TNFSF10, an autophagy related gene, was a prognostic and immune infiltration marker in skin cutaneous melanoma

Abstract

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.

Identification and verification of a prognostic autophagy-related gene signature in hepatocellular carcinoma

“…Tumour necrosis factor-related apoptosis-inducing ligand 10 (TNFSF10) is a death ligand cytokine that is mainly expressed by effector immune cells to kill malignantly transformed cells 32 . As an autophagy gene, TNFSF10 has the potential to predict the prognosis of melanoma patients and serve as a therapeutic marker for melanoma 33 . TNFSF10 is downregulated in HCC and may serve as a potential therapeutic target for HCC 34 .…”

Identification of the role of autophagy-related TNFSF10/ hsa-let-7a-5p axis in vitiligo development and potential herbs exploring based on a bioinformatics analysis

“…As reported, TNFSF10 is a promising anticancer agent for treating solid tumors, which has the unique property of inducing apoptosis in tumor cells while sparing normal ones [ [56] , [57] , [58] ]. It has also been reported that TNFSF10 was able to induce autophagy in certain cancer cells, however, how TNFSF10 induces autophagy has not been clearly elucidated [ 59 ]. MAPK8 activation mediated by TRAF2 and RIPK1 might be crucial for TNFSF10-induced autophagy [ 60 ].…”