Zhou Chang-Shuai, Feng Ming-Tao, Chen Xin, Gao Yang, Chen Lei, Li Liang-Dong, Li De-Heng, Cao Yi-Qun
Department of Neurosurgery, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.
Onco Targets Ther. 2021 Feb 15;14:1033-1048. doi: 10.2147/OTT.S286274. eCollection 2021.
Exonuclease 1 (EXO1) has been identified to be highly expressed in different human malignancies, but its expression and prognostic role in lung adenocarcinoma (LUAD) remain unknown.
Two independent cohorts extracted from public databases and one cohort from our center were analyzed in this study. Expression levels of EXO1 in LUAD tissues and paired para-cancer tissues were detected. The prognostic value of EXO1 in LUAD patients was evaluated in the three cohorts. Enrichment analyses were performed to explore the possible underlying biological pathways. Moreover, we also explored the correlations between EXO1 and tumor-infiltrating immune cells and evaluated the impact of EXO1 knock-down on the migration of lung cancer cells.
In this study, we found that EXO1 was highly expressed in LUAD tissues compared with para-cancerous tissues in public databases ( < 0.01), which was consistent with our data ( < 0.01). Survival analysis indicated that high expression of EXO1 was associated with poor prognosis in LUAD ( < 0.01). Enrichment analyses indicated that biological pathways like cell cycle regulation, DNA damage and repair, immune response, neuroactive ligand-receptor interaction, may be associated with EXO1 aberrant expression. Moreover, high expression of EXO1 was correlated with decreased infiltrating B cells ( < 0.01) and CD4+ T cells ( < 0.01) levels, and low infiltrating levels of B cells ( < 0.01) and dendritic cells (DCs) ( < 0.05) indicated poor overall survival (OS) in LUAD. Additionally, in vitro experiments suggested that knockdown of EXO1 may inhibit the migratory ability of lung cancer cells.
In conclusion, EXO1 is a potential prognostic biomarker in LUAD, and correlates with infiltrating levels of immune cells in the tumor microenvironment. Further prospective validation of EXO1 in lung cancer is warranted.
已确定核酸外切酶1（EXO1）在不同人类恶性肿瘤中高表达，但其在肺腺癌（LUAD）中的表达及预后作用尚不清楚。
本研究分析了从公共数据库提取的两个独立队列以及来自我们中心的一个队列。检测了LUAD组织和配对癌旁组织中EXO1的表达水平。在这三个队列中评估了EXO1在LUAD患者中的预后价值。进行富集分析以探索可能的潜在生物学途径。此外，我们还探讨了EXO1与肿瘤浸润免疫细胞之间的相关性，并评估了EXO1敲低对肺癌细胞迁移的影响。
在本研究中，我们发现与公共数据库中的癌旁组织相比，LUAD组织中EXO1高表达（<0.01），这与我们的数据一致（<0.01）。生存分析表明，EXO1高表达与LUAD患者预后不良相关（<0.01）。富集分析表明，细胞周期调控、DNA损伤与修复、免疫反应、神经活性配体-受体相互作用等生物学途径可能与EXO1异常表达有关。此外，EXO1高表达与浸润性B细胞（<0.01）和CD4+T细胞（<0.01）水平降低相关，而B细胞（<0.01）和树突状细胞（DCs）（<0.05）浸润水平低表明LUAD患者总生存期（OS）较差。此外，体外实验表明，敲低EXO1可能抑制肺癌细胞的迁移能力。
总之，EXO1是LUAD中一种潜在的预后生物标志物，与肿瘤微环境中免疫细胞的浸润水平相关。有必要对EXO1在肺癌中的作用进行进一步的前瞻性验证。
