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综合分子特征分析揭示犬尿氨酸3-单加氧酶表达与人乳腺癌肿瘤发生之间的关联

Integrated Molecular Characterization to Reveal the Association between Kynurenine 3-Monooxygenase Expression and Tumorigenesis in Human Breast Cancers.

作者信息

Tsang Yuk-Wah, Liao Chi-Hsun, Ke Chiao-Hsu, Tu Chi-Wen, Lin Chen-Si

机构信息

Department of Radiation Oncology, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chia-Yi City 600556, Taiwan.

Department of Biomedical Engineering, Chung Yuan Christian University, Taoyuan City 320314, Taiwan.

出版信息

J Pers Med. 2021 Sep 24;11(10):948. doi: 10.3390/jpm11100948.

Abstract

Kynurenine 3-monooxygenase (KMO) is overexpressed in several tumors and participates in the progression of breast cancer tumorigenesis, including cancer types such as triple-negative breast cancer (TNBC). This malignant gene is an enzyme in the kynurenine pathway, which is involved in the carcinogenesis of cancer through immune function manipulation. However, it remains unclear whether the role of the KMO contributes to tumorigenesis and immune functions in human breast cancer. In this study, we found that KMO was highly expressed in different types of tumors, especially in invasive ductal breast carcinoma. In addition, KMO expression was positively correlated with the malignant clinical features of patients with breast cancer, such as TNBC and a nodal-positive status, along with patients with a higher Nottingham prognostic index (NPI). Furthermore, the top ten KMO-correlated genes were the chemokines and pro-inflammatory cytokines known to be involved in the progression of various cancers, therefore, KMO may facilitate breast cancers via synergistically regulating inflammatory responses in tumors with these hub genes. Taken together, these findings highlight the tumor-promotion role of KMO in breast cancers and suggest that KMO can serve as a biomarker for prognosis prediction in breast cancer patients.

摘要

犬尿氨酸3-单加氧酶(KMO)在多种肿瘤中过表达,并参与乳腺癌肿瘤发生的进程,包括三阴性乳腺癌(TNBC)等癌症类型。这种恶性基因是犬尿氨酸途径中的一种酶,通过操纵免疫功能参与癌症的致癌过程。然而,KMO在人类乳腺癌的肿瘤发生和免疫功能中所起的作用仍不清楚。在本研究中,我们发现KMO在不同类型的肿瘤中高表达,尤其是在乳腺浸润性导管癌中。此外,KMO表达与乳腺癌患者的恶性临床特征呈正相关,如TNBC、淋巴结阳性状态以及诺丁汉预后指数(NPI)较高的患者。此外,与KMO相关性最高的前十位基因是已知参与各种癌症进展的趋化因子和促炎细胞因子,因此,KMO可能通过与这些枢纽基因协同调节肿瘤中的炎症反应来促进乳腺癌。综上所述,这些发现突出了KMO在乳腺癌中的促肿瘤作用,并表明KMO可作为乳腺癌患者预后预测的生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7794/8539700/f4b21edb3178/jpm-11-00948-g001.jpg

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