Xue Lei, Zhang Wancong, Ju Yikun, Xu Xuezheng, Bo Hao, Zhong Xiaoping, Hu Zhexiao, Zheng Congyuan, Fang Bairong, Tang Shijie
Department of Pathology, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China.
Department of Plastic Surgery and Burn Center, Second Affiliated Hospital, Shantou University Medical College, Shantou, Guangdong, China.
J Cancer. 2023 Jul 31;14(13):2417-2430. doi: 10.7150/jca.86735. eCollection 2023.
Autophagy exerts a pivotal effect on skin cutaneous melanoma (SKCM). This study was aimed to investigate the expression of autophagy related genes (ARGs) in SKCM as well as its clinical value. Differentially expressed (DE) ARGs were downloaded from the intersection of SKCM data in GEPIA2 database and ARGs in Human Autophagy Database (HADB) database, and were verified in SKCM datasets GSE46517 and GSE15605. DE ARGs were enriched by Metascape online tools. According to GEPIA2 database, tumor necrosis factor-related apoptosis-inducing ligand (TNFSF10) was identified as a closely related factor and prognostic marker of SKCM. Then the correlation analysis of clinicopathological characteristics between TNFSF10 and SKCM was completed by several online tools such as TISCH, HPA, BEST and qRT-PCR. Subsequently, we investigated TNFSF10 related functions and signal pathways with LinkedOmics online tool, and immune infiltration using Assistant for Clinical Bioinformatics online tool. Furthermore, correlation analysis between TNFSF10 expression and immunotherapy response was performed by TIDE algorithm and BEST online tool. And Kaplan-Meier Plotter was used to assessing the prognosis of SKCM patients receiving immunotherapy. Finally, the correlation analysis among TNFSF10 methylation, TNFSF10 expression and patient prognosis was completed by the DiseaseMeth version 2.0, UCSC XENA and qRT-PCR. ARGs are DE in SKCM and participate in the ERBB signaling pathway, as well as the processing and presentation of antigens. Moreover, TNFSF10's expression along with methylation expression were significantly associated with the prognosis. Low expression of TNFSF10 was associated with malignant clinicopathological features, lower immune signal activity and lower immunocytes abundance in patients with SKCM. As an ARG, TNFSF10 has a potential capacity in predicting the prognosis of SKCM patients, meanwhile, may be a novel immunotherapy marker for SKCM.
自噬在皮肤黑色素瘤（SKCM）中发挥着关键作用。本研究旨在调查自噬相关基因（ARG）在SKCM中的表达及其临床价值。从GEPIA2数据库中的SKCM数据与人类自噬数据库（HADB）数据库中的ARG的交集下载差异表达（DE）的ARG，并在SKCM数据集GSE46517和GSE15605中进行验证。通过Metascape在线工具对DE ARG进行富集。根据GEPIA2数据库，肿瘤坏死因子相关凋亡诱导配体（TNFSF10）被确定为SKCM的密切相关因子和预后标志物。然后通过TISCH、HPA、BEST和qRT-PCR等几种在线工具完成TNFSF10与SKCM之间临床病理特征的相关性分析。随后，我们使用LinkedOmics在线工具研究TNFSF10相关功能和信号通路，并使用临床生物信息学助手在线工具进行免疫浸润分析。此外，通过TIDE算法和BEST在线工具进行TNFSF10表达与免疫治疗反应之间的相关性分析。并使用Kaplan-Meier Plotter评估接受免疫治疗的SKCM患者的预后。最后，通过DiseaseMeth版本2.0、UCSC XENA和qRT-PCR完成TNFSF10甲基化、TNFSF10表达与患者预后之间的相关性分析。ARG在SKCM中存在差异表达，并参与ERBB信号通路以及抗原的加工和呈递。此外，TNFSF10的表达以及甲基化表达与预后显著相关。TNFSF10低表达与SKCM患者的恶性临床病理特征、较低的免疫信号活性和较低的免疫细胞丰度相关。作为一种ARG，TNFSF10具有预测SKCM患者预后的潜在能力，同时可能是SKCM的一种新型免疫治疗标志物。
