Pan-cancer analysis and experimental validation of DTL as a potential diagnosis, prognosis and immunotherapy biomarker.
Pan-cancer analysis and experimental validation of DTL as a potential diagnosis, prognosis and immunotherapy biomarker.
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DOI：
10.1186/s12885-023-10755-z
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发表时间：
2023-04-10
期刊：
影响因子：
3.8
通讯作者：
中科院分区：
文献类型：
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DTL已被发现与多种癌症有关。然而，迄今为止，对DTL在诊断、预后、免疫浸润和治疗方面的预测价值进行全面分析的报道很少。结合在线数据库数据，分析DTL的基因表达、基因突变、功能富集及其与免疫状态和临床指标的相关性。采用免疫荧光法（IF）、免疫组化法（IHC）检测DTL表达及免疫细胞浸润程度，并进行统计学分析。通过活细胞成像、IF和流式细胞术（FC）检测DTL对细胞周期、细胞增殖和凋亡的影响。基因组稳定性测定采用染色体载玻片制备。DTL在多种细胞和组织中广泛表达，在除急性髓系白血病（LAML）外的肿瘤组织中均有过表达。泛癌生物信息学分析显示，DTL的表达与多种肿瘤的预后、免疫治疗及临床指标相关。此外，基因集富集分析（GSEA）发现DTL富集于卵母细胞减数分裂、嘧啶代谢、细胞周期、G2M检查点、mTORC1信号通路和E2F靶点。此外，我们的研究证实了DTL在肝细胞癌（LIHC）、膀胱尿路上皮癌（BLCA）和胃腺癌（STAD）中的过表达及其与免疫细胞浸润和临床指标的关系。我们也证实过表达DTL可以调节细胞周期，促进细胞增殖，并在培养细胞中引起基因组不稳定，这可能是DTL在癌症的发生、发展和治疗中发挥作用的原因。综上所述，本研究提示DTL在各种癌症的诊断、预后和治疗中具有临床价值，可能是某些癌症的潜在生物标志物。在线版本包含补充材料，可在10.1186/s12885-023-10755-z获得。
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. 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. 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. 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. The online version contains supplementary material available at 10.1186/s12885-023-10755-z.
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影响因子：
7.3
作者：
Li Z;Wang R;Qiu C;Cao C;Zhang J;Ge J;Shi Y
通讯作者：
Shi Y
DOI：
10.1056/nejmoa1003466
发表时间：
2010-08-19
期刊：
The New England journal of medicine
影响因子：
--
作者：
Hodi FS;O'Day SJ;McDermott DF;Weber RW;Sosman JA;Haanen JB;Gonzalez R;Robert C;Schadendorf D;Hassel JC;Akerley W;van den Eertwegh AJ;Lutzky J;Lorigan P;Vaubel JM;Linette GP;Hogg D;Ottensmeier CH;Lebbé C;Peschel C;Quirt I;Clark JI;Wolchok JD;Weber JS;Tian J;Yellin MJ;Nichol GM;Hoos A;Urba WJ
通讯作者：
Urba WJ
影响因子：
16
作者：
Abbas T;Shibata E;Park J;Jha S;Karnani N;Dutta A
通讯作者：
Dutta A
影响因子：
11.5
作者：
Georgiadis, Andrew;Durham, Jennifer N.;Sausen, Mark
通讯作者：
Sausen, Mark
影响因子：
16
作者：
Ciccia A;Elledge SJ
通讯作者：
Elledge SJ