Abstract
Skin cutaneous melanoma (SKCM) is a skin cancer type characterized by a high degree of immune cell infiltration. The potential function of lactate, a main metabolic product in the tumor microenvironment (TME) of SKCM, remains unclear. In this study, we systemically analyzed the predictive value of lactate-related genes (LRGs) for prognosis and response to immune checkpoint inhibitors (ICIs) in SKCM patients included from The Cancer Genome Atlas (TCGA) database. Cluster 3, by consensus clustering for 61 LRGs, manifested a worse clinical outcome, attributed to the overexpression of malignancy marks. In addition, we created a prognostic prediction model for high- and low-risk patients and verified its performance in a validation cohort, GSE65904. Between TME and the risk model, we found a negative relation of the immunocyte infiltration levels with patients’ risk scores. The low-risk cases had higher ICI expression and could benefit better from ICIs relative to the high-risk cases. Thus, the lactate-related prognosis risk signature may comprehensively provide a basis for future investigations on immunotherapeutic treatment for SKCM.
Highlights
Skin cutaneous melanoma (SKCM) is more aggressive than other skin cancer types owing to its rapid progression, poor prognosis, and high mortality [1]
A total of 184 lactate-related genes (LRGs) were obtained from the Molecular Signatures Database (INCREASED SERUM LACTATE, M35671, http:// www.gsea-msigdb.org/gsea/index.jsp) [18]
The most significant module was identified using the MCODE algorithm (Supplementary Figure 1). The functions of these 61 differentially expressed LRGs were predicted, and the results of the Gene Ontology (GO) annotation indicated these were markedly augmented in energy metabolism-related processes, including the Lactate and Immunotherapy in SKCM B
Summary
Skin cutaneous melanoma (SKCM) is more aggressive than other skin cancer types owing to its rapid progression, poor prognosis, and high mortality [1]. The cases invasive melanoma account for ~5% of all skin malignant tumors, it causes >75% of skin cancer-related deaths. The fiveyear survival rates in localized or regional melanoma are 98% and 64%, respectively, these rates reduce to 23% in the advanced stages [2], thereby illustrating that early intervention to prevent the disease from metastasizing is essential for improving the clinical prognoses. Surgery is the most effective curative strategy, while for the metastatic cases, systemic treatment plays a significant role in inhibiting further disease progression [3]. Immunotherapy has emerged as the most promising treatment modality against several tumor types.
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