Abstract
Melanoma is the most dangerous type of skin cancer and has highly heterogeneous features. Despite progress in melanoma classification, interpatient heterogeneity remains difficult to predict, especially in terms of long-term survival. Here, based on mRNA-seq, miRNA-seq and DNA methylation data from 447 cutaneous melanoma patients in the Cancer Genome Atlas, we performed integrative and single-dataset clustering analyses. A novel group of patients was identified, including 301 with better, 55 with poorer and 91 with intermediate prognoses. Immune genes were upregulated in the better prognostic group, and higher immune scores (representing a greater extent of immune cell infiltration into tumor tissues) were associated with better prognoses. Higher expression of 115 genes was determined to predict better outcomes. The better prognostic group also exhibited DNA hypomethylation, and immune pathways were enriched among the hypomethylated genes. Using exome-seq data from the same patients, we observed that the better prognostic group harbored the highest number of mutations. The mutational signature in the better prognostic group was associated with ultraviolet light exposure. These integrated investigations have potential therapeutic significance, as they clarify the molecular heterogeneity of cutaneous melanoma and enhance its classification.
Highlights
Skin cancer is the most commonly occurring type of cancer
Melanoma is highly heterogeneous on the genetic, expression, and epigenetic levels [18]
Rapid advancements in understanding this heterogeneity have enabled the molecular classification of melanoma and personalized medicine for its management [9,10,11,12, 17]
Summary
Skin cancer is the most commonly occurring type of cancer. Nonmelanoma skin cancer, the most prevalent form, includes two main histological subtypes: basal cell and squamous cell carcinoma [1]. On the other hand, originates in melanocytes, the skin cells that produce melanin. The most common subtypes of melanoma are cutaneous and uveal [1]. Though melanoma represents only 4% of skin cancer cases, it exhibits the most aggressive, complex and heterogeneous features among skin cancers [2], and accounts for more than 75% of skin cancer-related deaths worldwide [3]. Over the past few decades, the incidence of cutaneous melanoma has risen by ~3% per year in the United States [4]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
