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整合多组学数据分析揭示了TXNIP在三阴性乳腺癌中的临床意义及其对免疫微环境的作用。

Integrated multiomic data analysis reveals the clinical significance of TXNIP and contributing to immune microenvironment in triple negative breast cancer.

作者信息

Gong Han, Zhang PeiHe, Hu Xingming, Zhang Bin

机构信息

The 1st Department of Thoracic Surgery of Hunan Cancer Hospital & the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 4100013, China; Molecular Biology Research Center and Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China.

Department of Histology and Embryology, Xiangya School of Medicine, Central South University, Changsha, China.

出版信息

Transl Oncol. 2024 Jan;39:101808. doi: 10.1016/j.tranon.2023.101808. Epub 2023 Oct 26.

Abstract

Triple negative breast cancer (TNBC) is a type of breast cancer with the worst clinical outcome. TNBC is not sensitive to typical endocrine therapy and targeted therapy. Thioredoxin interacting protein (TXNIP), known as a tumor suppressor, is related to oxidative stress and energy metabolism. However, the clinical significance of TXNIP in TNBC and mechanism in immunity have not been fully reported. In this study, we found that the expression of TXNIP was downregulated obviously in TNBC tissues and negatively correlated with tumor grade by comprehensive bioinformatics analysis and immunohistochemistry staining of 108 TNBC tissues. Through in vivo and in vitro experiments, we identified TXNIP as a tumor suppressor in TNBC. By bulk mRNA and scRNA analysis, we found that TXNIP could enhance immune response in TNBC and was a potential biomarker for cancer immunity and immunotherapy. We also performed the drug susceptibility analysis to reveal the therapeutic value of TXNIP. In conclusion, our findings demonstrated that TXNIP was a tumor suppressor in TNBC and was involved in tumor malignancy progression. TXNIP was a potential biomarker for immunotherapy and promising molecular therapeutic target.

摘要

三阴性乳腺癌(TNBC)是一种临床预后最差的乳腺癌类型。TNBC对典型的内分泌治疗和靶向治疗不敏感。硫氧还蛋白相互作用蛋白(TXNIP)作为一种肿瘤抑制因子,与氧化应激和能量代谢有关。然而,TXNIP在TNBC中的临床意义及其免疫机制尚未完全报道。在本研究中,通过对108例TNBC组织进行综合生物信息学分析和免疫组化染色,我们发现TNBC组织中TXNIP的表达明显下调,且与肿瘤分级呈负相关。通过体内和体外实验,我们确定TXNIP是TNBC中的一种肿瘤抑制因子。通过批量mRNA和单细胞RNA分析,我们发现TXNIP可以增强TNBC中的免疫反应,是癌症免疫和免疫治疗的潜在生物标志物。我们还进行了药物敏感性分析,以揭示TXNIP的治疗价值。总之,我们的研究结果表明TXNIP是TNBC中的一种肿瘤抑制因子,参与肿瘤恶性进展。TXNIP是免疫治疗的潜在生物标志物和有前景的分子治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/16fb/10630669/9a1c8cced75e/gr1.jpg

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