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粒细胞集落刺激因子作为肝细胞癌总生存期的潜在分子靶点。

GCSF as a Potential Molecular Target for Overall Survival of Hepatocellular Carcinoma.

作者信息

Cao Heng, Guo Peng, Wu Xiaohui, Li Jiankun, Ge Chenlong, Wang Shunxiang

机构信息

Department of Hepatobiliary Surgery, The Fourth Hospital of Hebei Medical University, 12 Health Road, Shijiazhuang, Hebei 050011, P.R. China.

Department of Orthopedics, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, P.R. China.

出版信息

Comb Chem High Throughput Screen. 2022;25(6):1005-1023. doi: 10.2174/1386207324666210322124003.

Abstract

BACKGROUND

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors of the digestive tract in the world. Therefore, it is important to carry out studies on the molecular mechanisms of early diagnosis and treatment of HCC to reduce mortality.

METHODS

Bioinformatic analysis was performed to explore the significant role of GCSF on the occurrence and development of neoplasm. Differently expressed genes (DEGs) were screened, and the significant hub genes related to GCSF were identified by the multiple algorithms of Cytoscape. Functional annotation for DEGs, pathological stage, and overall survival analysis were implemented. In addition, the verification for the role of GCSF on HCC was made via the clinical samples. A total of 70 participates diagnosed as HCC were recruited from November 2014 to November 2019. The immunohistochemistry assay, qRT-PCR, receiver operating characteristic (ROC) curves, and overall survival analysis were carried out.

RESULTS

GCSF was related to the tumor size, and the expression of GCSF was up-regulated in hepatocellular carcinoma tissues. The enrichment results of GO and KEGG analysis were mainly enriched in "Inflammatory response", "Protein binding", "Metabolic pathways", and "Proteasome". The tumor diameter (P < 0.001), and survival time (P < 0.001) were significantly associated with the expression of GCSF via the verification of clinical data. The univariate and multivariate Cox proportional regression analysis manifested that high expression of GCSF in patients with HCC was related to poor OS.

CONCLUSION

The expression level of GCSF is significantly associated with the prognostic survival of HCC, and it is expected to become a new prognostic marker of HCC, providing a novel idea for future basic research as well as targeted therapy.

摘要

背景

肝细胞癌(HCC)是世界上最常见的消化道恶性肿瘤之一。因此,开展HCC早期诊断和治疗的分子机制研究以降低死亡率具有重要意义。

方法

进行生物信息学分析以探讨GCSF在肿瘤发生发展中的重要作用。筛选差异表达基因(DEGs),并通过Cytoscape的多种算法鉴定与GCSF相关的重要枢纽基因。对DEGs进行功能注释、病理分期和总生存分析。此外,通过临床样本验证GCSF对HCC的作用。2014年11月至2019年11月共招募了70例诊断为HCC的参与者。进行免疫组织化学检测、qRT-PCR、受试者工作特征(ROC)曲线分析和总生存分析。

结果

GCSF与肿瘤大小相关,且GCSF在肝细胞癌组织中的表达上调。GO和KEGG分析的富集结果主要集中在“炎症反应”、“蛋白质结合”、“代谢途径”和“蛋白酶体”。通过临床数据验证,肿瘤直径(P < 0.001)和生存时间(P < 0.001)与GCSF的表达显著相关。单因素和多因素Cox比例回归分析表明,HCC患者中GCSF的高表达与较差的总生存期相关。

结论

GCSF的表达水平与HCC的预后生存显著相关,有望成为HCC新的预后标志物,为未来的基础研究和靶向治疗提供新思路。

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