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

Author:

Tang Yumei,Lei Ye,Gao Peng,Jia Junting,Du Huijun,Wang Qitong,Yan Zhixin,Zhang Chen,Liang Guojun,Wang Yanfeng,Ma Weijun,Xing Nianzeng,Cheng Le,Ren Laifeng

Abstract

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.

Funder

the Youth Project of National Natural Science Foundation of China

the Project funded by China Postdoctoral Science Foundation

the Youth Project of Natural Science Foundation of Hunan Science

the Doctoral Research Start-up Fund from Shanxi Province Cancer Hospital and Research Institute

National Key R&D Program of China

the National Natural Science Foundation of China

Yunnan High-level Talent Training Support Program, special project for industrial technology leading talents

Major Science and Technology Projects of Yunnan Province

the Key Research and Development (R&D) Projects of Shanxi Province

the Construction Project of Tumor Immunology Innovation Team of Shanxi Cancer Hospital

Publisher

Springer Science and Business Media LLC

Subject

Cancer Research,Genetics,Oncology

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