减数分裂核分裂1在乳腺癌中作用的综合全癌分析和实验验证。
Integrated pan-cancer analysis and experimental verification of the roles of meiotic nuclear divisions 1 in breast cancer.
发表日期:2024 Aug 23
作者:
Zhen Zhai, Zhiwei Cui, Yu Zhang, Ping Song, Jinpeng Wu, Zengqi Tan, Shuai Lin, Xiaobin Ma, Feng Guan, Huafeng Kang
来源:
Experimental Hematology & Oncology
摘要:
体细胞中减数分裂核分裂1(MND1)的异常上调被认为是肿瘤发生的驱动因素之一,但其在乳腺癌侵袭性癌(BRCA)中的表达和作用仍不清楚。因此,本研究开始对 MND1 在各种癌症中进行全面评估,并确定其在 BRCA 中的作用。基于公开数据库,包括但不限于 UCSC Xena、TCGA、GTEx、GEO、STRING、GeneMANIA 和 CancerSEA,我们评估了从泛癌角度研究MND1的表达模式、基因组特征和生物学功能,并深入探讨MND1在BRCA预后和治疗中的意义。进一步的分子生物学实验旨在确定 MND1 在 BRCA 细胞增殖、迁移和凋亡中的作用。在多种肿瘤类型中,特别是在 BRCA、COAD、HNSC、LIHC、LUAD、 LUSC、STAD 和 UCEC。 MND1 表达升高与包括 BRCA 在内的多种肿瘤的 OS 缩短显着相关(HR = 1.52 [95% CI,1.10-2.09],P = 0.011)。 BRCA 中 MND1 的上调在外部队列和临床样本中得到了验证。生存分析表明,MND1 表达升高与 BRCA 患者生存率降低相关。鉴定了 MND1 的共表达基因,随后基于显着相关基因的通路分析表明 MND1 在 DNA 复制、细胞周期调节和 DNA 损伤修复中发挥关键作用。观察到的 MND1 异常升高和激活导致 BRCA 细胞增殖和迁移增加,同时细胞凋亡减少。MND1 成为多种癌症(包括 BRCA)诊断和治疗靶向的有前途的生物标志物。 MND1 的异常上调和激活与 BRCA 患者的致癌和不良预后有关,这可能归因于其参与 HR 依赖性 ALT,值得进一步审查。版权所有 © 2024 作者。由爱思唯尔公司出版。保留所有权利。
The aberrant up-regulation of meiotic nuclear division 1 (MND1) in somatic cells is considered as one of the driving factors of oncogenesis, whereas its expression and role in breast invasive cancer (BRCA) remain unclear. Hence, this study embarked on a comprehensive evaluation of MND1 across various cancers and identified its roles in BRCA.Based on publicly available databases, including but not limited to UCSC Xena, TCGA, GTEx, GEO, STRING, GeneMANIA, and CancerSEA, we evaluated the expression patterns, genomic features, and biological functions of MND1 from a pan-cancer viewpoint and delved into the implications of MND1 in the prognosis and treatment of BRCA. Further molecular biology experiments were undertaken to identify the role of MND1 in proliferation, migration, and apoptosis in BRCA cells.Elevated levels of MND1 were notably observed in a wide array of tumor types, especially in BRCA, COAD, HNSC, LIHC, LUAD, LUSC, STAD, and UCEC. Elevated MND1 expression was markedly associated with shortened OS in several tumors, including BRCA (HR = 1.52 [95%CI, 1.10-2.09], P = 0.011). The up-regulation of MND1 in BRCA was validated in external cohorts and clinical samples. Survival analyses demonstrated that elevated MND1 expression was associated with decreased survival for patients with BRCA. Co-expressed genes of MND1 were identified, and subsequent pathway analyses based on significantly associated genes indicated that MND1 plays key roles in DNA replication, cell cycle regulation, and DNA damage repair. The observed abnormal elevation and activation of MND1 led to increased proliferation and migration, along with decreased apoptosis in BRCA cells.MND1 emerges as a promising biomarker for diagnostic and therapeutic targeting in various cancers, including BRCA. The abnormal up-regulation and activation of MND1 are linked to carcinogenesis and poor prognosis among BRCA patients, which may be attributed to its involvement in HR-dependent ALT, warranting further scrutiny.Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.