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评估H2BC9作为头颈部鳞状细胞癌潜在的诊断和预后生物标志物。

Evaluating H2BC9 as a potential diagnostic and prognostic biomarker in head and neck squamous cell carcinoma.

作者信息

Wu Lanhua, Li Liang, Zhu Mingjing, Zhou Ziyan, Su Xuejin, Jiang Yueming, Kang Min, Jiang Li

机构信息

Department of Radiation Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi, China.

Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor (Guangxi Medical University) , Ministry of Education, Nanning, 530021, Guangxi, China.

出版信息

Eur J Med Res. 2025 Jan 27;30(1):54. doi: 10.1186/s40001-025-02301-3.

Abstract

BACKGROUND

Histone H2B is highly expressed in many types of cancers and is involved in cancer development. H2B clustered histone 9 (H2BC9), a member of the H2B family, plays critical roles in gene expression regulation, chromosome structure, DNA repair stability, and cell cycle regulation. However, the diagnostic and prognostic value of H2BC9 in head and neck squamous cell carcinoma (HNSCC) remains unclear. This study aimed to evaluate the potential diagnostic and prognostic value of H2BC9 in HNSCC and investigate its biological role using bioinformatics.

METHODS

The expression pattern and diagnostic value of H2BC9 in HNSCC were explored using UCSC Xena and GEO database. H2BC9 expression was validated using the Human Protein Atlas database, qRT-PCR, and western blotting. Prognostic value was assessed using Kaplan-Meier curves, Cox regression analysis, and a nomogram. Drug sensitivity was predicted using the R package pRRophetic, and molecular interactions were analyzed using the DepMap database. The impact of H2BC9 on HNSCC cells was further investigated through in vitro experiments.

RESULTS

H2BC9 was markedly upregulated in HNSCC cell lines and tissues. High expression of H2BC9 was correlated with advanced-stage disease and poor prognosis. KEGG analysis linked H2BC9 to cell cycle regulation and DNA replication. H2BC9 expression influenced the drug sensitivity of paclitaxel, docetaxel, cisplatin, and 5-fluorouracil. Key molecules, such as TONSL, PITX2, NOTCH1, and H2BC10, were positively correlated with H2BC9 expression. Silencing H2BC9 suppressed cell proliferation, induced G2/M cell cycle arrest, and enhanced apoptosis and DNA damage in HNSCC cells.

CONCLUSION

We demonstrated that H2BC9 expression may be associated with HNSCC development and prognosis. These findings may provide a potential therapeutic target for HNSCC.

摘要

背景

组蛋白H2B在多种癌症中高表达,并参与癌症发展。H2B簇组蛋白9(H2BC9)是H2B家族的成员,在基因表达调控、染色体结构、DNA修复稳定性和细胞周期调控中起关键作用。然而,H2BC9在头颈部鳞状细胞癌(HNSCC)中的诊断和预后价值仍不清楚。本研究旨在评估H2BC9在HNSCC中的潜在诊断和预后价值,并使用生物信息学研究其生物学作用。

方法

使用UCSC Xena和GEO数据库探索H2BC9在HNSCC中的表达模式和诊断价值。使用人类蛋白质图谱数据库、qRT-PCR和蛋白质印迹法验证H2BC9表达。使用Kaplan-Meier曲线评估预后价值,Cox回归分析和列线图。使用R包pRRophetic预测药物敏感性,并使用DepMap数据库分析分子相互作用。通过体外实验进一步研究H2BC9对HNSCC细胞的影响。

结果

H2BC9在HNSCC细胞系和组织中明显上调。H2BC9的高表达与晚期疾病和不良预后相关。KEGG分析将H2BC9与细胞周期调控和DNA复制联系起来。H2BC9表达影响紫杉醇、多西他赛、顺铂和5-氟尿嘧啶的药物敏感性。关键分子,如TONSL、PITX2、NOTCH1和H2BC10,与H2BC9表达呈正相关。沉默H2BC9可抑制HNSCC细胞的增殖,诱导G2/M期细胞周期阻滞,并增强细胞凋亡和DNA损伤。

结论

我们证明H2BC9表达可能与HNSCC的发展和预后相关。这些发现可能为HNSCC提供潜在的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7460/11771076/2ce1347d0be4/40001_2025_2301_Fig1_HTML.jpg

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