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Analysis of immune subtypes based on immunogenomic profiling identifies prognostic signature for cutaneous melanoma.

Abstract：

:Skin cutaneous melanoma (SKCM) is the most invasive form of skin cancer with poor prognosis. Growing evidence has demonstrated that tumor immune microenvironment plays a key contributing role in tumorigenesis and predicting clinical outcomes. The aim of this study was to recognize immune classification and a reliable prognostic signature for patients with SKCM. By using single-sample gene set enrichment (ssGSEA) and hierarchical clustering analyses, we evaluated the immune infiltration landscape of SKCM afflicted patients from The Cancer Genome Atlas (TCGA) dataset and named two SKCM subtypes: Immunity-high and Immunity-low. The Immunity-high subgroup was characterized by up-regulation of immune response and favorable survival probability. Seven candidate small molecule drugs which potentially reverse SKCM immune status were identified by using Connectivity map (CMap) database. A prognostic five-immune-associated gene (IAG) signature consisting IFITM1, TNFSF13B, APOBEC3G, CCL8 and KLRK1 with high predictive value was established using the LASSO Cox regression analysis in training set, and validated in testing set as well as Gene Expression Omnibus (GEO) external validation cohort (P < 0.05). Lower tumor purity and active immune-related signaling pathways were obviously presented in low-risk group. Furthermore, a novel composite nomogram based upon the five-IAG signature and other clinical parameters was built with excellent calibration curves. Collectively, comprehensively characterizing the SKCM subtypes based upon immune microenvironment landscape and development of a survival-related IAG signature may provide a promising avenue for improving individualized treatment design and prognosis prediction for patients with SKCM.

journal_name

Int Immunopharmacol

journal_title

International immunopharmacology

authors

Hu B,Wei Q,Zhou C,Ju M,Wang L,Chen L,Li Z,Wei M,He M,Zhao L

doi

10.1016/j.intimp.2020.107162

subject

Has Abstract

pub_date

2020-12-01 00:00:00

pages

107162

issue

Pt A

eissn

1567-5769

issn

1878-1705

pii

S1567-5769(20)33629-8

journal_volume

89

pub_type

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