Li Bo, Gu Xiaojuan, Zhang Hanbing, Xiong Hao
Department of Respiratory and Critical Care Medicine, The Second People's Hospital of Yibin, Yibin City, People's Republic of China.
Anim Cells Syst (Seoul). 2022 May 24;26(3):108-118. doi: 10.1080/19768354.2022.2079718. eCollection 2022.
High expression levels of the TTK gene are closely related to tumor occurrence and poor prognosis, as confirmed by some studies. Our study explored the prognosis of lung adenocarcinoma (LUAD) patients with different TTK levels and the possible pathological mechanism of TTK in LUAD.
We extensively searched literature databases and high-throughput sequencing databases and included relevant literature or datasets in the meta-analysis according to the inclusion and exclusion criteria. Hazard ratios (HRs) and 95% confidence intervals (CIs) related to TTK expression were calculated, publication bias was assessed, and sensitivity tests were performed. We also compared the relationship between cancer immune infiltrating cells and tumor mutation burden (TMB) in patients with different TTK expression levels via bioinformatics analysis. The half maximal inhibitory concentration (IC50) of some chemotherapeutic and targeted therapy drugs were calculated. The potential biological functions or pathways associated with different TTK expression levels were determined by gene set enrichment analysis (GSEA).
The meta-analysis revealed that higher TTK expression level was significantly associated with poor prognosis in LUAD patients, both in overall survival (OS) and progression-free survival (PFS). The expression level of TTK was significantly correlated with presence of some immune cells and TMB. Tumors with higher TTK expression levels were mostly enriched for the cell cycle, DNA replication and homologous recombination pathways. In addition, patients with different TTK expression levels were differently sensitive to some antitumor drugs.
TTK may be a promising prognostic biomarker for LUAD and is worthy of further investigation.
一些研究证实,TTK基因的高表达水平与肿瘤发生及不良预后密切相关。我们的研究探讨了不同TTK水平的肺腺癌(LUAD)患者的预后情况以及TTK在LUAD中的可能病理机制。
我们广泛检索了文献数据库和高通量测序数据库,并根据纳入和排除标准将相关文献或数据集纳入荟萃分析。计算与TTK表达相关的风险比(HRs)和95%置信区间(CIs),评估发表偏倚,并进行敏感性检验。我们还通过生物信息学分析比较了不同TTK表达水平患者的癌症免疫浸润细胞与肿瘤突变负荷(TMB)之间的关系。计算了一些化疗和靶向治疗药物的半数最大抑制浓度(IC50)。通过基因集富集分析(GSEA)确定与不同TTK表达水平相关的潜在生物学功能或途径。
荟萃分析显示,在总生存期(OS)和无进展生存期(PFS)方面,较高的TTK表达水平与LUAD患者的不良预后显著相关。TTK的表达水平与一些免疫细胞的存在及TMB显著相关。TTK表达水平较高的肿瘤大多富集于细胞周期、DNA复制和同源重组途径。此外,不同TTK表达水平的患者对一些抗肿瘤药物的敏感性不同。
TTK可能是LUAD一个有前景的预后生物标志物,值得进一步研究。