The Landscape of the Tumor Microenvironment in Skin Cutaneous Melanoma Reveals a Prognostic and Immunotherapeutically Relevant Gene Signature

• DOI: 10.3389/fcell.2021.739594
• Publication Date: 2021-10-01T08:55:49Z
• Authors: Sitong Zhou; Yidan Sun; Tianqi Chen; Jingru Wang; Jia He; Jin Lyu; Yanna Shen; Xiaodong Chen; Ronghua Yang
• Keywords: Gene signature; Signature (topology)

The tumorigenesis of skin cutaneous melanoma (SKCM) remains unclear. tumor microenvironment (TME) is well known to play a vital role in the onset and progression SKCM. However, dynamic mechanisms immune regulation are insufficient. We conducted comprehensive analysis cell infiltration TME. Based on differentially expressed genes (DEGs) clusters grouped by status, set hub related clinical prognosis SKCM was explored. Methods: analyzed two independent cohorts assessed relationship between internal pattern characteristics, including clinicopathological features, potential biological pathways, gene mutations. Genes TME cells were determined. Furthermore, unsupervised clustering method (k-means) used divide samples into three different categories according TME, which defined as cluster-A, -B, -C. DEGs among groups signature genes. further distinguished common whether differences significant divided Signature gene-A group with gene-B insignificant differences. mainly had exon skipping SKCM, while no obvious alternative splicing form. Subsequently, we genetic variations signatures constructed competing endogenous RNA (ceRNA) regulatory network. LASSO Cox regression determine risk score Finally, obtained 13 calculated based coefficient each explore impact high- low-risk scores biologically functions patients further. correlation characteristics indicated that associated cluster-A classification ( p < 0.001) metastatic 0.001). Thirteen also showed prognostic effects pan-cancer. results univariate multivariate analyses revealed could be an factor for predicting patients. nomogram integrated predict survival probability regression. pan-cancers obtained. According immunohistochemistry staining results, Ube2L6 , SRPX2 IFIT2 at higher levels, CLEC4E END3 KIR2DL4 lower levels 25 specimens. Conclusion: performed assessment immune-associated To elucidate development immune-genomic features unprecedented characteristic EDN3 UBE2L6 ) landscape These prognoses drug responses can robust biomarker predictor immunotherapy effect.