MLK4 as an immune marker and its correlation with immune infiltration in Cervical squamous cell carcinoma and endocervical adenocarcinoma(CESC)

Abstract

AbstractMixed pedigree kinase 4 (MLK4) is a member of the serine/threonine kinases mixed pedigree kinase (MLKs) family. Few reports on immune-related targets in Cervical squamous cell carcinoma and endocervical adenocarcinoma CESC, and the role of MLK4 in cervical cancer remains to be studied. The expression of MLK4 in CESC was analyzed by TCGA database, and the effect of MLK4 on immune invasion was evaluated. Tissue microarray was used to verify the expression of MLK4 in CESC patients, and it was found that MLK4 was significantly overexpressed in CESC, and significantly correlated with CESC grade. Multiple analysis algorithms showed that the high expression of MLK4 was negatively correlated with immune cell infiltration in CESC. Analysis showed that MLK4 expression was negatively correlated with the infiltration of various immune cells including CD8 + T cells, and MLK4 mRNA expression was positively correlated with immune checkpoints PD-L1,CTLA4, LAG3, and negatively correlated with immune promotion genes CD86 and CD80. Furtherly, In vitro assays were conducted to identify the biological behavior of MLK4 in C33A cells. The downregulation of MLK4 resulted in reduced cell proliferation and invasion in C33A cells, as revealed by the EDU and transwell assays. QPCR results show that knock down MLK4 would inhibit the expression of classical biochemical markers CEA、AFP and HCG. Therefore, MLk4 may play a critical role in Cervical cancer.