Identification of Immune Function-Related Subtypes in Cutaneous Melanoma

Abstract

Tumour immunotherapy combined with molecular typing is a new therapy to help select patients. However, molecular typing algorithms related to tumour immune function have not been thoroughly explored. We herein proposed a single sample immune signature network (SING) method to identify new immune function-related subtypes of cutaneous melanoma of the skin. A sample-specific network and tumour microenvironment were constructed based on the immune annotation of cutaneous melanoma samples. Then, the differences and heterogeneity of immune function among different subtypes were analysed and verified. A total of 327 cases of cutaneous melanoma were divided into normal and immune classes; the immune class had more immune enrichment characteristics. After further subdividing the 327 cases into three immune-related subtypes, the degree of immune enrichment in the “high immune subtype” was greater than that in other subtypes. Similar results were validated in both tumour samples and cell lines. Sample-specific networks and the tumour microenvironment based on immune annotation contribute to the mining of cutaneous melanoma immune function-related subtypes. Mutations in B2M and PTEN are considered potential therapeutic targets that can improve the immune response. Patients with a high immune subtype can generally obtain a better immune prognosis effect, and the prognosis may be improved when combined with TGF-β inhibitors.

Defining Melanoma Immune Biomarkers—Desert, Excluded, and Inflamed Subtypes—Using a Gene Expression Classifier Reflecting Intratumoral Immune Response and Stromal Patterns

“…Wide exploratory studies addressing the immune aspects of melanoma TME were mostly solely computational [43][44][45], yet often meticulous and conclusive. The conventional and more supervised approaches, like ours, taking advantage of publicly available transcriptomic datasets also existed [46,47]; however, they usually carried different subtype annotations for what we believe could be recognized as immune desert, excluded, and inflamed tumors based on their biological information. Reports adopting the desert, excluded, inflamed nomenclature in melanoma were only histology based [48][49][50].…”

Network-based molecular subtyping of acral melanoma

“…Up to now, some works have been carried out on molecular typing of cutaneous melanoma. Liu et al [9] proposed a single-sample immune signature network and identified an immune-related subtype based on hierarchical clustering of transcriptome data. The immune-related subtype were further subdivided into three subtype, one of which have the highest degree of immune infiltration and generally have better outcomes after immunotherapy.…”