Table_2_KNL1 is a prognostic and diagnostic biomarker related to immune infiltration in patients with uterine corpus endometrial carcinoma.docx

BackgroundThe incidence and mortality of uterine corpus endometrial carcinoma (UCEC) are increasing yearly. There is currently no screening test for UCEC, and progress in its treatment is limited. It is important to identify new biomarkers for screening, diagnosing and predicting the outcomes of UCEC. A large number of previous studies have proven that KNL1 is crucial in the development of lung cancer, colorectal cancer and cervical cancer, but there is a lack of studies about the role of KNL1 in the development of UCEC.
MethodsThe mRNA and protein expression data of KNL1 in The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and UALCAN databases and related clinical data were used to analyze the expression differences and clinical correlations of KNL1 in UCEC. A total of 108 clinical samples were collected, and the results of bioinformatics analysis were verified by immunohistochemistry. KNL1 and its related differentially expressed genes were used to draw a volcano map, construct a PPI protein interaction network, and perform gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), gene set enrichment analysis (GSEA) and immune infiltration analysis to predict the function of KNL1 during UCEC progression. The prognostic data of TCGA and 108 clinical patients were used to analyze the correlation of KNL1 expression with the survival of patients, and KM survival curves were drawn. The UCEC cell lines Ishikawa and Hec-1-A were used to verify the function of KNL1.
ResultsKNL1 is significantly overexpressed in UCEC and is associated with a poor prognosis. KNL1 overexpression is closely related to cell mitosis, the cell cycle and other functions and is correlated with the International Federation of Gynecology and Obstetrics (FIGO) stage, histological grade and other characteristics of UCEC patients. Knockdown of KNL1 expression in UCEC cell lines can inhibit their proliferation, invasion, metastasis and other phenotypes.
ConclusionKNL1 is a prognostic and diagnostic biomarker associated with immune evasion in patients with UCEC.

背景：子宫体子宫内膜癌（uterine corpus endometrial carcinoma, UCEC）的发病率与死亡率呈逐年上升趋势。目前临床尚无针对UCEC的标准化筛查手段，且其治疗领域的进展相对有限。因此，发掘可用于UCEC筛查、诊断及预后预测的新型生物标志物具有重要的临床意义。既往多项研究证实，KNL1（KNL1）在肺癌、结直肠癌及宫颈癌的发生发展中发挥关键调控作用，但目前关于KNL1在UCEC发生发展中所发挥作用的研究仍较为匮乏。
方法：本研究获取癌症基因组图谱（The Cancer Genome Atlas, TCGA）、基因表达综合数据库（Gene Expression Omnibus, GEO）及UALCAN数据库中KNL1的mRNA与蛋白表达数据及相关临床资料，分析KNL1在UCEC组织与正常对照组织中的表达差异及其临床相关性。本研究共收集108例临床样本，通过免疫组织化学实验对生物信息学分析结果进行验证。此外，基于KNL1及其相关差异表达基因绘制火山图，构建蛋白质-蛋白质相互作用（protein-protein interaction, PPI）网络，并开展基因本体（Gene Ontology, GO）富集分析、京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes, KEGG）通路富集分析、基因集富集分析（Gene Set Enrichment Analysis, GSEA）以及免疫浸润分析，以系统预测KNL1在UCEC发生发展中的潜在生物学功能。利用TCGA数据库的患者预后数据及本研究收集的108例临床样本的随访资料，分析KNL1表达水平与患者生存情况的相关性，并绘制KM生存曲线。本研究选用UCEC细胞系Ishikawa与Hec-1-A，通过细胞功能实验验证KNL1的生物学作用。
结果：KNL1在UCEC组织中呈现显著高表达，且与患者不良预后显著相关。KNL1高表达与细胞有丝分裂、细胞周期调控等生物学过程密切相关，同时与UCEC患者的国际妇产科联盟（International Federation of Gynecology and Obstetrics, FIGO）分期、组织学分级等临床病理特征存在显著关联。在UCEC细胞系中敲低KNL1的表达水平，可显著抑制肿瘤细胞的增殖、侵袭、迁移等恶性表型。
结论：KNL1可作为UCEC患者的预后及诊断生物标志物，其调控作用与UCEC的免疫逃逸过程密切相关。