Development and Validation of a CD8+ T Cell Infiltration-Related Signature for Melanoma Patients

Abstract

AimImmunotherapy shows efficacy in only a subset of melanoma patients. Here, we intended to construct a risk score model to predict melanoma patients’ sensitivity to immunotherapy.MethodsIntegration analyses were performed on melanoma patients from high-dimensional public datasets. The CD8+ T cell infiltration related genes (TIRGs) were selected via TIMER and CIBERSORT algorithm. LASSO Cox regression was performed to screen for the crucial TIRGs. Single sample gene set enrichment analysis (ssGSEA) and ESTIMATE algorithm were used to evaluate the immune activity. The prognostic value of the risk score was determined by univariate and multivariate Cox regression analysis.Results184 candidate TIRGs were identified in melanoma patients. Based on the candidate TIRGs, melanoma patients were classified into three clusters which were characterized by different immune activity. Six signature genes were further screened out of 184 TIRGs and a representative risk score for patient survival was constructed based on these six signature genes. The risk score served as an indicator for the level of CD8+ T cell infiltration and acted as an independent prognostic factor for the survival of melanoma patients. By using the risk score, we achieved a good predicting result for the response of cancer patients to immunotherapy. Moreover, pan-cancer analysis revealed the risk score could be used in a wide range of non-hematologic tumors.ConclusionsOur results showed the potential of using signature gene-based risk score as an indicator to predict melanoma patients’ sensitivity to immunotherapy.

Core immune cell infiltration signatures identify molecular subtypes and promote precise checkpoint immunotherapy in cutaneous melanoma

“…Previous studies suggested that NK cell-related signature, CD8 + T cell-related signature, PD-L1 expression, or TMB could be used to predict the prognosis of CM patients (14,32,33). The cTICscore, compared with these predictors, seemed to have better predictability based on the AUC of the time-dependent ROC curves (Figure 1C).…”

“…CM patients stratified into two subgroups using the median cTICscore as the cutoff value showed distinct prognosis in all the three datasets and the external validating GSE54467 ( Figure 1B ). Previous studies suggested that NK cell–related signature, CD8 + T cell-related signature, PD-L1 expression, or TMB could be used to predict the prognosis of CM patients ( 14 , 32 , 33 ). The cTICscore, compared with these predictors, seemed to have better predictability based on the AUC of the time-dependent ROC curves ( Figure 1C ).…”

“…The downloading and processing of the data of CM patients from the Cancer Genome Atlas (TCGA_SKCM) database was conducted as reported in our previous study (14). Normalized gene expression data and clinical data of datasets from the Gene Expression Omnibus (GEO) database (GSE65904, GSE22153, GSE54467, GSE100797, GSE35640, and GSE176307) were acquired via the GEOquery package in R software or from the supplementary files of the corresponding publications (15)(16)(17)(18)(19)(20).…”

Development and Validation of Tumor Immunogenicity Based Gene Signature for Skin Cancer Risk Stratification

“…Guanylate-binding protein 4(GBP4) belongs to the interferon-stimulated factor that acts as a protective factor in host defense, and several genes from the GBP family act as tumor suppressors [ 27 , 28 ]. In addition, a recent study found the GBP4 was positively correlated with immune cell infiltration in melanoma patients [ 29 ]. Docking protein-1 (DOK1), a tumor suppressor, is frequently downregulated in human tumors such as ovarian cancer, Burkitt lymphoma, head and neck cancer (HNC), chronic lymphocytic leukemia (CLL), lung cancer, and breast cancer [ 30 , 31 ].…”

Downregulation of NEDD4L by EGFR signaling promotes the development of lung adenocarcinoma

“…C2.cp.k egg.v7.1.symbols.gmt was chosen as the gene set database. Signaling pathways that meet the following criteria can be significantly enriched: nominal p-value < 0.05, q-value < 0.25, and normalized enrichment score > 1 [ 27 ].…”