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SPIN1在胃癌中的基因表达谱分析:对肿瘤发生及潜在治疗靶点的见解

Gene expression profiling of SPIN1 in gastric cancer: insights into tumorigenesis and potential therapeutic targets.

作者信息

Lv Bei-Bei, Cai Lei, Xiao Yao, Wang Rui-Han, Lin Xiao-Yan

机构信息

Department of Pathology, Shandong Provincial Hospital Affiliated To Shandong First Medical University, Jinan, Shandong, China.

出版信息

Front Genet. 2025 Jun 11;16:1510849. doi: 10.3389/fgene.2025.1510849. eCollection 2025.

Abstract

BACKGROUND

Gastric cancer (GC) is a prevalent malignant tumor globally, posing a significant threat to human health. The histone code reader Spindlin1 (SPIN1) has been implicated in tumorigenesis and tumor progression, however, the exact molecular mechanisms underlying these processes remain incompletely understood. The biological function and regulatory mechanisms of SPIN1 in GC remain ambiguous. This study aims to investigate the regulatory mechanisms of SPIN1 in the pathogenesis and progression of GC, as well as to identify genes closely associated with SPIN1 and potential biomarkers.

METHODS

Gene expression profiles from 375 patients diagnosed with gastric cancer (GC) and 32 control subjects were obtained from the TCGA-STAD database. Our study examined the relationships between SPIN1 expression and various factors including tumor progression, clinical stage, survival status, immune microenvironment and drug sensitivity within the cohort of 375 GC patients and 32 controls. Furthermore, we investigated the interplay between m6A and 5 mC regulators in influencing the expression of SPIN1 in GC, and identified genes with significant correlations with SPIN1 through Spearman correlation analysis.

RESULTS

A significantly elevated expression of SPIN1 was found in 375 GC patients compared to 32 control subjects. SPIN1 expression was positively correlated with EMT score and angiogenesis score. Cell proliferation-related gene sets (myogenesis, mitotic spindle and G2M checkpoint) were all significantly associated with the high SPIN1 GC group. Eosinophils was associated with high expression of SPIN1. A total of 21 checkpoints were associated with SPIN1 expression. Low SPIN1 expression group could benefit from Axitinib, Cytarabine, Pazopanib and Sunitinib. Most m6A regulators and a subset of m5C regulators were positively associated with SPIN1. Finally, we screened the 10 genes with the strongest correlation with SPIN1, among which CDH11 and SLC8A1 were associated with the prognosis of GC.

CONCLUSION

In conclusion, our study has provided valuable insights into the pivotal role of SPIN1 in GC development, elucidating its potential molecular mechanisms and establishing it as a promising therapeutic target.

摘要

背景

胃癌(GC)是全球普遍存在的恶性肿瘤,对人类健康构成重大威胁。组蛋白编码阅读器Spindlin1(SPIN1)与肿瘤发生和肿瘤进展有关,然而,这些过程背后的确切分子机制仍未完全了解。SPIN1在胃癌中的生物学功能和调控机制仍不明确。本研究旨在探讨SPIN1在胃癌发病机制和进展中的调控机制,并确定与SPIN1密切相关的基因和潜在的生物标志物。

方法

从TCGA-STAD数据库中获取375例胃癌(GC)患者和32例对照受试者的基因表达谱。我们的研究在375例GC患者和32例对照的队列中,研究了SPIN1表达与肿瘤进展、临床分期、生存状态、免疫微环境和药物敏感性等各种因素之间的关系。此外,我们研究了m6A和5mC调节剂在影响GC中SPIN1表达方面的相互作用,并通过Spearman相关分析确定了与SPIN1具有显著相关性的基因。

结果

与32例对照受试者相比,375例GC患者中SPIN1表达显著升高。SPIN1表达与EMT评分和血管生成评分呈正相关。细胞增殖相关基因集(肌发生、有丝分裂纺锤体和G2M检查点)均与高SPIN1 GC组显著相关。嗜酸性粒细胞与SPIN1高表达相关。共有21个检查点与SPIN1表达相关。低SPIN1表达组可从阿昔替尼、阿糖胞苷、帕唑帕尼和舒尼替尼中获益。大多数m6A调节剂和一部分m5C调节剂与SPIN1呈正相关。最后,我们筛选出与SPIN1相关性最强的10个基因,其中CDH11和SLC8A1与GC的预后相关。

结论

总之,我们的研究为SPIN1在胃癌发生中的关键作用提供了有价值的见解,阐明了其潜在的分子机制,并将其确立为一个有前景的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a27/12188309/427fdf8b158c/fgene-16-1510849-g001.jpg

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