Molecular Profiling of Core Immune-Escape Genes Highlights LCK Has Potential to Reshape TME in Melanoma

Abstract

Background: The game between the immune system of the organism and the tumor is a dynamic course of events. Once the escape phase is reached, the tumor will overcome the limitations of the immune system and the tumor will progress. Objective: This study aimed to determine the potential tumor environment-based prognostic biomarkers related to immunotherapy in melanoma. Methods: 471 tumor samples and 398 normal samples were extracted from The Cancer Genome Atlas and The Genotype-Tissue Expression. Furthermore, a core set of immune-escape genes were collected from previous studies and a set of immune-related genes were obtained from IMMPORT database. Through overlapping these two sets of genes, a set of core immune-escape related genes were identified. In the next place, we conducted a systematic analysis of core immune-escape related genes through The Cancer Genome Atlas cohort and identified independent prognostic factors in melanoma. Through CIBERSORT, ssGSEA algorithm and TIMER database, we explored the potential of independent prognostic factors to reshape the tumor microenvironment.Results: Through Kaplan-Meier as well as univariate cox regression analysis of expression profiles and clinical information obtained from the TCGA cohort, we found that high LCK expression was associated with prolonged overall survival. In addition, the expression level of LCK was significantly correlated with the dysregulation of the infiltration level of immune cells in the tumor microenvironment. Conclusions: In this study, we determined LCK as a biomarker that is significantly associated with tumor environment and has significant prognostic significance. Meanwhile, immunotherapeutic approaches targeting LCK in tumor cells may provide a new perspective for the treatment of melanoma.