neutrophil, and Dendritic cell were also verified to correlate with CDK6 significantly. Conclusions: : CDK6 plays an important role in endometrial carcinoma progression and may serve as a potential prognostic biomarker and novel risk stratification target for endometrial carcinoma.