Pan-cancer analysis and experimental validation of DTL as a potential diagnosis, prognosis and immunotherapy biomarker

Abstract

Background DTL has been found to be related with multiple cancers. However, comprehensive analyses, which identify the prediction value of DTL in diagnosis, prognosis, immune infiltration and treatment, have rarely been reported so far. Methods Combined with the data online databases, the gene expression, gene mutation, function enrichment and the correlations with the immunity status and clinical indexes of DTL were analyzed. Expression of DTL and the degree of immune cell infiltration were examined by immunofluorescence (IF) and immunohistochemistry (IHC) and analyzed by statistical analysis. Furthermore, the influences of DTL on the cell cycle, cell proliferation and apoptosis were detected by live cell imaging, IF and flow cytometric (FC) analysis. Genomic stability assays were conducted by chromosome slide preparation. Results DTL was widely expressed in various cells and tissues, while it was overexpressed in tumor tissues except acute myeloid leukemia (LAML). Pan-cancer bioinformatics analysis showed that the expression of DTL was correlated with the prognosis, immunotherapy, and clinical indexes in various cancers. In addition, gene set enrichment analysis (GSEA) uncovered that DTL was enriched in oocyte meiosis, pyrimidine metabolism, the cell cycle, the G2M checkpoint, mTORC1 signaling and E2F targets. Furthermore, the overexpression of DTL, and its association with immune cell infiltration and clinical indexes in liver hepatocellular carcinoma (LIHC), bladder urothelial carcinoma (BLCA) and stomach adenocarcinoma (STAD) were verified in our study. It was also verified that overexpression of DTL could regulate the cell cycle, promote cell proliferation and cause genomic instability in cultured cells, which may be the reason why DTL plays a role in the occurrence, progression and treatment of cancer. Conclusions Collectively, this study suggested that DTL is of clinical value in the diagnosis, prognosis and treatment of various cancers, and may be a potential biomarker in certain cancers.

FAM60A promotes osteosarcoma development and progression

“…Additionally, on the basis of correlation analysis of the genes included in the follow‐up immunological examination, effective immunotherapy outcomes were anticipated. 43 Thus, given the significance of immunotherapy in the management of malignant tumors, targeting DTL might provide us with fresh perspectives on OS therapy. EXO1 plays a key role in protecting genome stability during DNA replication and post‐replication processes; further, it participates in and plays important roles in various DNA repair processes.…”

E3 ubiquitin ligases and deubiquitinases in bladder cancer tumorigenesis and implications for immunotherapies

“…Denticleless E3 ubiquitin protein ligase homolog (DTL) is overexpressed in BCa, and increased DTL expression correlates with malignant biological behavior and promotes BCa progression through the AKT/mTOR pathway ( 61 ). A pan-cancer study also showed that DLT could be a potential immunotherapy biomarker ( 106 ).…”