Identification of CXCL13 as an Immune-Related Biomarker Associated with Tumorigenesis and Prognosis in Cutaneous Melanoma Patients

Abstract

Background Melanoma is one of the most lethal tumors and its treatment is still challenging. It is urgent to detect novel therapy targets in melanoma. Material/Methods The GEO dataset was used to obtain a list of DEGS (differentially-expressed genes). Integrative bioinformatics analyses, including HPRD database, TCGA data, and TIMER, were performed to determine the role of CXCL13 in SKCM (skin cutaneous melanoma) progression and the immune environment. Furthermore, Pearson correlation coefficient analysis was used to measure correlations between CXCL13 and its co-expressed genes. Survival analysis, GO, and KEGG enrichment analysis were performed to investigate the role of CXCL13 in SKCM. Results A total of 41 DEGs were identified in 3 GEO datasets, and 4 out of 41 DEGs are hub genes. Among the 4 hub genes, CXCL13 is involved in the most KEGG terms. CXCL13 is co-expressed with well-known immune checkpoint blockade targets, and it was associated with better overall survival. In addition, CXCL13 levels in infiltrating immune cells (neutrophil and myeloid dendritic cells) affect prognosis and survival in SKCM. Functional enrichment analysis clarified that CXCL13- co-expressed top 30 genes were associated with immune signaling pathways. Network analysis identified CXCL13 as a hub gene that interacts with CXCR5 to participate in immune-related biological process. Conclusions This study found that CXCL13 is associated with SKCM tumorigenesis and prognosis and immune infiltrations. Our result suggests that CXCL13 has great potential in development of novel immunotherapy targets in melanoma.

CDCA3 is a prognostic biomarker for cutaneous melanoma and is connected with immune infiltration

“…In addition, appropriate biomarkers should enable not only monitoring of the disease progression and response to treatment but also the early identification of individuals at high risk of metastases who may benefit from closer surveillance and adjuvant medicines (18,23). A study reported by Huang and Han et al primarily identified five chemokine members (CCL4, CCL5, CXCL9, CXCL10, CXCL13) as relevant biomarkers in cutaneous melanoma tumorigenesis and progression (24). Alimohammadi et al revealed that CXCR4 is implicated in the progression and metastasis of cutaneous melanoma (25).…”

“…A study reported by Huang and Han et al. primarily identified five chemokine members (CCL4, CCL5, CXCL9, CXCL10, CXCL13) as relevant biomarkers in cutaneous melanoma tumorigenesis and progression ( 24 ). Alimohammadi et al.…”

The Prognostic and Predictive Role of Xeroderma Pigmentosum Gene Expression in Melanoma

“…Correspondingly, in our univariate analysis with segregated parameters for high and low values based on medians, we found no difference between TMB groups (Table S11). CXCL13 was suggested as a prognostic biomarker in melanoma before, but the correlation of ERCC3 with survival needs further validation (78,79).…”

Predicting patient outcomes after treatment with immune checkpoint blockade: A review of biomarkers derived from diverse data modalities

“… 7 For ICB outcome prediction, the expression levels of genes associated with immune response mechanisms, from prior knowledge of cancer immunology, are commonly used. Those genes include known ICB targets ( CTLA4 , PD-1 , and PD-L1 ), cytokines and chemokines, 8 , 9 , 10 and genes involved in neoantigen presentation and immune-related biological pathways. 11 , 12 However, those genes have varied predictive effectiveness due to the large extent of inter- and intra-tumor heterogeneity and the complexity of the immune system.…”