Data Sheet 3_High expression of SOX10 is correlated with poor prognosis and immune infiltrates in skin cutaneous melanoma.xlsx

BackgroundSkin Cutaneous Melanoma (SKCM) is a malignant tumor and the prediction of its prognosis remains challenging. Sex determining region Y-box 10 (SOX10) is over-expressed in SKCM and reported to accelerate tumor invasion and immunosuppression. Although studies have suggested the correlation of immune infiltration between SOX10 and SKCM, further in-depth explore of the immunomodulatory role of SOX10 is still needed. Therefore, we assessed the prognostic role of SOX10 and its correlation with immune infiltration and checkpoint expression.
MethodsRNA sequencing data were obtained for analysis of SOX10 expression and differentially expressed genes (DEGs) from the Cancer Genome Atlas (TCGA). Moreover, functional enrichment analysis of SOX10-related DEGs was performed by GO/KEGG, GSEA. Receiver operating characteristic (ROC) curves were used to assess the diagnostic value of SOX10 in SKCM. Kaplan-Meier method was conducted to assess the effect of SOX10 on survival. Additionally, the clinical significance of SOX10 in SKCM was figured out by LASSO and prognostic nomogram model. We analyzed SOX10-related immune cell infiltration and expression of immune checkpoints. Finally, validations were performed through immunohistochemical analysis.
ResultsSOX10 was low expressed in a range of malignant tumor tissues except SKCM. Totally, 1029 differentially significant genes (DSGs) were identified between SOX10 low- and high- expression group, of which 50 genes were upregulated and 979 genes were downregulated. Additionally, SOX10 high expression was remarkably associated with pathologic stage, age and breslow depth in a sample of 472 cases (P < 0.05). Screening was performed by LASSO coefficients to select non-zero variables that satisfied the coefficients of lambda, and 8 genes were screened out. The forest plot results showed that only OCA2 and TRAT1 had statistical significance (P < 0.05) by multi-factor COX regression analysis. SOX10, OCA2, TRAT1, pathologic stage, age and breslow depth were included in the nomogram prognostic model. Furthermore, upregulation of SOX10 expression inhibited immune infiltration in SKCM.
ConclusionOverall, high expression of SOX10 was correlated with poor prognosis in SKCM, which may be related to suppression of immune infiltration. The DSGs and pathways identified in our research have initially provided an insight into the molecular mechanisms underlying the progression of SKCM.

背景 皮肤黑色素瘤（Cutaneous Melanoma, SKCM）是一种恶性肿瘤，其预后预测仍具挑战性。性别决定区Y框蛋白10（Sex determining region Y-box 10, SOX10）在SKCM中呈过表达状态，据报道可促进肿瘤侵袭与免疫抑制。尽管已有研究提示SOX10与SKCM免疫浸润存在相关性，但仍需进一步深入探究其免疫调节作用。为此，本研究评估了SOX10的预后价值，及其与免疫浸润、免疫检查点表达的相关性。

方法 从癌症基因组图谱（The Cancer Genome Atlas, TCGA）获取RNA测序数据，用于分析SOX10的表达水平及差异表达基因（Differentially Expressed Genes, DEGs）。此外，通过GO/KEGG富集分析、基因集富集分析（Gene Set Enrichment Analysis, GSEA）对SOX10相关差异表达基因开展功能富集分析。采用受试者工作特征曲线（Receiver Operating Characteristic curve, ROC）评估SOX10对SKCM的诊断价值。采用Kaplan-Meier法分析SOX10对患者生存的影响。此外，通过最小绝对收缩和选择算子（Least Absolute Shrinkage and Selection Operator, LASSO）及预后列线图模型，明确SOX10在SKCM中的临床意义。本研究还分析了SOX10相关免疫细胞浸润情况及免疫检查点的表达水平。最后，通过免疫组化分析完成验证。

结果 除SKCM外，SOX10在多种恶性肿瘤组织中呈低表达。共筛选得到1029个SOX10高低表达组间的差异显著基因（Differentially Significant Genes, DSGs），其中50个基因上调，979个基因下调。在472例样本中，SOX10高表达与病理分期、年龄及布雷斯洛深度（Breslow depth）显著相关（P < 0.05）。通过LASSO系数筛选满足lambda系数的非零变量，最终得到8个候选基因。森林图（Forest Plot）结果显示，经多因素COX回归分析，仅OCA2与TRAT1具有统计学意义（P < 0.05）。将SOX10、OCA2、TRAT1、病理分期、年龄及布雷斯洛深度纳入列线图预后模型。进一步研究发现，SOX10表达上调可抑制SKCM中的免疫浸润。

结论 总体而言，SOX10高表达与SKCM不良预后密切相关，其潜在机制可能与免疫浸润抑制有关。本研究鉴定的差异显著基因及通路，为阐明SKCM进展的分子机制提供了初步的理论依据与研究视角。