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IF 6.2 Q1 IMMUNOLOGY

ImmunoTargets and Therapy Pub Date : 2025-02-28 eCollection Date: 2025-01-01 DOI:10.2147/ITT.S497284

Kai Nan, Lei Zhang, Yujia Zou, Zilong Geng, Jing Huang, Yulong Peng, Su Yin, Ming Zhang

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引用次数: 0

摘要

目的：Kinesin家族成员18A （KIF18A）是运动蛋白Kinesin -8家族成员，参与多种肿瘤的进展和转移。然而，其在胰腺腺癌（PAAD）中的作用尚不清楚。方法：为了评估这一作用，从癌症基因组图谱（TCGA）和基因表达综合数据库（GEO）中获得了RNA测序数据集，并补充了相关的临床元数据。KIF18A在PAAD中的蛋白表达水平来源于human protein atlas （HPA）数据库。通过多变量Cox回归和Lasso回归分析，确定KIF18A表达水平和预后相关基因的差异，构建预后风险模型。在免疫治疗组和KIF18A表达组中，评估KIF18A高表达组和低表达组的肿瘤突变负荷（Tumor Mutation Burden， TMB）、微卫星（Microsatellite， MSI）、免疫景观、突变景观和药物敏感性。最后，通过体外实验阐明KIF18A在调控PAAD恶性行为中的分子功能。结果：KIF18A在PAAD中高表达，与临床分期差、预后差密切相关。单细胞分析显示KIF18A主要表达于肿瘤细胞的微管中，参与了PAAD的有丝分裂和细胞周期。进一步分析发现KIF18A的表达与TMB、MSI和免疫细胞浸润密切相关。体外实验证实KIF18A促进PAAD粘附分子的增殖、迁移和表达，抑制血管生成。此外，KIF18A的高表达与铁下垂和m6A基因表达呈正相关，其高表达是由KRAS和TP53突变驱动的。结论：本研究证实KIF18A可作为预测PAAD预后和免疫治疗的标志物，参与PAAD细胞微管的形成，促进PAAD的恶性行为。

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Integrated Profiling Delineated KIF18A as a Significant Biomarker Associated with Both Prognostic Outcomes and Immune Response in Pancreatic Cancer.

Purpose: Kinesin family member 18A (KIF18A) is a member of the kinesin-8 family of motor proteins, involved in the progression and metastasis of various tumors. However, its role in pancreatic adenocarcinoma (PAAD) remains unclear.

Methods: To evaluate that role, RNA sequencing datasets, complemented by pertinent clinical metadata, were procured from the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) repositories. The protein expression level of KIF18A in PAAD was derived from human protein atlas (HPA) database. The differences in KIF18A expression levels and prognostic related genes were identified through multivariate Cox regression and Lasso regression analysis to construct a prognostic risk model. The Tumor Mutation Burden (TMB), Microsatellite (MSI), immune landscape, mutation landscape and drug sensitivity of high- and low-expression KIF18A groups were assessed in immunotherapy cohorts and KIF18A expression cohorts. Finally, in vitro experiments were conducted to elucidate the molecular function of KIF18A in regulating the malignant behavior of PAAD.

Results: KIF18A is highly expressed in PAAD and is closely related to worse clinical stage and poor prognosis. Single cell analysis revealed that KIF18A is mainly expressed in microtubules of tumor cells and participated in mitosis and cell cycle of PAAD. Further analysis revealed that the expression of KIF18A is closely related to TMB, MSI, and immune cell infiltration. In vitro experiments confirmed that KIF18A promotes the proliferation, migration and expression of adhesion molecules in PAAD, and inhibits angiogenesis. In addition, the high expression of KIF18A is positively related to ferroptosis and m6A genes expression, and its high expression is driven by mutated KRAS and TP53.

Conclusion: This study confirmed that KIF18A can be used as a marker to predict the prognosis and immunotherapy of PAAD, and it participates in the formation of microtubules in PAAD cells and promotes the malignant behavior of PAAD.

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来源期刊

ImmunoTargets and Therapy IMMUNOLOGY-

CiteScore

16.50

自引率

0.00%

发文量

审稿时长

16 weeks

期刊介绍： Immuno Targets and Therapy is an international, peer-reviewed open access journal focusing on the immunological basis of diseases, potential targets for immune based therapy and treatment protocols employed to improve patient management. Basic immunology and physiology of the immune system in health, and disease will be also covered.In addition, the journal will focus on the impact of management programs and new therapeutic agents and protocols on patient perspectives such as quality of life, adherence and satisfaction.