背景:大多数肿瘤组织表达纺锤体极体成分25(SPC25),NDC80复合物的四个亚基之一,与周围的正常组织相比,水平更高。根据早期的研究,这个亚基强烈促进肿瘤细胞增殖和肿瘤生长,导致肝细胞患者预后较差,乳房,肺,和前列腺癌。正是因为SPC25在子宫内膜癌(UCEC)中的作用研究不足,我们选择专注于UCEC,以获得对SPC25的更科学和透彻的理解。
方法:除了检查SPC25的差异表达,预后意义,和UCEC中的生物学功能,我们的研究试图从甲基化和免疫浸润的角度阐明SPC25影响UCEC病程和患者预后的潜在机制.
结果:我们观察到SPC25基因在UCEC不同临床病理特征中的差异表达,并确定SPC25是总生存期(OS)较差的危险因素。疾病特异性生存率(DSS),和UCEC中的无进展间隔(PFI),特别是在其多种临床亚型中。此外,我们还发现SPC25及其共表达的基因主要参与与UCEC中细胞周期和细胞分裂相关的生物过程和信号转导途径。在调查SPC25的甲基化状态后,我们发现,由于SPC25基因序列中CpG位点的低甲基化,UCEC患者SPC25表达升高,预后不良.最后,我们研究了SPC25在免疫治疗中的潜在作用,发现SPC25可能通过调节免疫调节分子和趋化因子的表达来改变肿瘤微环境(TME)中主要免疫细胞的浸润水平,这将有利于SPC25控制UCEC的进展。
结论:结论:SPC25是有用的预测性生物标志物以及UCEC的可能治疗靶标。
BACKGROUND: Most tumor tissues expressed spindle pole body component 25 (SPC25), one of the four subunits of the NDC80 complex, at greater levels compared to surrounding normal tissues. According to earlier researches, this subunit strongly encouraged tumor cell proliferation and tumor growth, which resulted in worse prognoses in patients with hepatocellular, breast, lung, and prostate cancer. Precisely because SPC25\'s role in uterine corpus endometrial carcinoma (UCEC) is understudied, we chose to concentrate on UCEC for gaining a more scientific and thorough understanding of SPC25.
METHODS: Along with examining SPC25\'s differential expression, prognostic significance, and biological function in UCEC, our research sought to clarify the underlying mechanism by which SPC25 influences the course of UCEC and patient prognosis from the viewpoints of methylation and immune infiltration.
RESULTS: We observed differential expression of SPC25 gene in different clinicopathological features of UCEC and identified SPC25 as a hazard factor for poorer overall survival (OS), disease-specific survival (DSS), and progress free interval (PFI) in UCEC, particularly in its multiple clinical subtypes. In addition, we also discovered that SPC25 and its co-expressed genes mostly engaged in biological processes and signal transduction routes linked to cell cycle and cell division in UCEC. After investigating SPC25\'s methylation status, we discovered that patients with UCEC had elevated SPC25 expression and a poor prognosis due to hypomethylation of CpG sites in the SPC25 gene sequence. Finally, we investigated SPC25\'s potential role in immunotherapy and discovered that SPC25 might alter the major immune cell infiltration levels in the tumor microenvironment (TME) by regulating the expression of immunoregulatory molecules and chemokines, which would be beneficial for SPC25 to control the progression of UCEC.
CONCLUSIONS: In conclusion, SPC25 was a useful predictive biomarker as well as a possible therapeutic target for UCEC.