Wang Hehe, Zhang Junge
Department of Otolaryngology, Head and Neck Surgery, Ningbo First Hospital, Ningbo, Zhejiang, People's Republic of China.
Department of Anesthesiology, Ningbo First Hospital, Ningbo, Zhejiang, People's Republic of China.
Int J Gen Med. 2022 Mar 2;15:2329-2345. doi: 10.2147/IJGM.S352330. eCollection 2022.
Although considerable progress has been made in basic and clinical research on nasopharyngeal carcinoma (NPC), the biomarkers of the progression of NPC have not been fully studied and described. This study was designed to identify potential novel biomarkers for NPC using integrated analyses and explore the immune cell infiltration in this pathological process.
Five GEO data sets were downloaded from gene expression omnibus database (GEO) and analysed to identify differentially expressed genes (DEGs), followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. The four algorithms were adopted for screening of novel and key biomarkers for NPC, including random forest (RF) machine learning algorithm, least absolute shrinkage and selection operator (LASSO) logistic regression, support vector machine-recursive feature elimination (SVM-RFE), and weighted gene co-expression network analysis (WGCNA). Lastly, CIBERSORT was used to assess the infiltration of immune cells in NPC, and the correlation between diagnostic markers and infiltrating immune cells was analyzed.
Herein, we identified 46 DEGs, and enrichment analysis results showed that DEGs and several kinds of signaling pathways might be closely associated with the occurrence and progression of NPC. DTL was recognized as NPC-related biomarker. DTL, also known as retinoic acid-regulated nuclear matrix-associated protein (RAMP), or DNA replication factor 2 (CDT2), is reported to be correlated with the cell proliferation, cell cycle arrest and cell invasion in hepatocellular carcinoma, breast cancer and gastric cancer. Immune infiltration analysis demonstrated that macrophages M0, macrophages M1 and T cells CD4 memory activated were linked to pathogenesis of NPC.
In summary, we adopted a comprehensive strategy to screen DTL as biomarkers related to NPC and explore the critical role of immune cell infiltration in NPC.
尽管鼻咽癌（NPC）的基础和临床研究已取得显著进展，但NPC进展的生物标志物尚未得到充分研究和描述。本研究旨在通过综合分析确定NPC潜在的新型生物标志物，并探讨这一病理过程中的免疫细胞浸润情况。
从基因表达综合数据库（GEO）下载五个GEO数据集并进行分析，以鉴定差异表达基因（DEG），随后进行基因本体（GO）和京都基因与基因组百科全书（KEGG）富集分析。采用四种算法筛选NPC的新型关键生物标志物，包括随机森林（RF）机器学习算法、最小绝对收缩和选择算子（LASSO）逻辑回归、支持向量机递归特征消除（SVM-RFE）和加权基因共表达网络分析（WGCNA）。最后，使用CIBERSORT评估NPC中免疫细胞的浸润情况，并分析诊断标志物与浸润免疫细胞之间的相关性。
在此，我们鉴定出46个DEG，富集分析结果表明DEG和几种信号通路可能与NPC的发生和进展密切相关。DTL被识别为与NPC相关的生物标志物。DTL，也称为视黄酸调节的核基质相关蛋白（RAMP）或DNA复制因子2（CDT2），据报道与肝细胞癌、乳腺癌和胃癌中的细胞增殖、细胞周期停滞和细胞侵袭相关。免疫浸润分析表明，M0巨噬细胞、M1巨噬细胞和CD4记忆激活T细胞与NPC的发病机制有关。
总之，我们采用综合策略筛选出DTL作为与NPC相关的生物标志物，并探讨了免疫细胞浸润在NPC中的关键作用。
