背景:SEPT9是一种关键的细胞骨架GTP酶,可调节包括有丝分裂和胞质分裂在内的多种生物学过程。虽然先前的研究涉及SEPT9与肿瘤发生和发展有关,但尚未进行全面的泛癌症分析。本研究旨在系统探讨其在癌症筛查中的作用,预后,和治疗,解决这一关键差距。
方法:包含临床信息的基因和蛋白质表达数据从公共数据库获得,用于泛癌症分析。此外,我们使用来自90例肺鳞癌(LUSC)患者的临床样本,进一步通过实验验证SEPT9的临床意义.此外,分子对接工具用于分析SEPT9蛋白与药物之间的亲和力.
结果:SEPT9在各种癌症中高表达,其异常表达与遗传变化和表观遗传修饰相关,导致不良临床结果。以LUSC为例,额外的数据集分析和免疫组织化学实验进一步证实了SEPT9基因和蛋白的诊断和预后价值以及临床相关性.功能富集,单细胞表达,和免疫浸润分析显示,SEPT9促进恶性肿瘤进展和调节免疫微环境,使患者受益于免疫疗法。此外,药物敏感性和分子对接分析表明,SEPT9与多种药物的敏感性和耐药性有关,包括Vorinostat和OTS-964。为了利用其在LUSC中的预后和治疗潜力,有丝分裂纺锤体相关预后模型,包括SEPT9、HSF1、ARAP3、KIF20B、FAM83D,TUBB8和几个临床特征,已开发。该模型不仅改善了临床结果预测,而且重塑了免疫微环境,使免疫疗法对LUSC患者更有效。
结论:这是第一个系统分析SEPT9在癌症中的作用并创新性地将有丝分裂纺锤体相关模型应用于LUSC的研究,充分展示其作为癌症筛查和预后的有价值的生物标志物的潜力,并突出其在促进免疫治疗和化疗中的应用价值,特别是对于LUSC。
BACKGROUND: SEPT9 is a pivotal cytoskeletal GTPase that regulates diverse biological processes encompassing mitosis and cytokinesis. While previous studies have implicated SEPT9 in tumorigenesis and development; comprehensive pan-cancer analyses have not been performed. This study aims to systematically explore its role in cancer screening, prognosis, and treatment, addressing this critical gap.
METHODS: Gene and protein expression data containing clinical information were obtained from public databases for pan-cancer analyses. Additionally, clinical samples from 90 patients with lung squamous cell carcinoma (LUSC) were used to further experimentally validate the clinical significance of SEPT9. In addition, the molecular docking tool was used to analyze the affinities between SEPT9 protein and drugs.
RESULTS: SEPT9 is highly expressed in various cancers, and its aberrant expression correlates with genetic alternations and epigenetic modifications, leading to adverse clinical outcomes. Take LUSC as an example, additional dataset analyses and immunohistochemical experiments further confirm the diagnostic and prognostic values as well as the clinical relevance of the SEPT9 gene and protein. Functional enrichment, single-cell expression, and immune infiltration analyses revealed that SEPT9 promotes malignant tumor progression and modulates the immune microenvironments, enabling patients to benefit from immunotherapy. Moreover, drug sensitivity and molecular docking analyses showed that SEPT9 is associated with the sensitivity and resistance of multiple drugs and has stable binding activity with them, including Vorinostat and OTS-964. To harness its prognostic and therapeutic potential in LUSC, a mitotic spindle-associated prognostic model including SEPT9, HSF1, ARAP3, KIF20B, FAM83D, TUBB8, and several clinical characteristics, was developed. This model not only improves clinical outcome predictions but also reshapes the immune microenvironment, making immunotherapy more effective for LUSC patients.
CONCLUSIONS: This is the first study to systematically analyze the role of SEPT9 in cancers and innovatively apply the mitotic spindle-associated model to LUSC, fully demonstrating its potential as a valuable biomarker for cancer screening and prognosis, and highlighting its application value in promoting immunotherapy and chemotherapy, particularly for LUSC.