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通过mRNA转录谱和实验验证鉴定HOXC基因家族作为乳腺癌的预后和免疫相关生物标志物

Identification of HOXC Gene Family as Prognostic and Immune-Related Biomarkers in Breast Cancer Through mRNA Transcriptional Profile and Experimental Validation.

作者信息

Cheng Xiongtao, Luo Jie, Cao Jianxiong

机构信息

Graduate School, Hunan University of Chinese Medicine, Changsha, Hunan, China.

Department of Traditional Chinese Medicine, Yunnan University of Traditional Chinese Medicine, Kunming, Yunnan, China.

出版信息

Biochem Genet. 2024 Jul 12. doi: 10.1007/s10528-024-10884-5.

DOI:10.1007/s10528-024-10884-5
PMID:38995528
Abstract

Breast cancer (BC) is the most common malignancy in women worldwide, and more effective biomarkers are urgently needed for the prevention and treatment of BC. Our study aimed to investigate the role of the HOXC gene family (HOXCs) and its relationship with the immune response in BC. The differential expression of HOXCs and its clinical prognostic significance in BC were explored using bioinformatics analysis, and the cBioPortal database was used to evaluate the genetic mutation profile of the HOXCs in BC. The results indicated that the expression levels of HOXC4, 10, 11, 12, and 13 were significantly increased in BC tissues compared with the normal tissues, and expressions of these genes were closely associated with BC stage, among them, high expression levels of HOXC10 and HOXC13 predicted poor outcome in BC patients. In addition, to elucidate the essential role of HOXCs in the tumor microenvironment and immunotherapeutic response of BC, the impact of HOXCs on the regulation of immune infiltration in BC was comprehensively assessed. The result showed that HOXC10 and HOXC13 expressions were significantly positively linked with the infiltration levels of CD8+T cell and M1 macrophage, while they were negatively related to Mast and Natural killer cells, suggesting the important influence of HOXCs on regulating tumor immunity in BC patients. Lastly, the RT-qPCR assay was employed to validate HOXCs expression in samples of BC patients. In conclusion, HOXCs may be a promising prognostic indicator and could regulate the immune infiltration in BC patients, thus being a promising targeted immunotherapy for BC.

摘要

乳腺癌(BC)是全球女性中最常见的恶性肿瘤,迫切需要更有效的生物标志物用于BC的预防和治疗。我们的研究旨在探讨HOXC基因家族(HOXCs)的作用及其与BC免疫反应的关系。使用生物信息学分析探索HOXCs在BC中的差异表达及其临床预后意义,并使用cBioPortal数据库评估HOXCs在BC中的基因突变谱。结果表明,与正常组织相比,BC组织中HOXC4、10、11、12和13的表达水平显著升高,这些基因的表达与BC分期密切相关,其中,HOXC10和HOXC13的高表达预示着BC患者预后不良。此外,为了阐明HOXCs在BC肿瘤微环境和免疫治疗反应中的重要作用,全面评估了HOXCs对BC免疫浸润调节的影响。结果显示,HOXC10和HOXC13的表达与CD8+T细胞和M1巨噬细胞的浸润水平显著正相关,而与肥大细胞和自然杀伤细胞呈负相关,提示HOXCs对调节BC患者肿瘤免疫具有重要影响。最后,采用RT-qPCR检测验证BC患者样本中HOXCs的表达。总之,HOXCs可能是一个有前景的预后指标,并且可以调节BC患者的免疫浸润,因此是一种有前景的BC靶向免疫疗法。

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本文引用的文献

1
Mast cells in colorectal cancer tumour progression, angiogenesis, and lymphangiogenesis.结直肠癌肿瘤进展、血管生成和淋巴管生成中的肥大细胞。
Front Immunol. 2023 Jul 11;14:1209056. doi: 10.3389/fimmu.2023.1209056. eCollection 2023.
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Emerging role of interactions between tumor angiogenesis and cancer stem cells.肿瘤血管生成与癌症干细胞相互作用的新作用。
J Control Release. 2023 Aug;360:468-481. doi: 10.1016/j.jconrel.2023.06.036. Epub 2023 Jul 12.
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Frenemies in the Microenvironment: Harnessing Mast Cells for Cancer Immunotherapy.
微环境中的“亦敌亦友”:利用肥大细胞进行癌症免疫治疗
Pharmaceutics. 2023 Jun 9;15(6):1692. doi: 10.3390/pharmaceutics15061692.
4
Potential prognostic and immunotherapeutic value of calponin 1: A pan-cancer analysis.钙调蛋白1的潜在预后及免疫治疗价值:一项泛癌分析
Front Pharmacol. 2023 Apr 21;14:1184250. doi: 10.3389/fphar.2023.1184250. eCollection 2023.
5
The Great Immune Escape: Understanding the Divergent Immune Response in Breast Cancer Subtypes.免疫大逃脱:理解乳腺癌亚型中的不同免疫反应。
Cancer Discov. 2023 Jan 9;13(1):23-40. doi: 10.1158/2159-8290.CD-22-0475.
6
Prognostic and Immunological Role of across Cancers: Friend or Foe?在多种癌症中的预后和免疫作用:是敌是友?
Int J Mol Sci. 2022 Sep 30;23(19):11590. doi: 10.3390/ijms231911590.
7
HOXC10 Promotes Metastasis in Colorectal Cancer by Recruiting Myeloid-derived Suppressor Cells.HOXC10通过募集髓源性抑制细胞促进结直肠癌转移。
J Cancer. 2022 Sep 6;13(12):3308-3317. doi: 10.7150/jca.76945. eCollection 2022.
8
Gene expression signatures of individual ductal carcinoma in situ lesions identify processes and biomarkers associated with progression towards invasive ductal carcinoma.个体导管原位癌病变的基因表达特征可识别与向浸润性导管癌进展相关的过程和生物标志物。
Nat Commun. 2022 Jun 13;13(1):3399. doi: 10.1038/s41467-022-30573-4.
9
Current and future diagnostic and treatment strategies for patients with invasive lobular breast cancer.浸润性小叶乳腺癌患者的当前和未来诊断及治疗策略。
Ann Oncol. 2022 Aug;33(8):769-785. doi: 10.1016/j.annonc.2022.05.006. Epub 2022 May 21.
10
The expression of is correlated with tumor-infiltrating immune cells in basal-like breast cancer and serves as a prognostic biomarker.[具体物质]的表达与基底样乳腺癌中的肿瘤浸润免疫细胞相关,并作为一种预后生物标志物。 (注:原文中“of”后面缺少具体内容)
Ann Transl Med. 2022 Jan;10(2):81. doi: 10.21037/atm-21-6611.