Yang Xian-Yan, Zheng Xiao-Xia, Zhai Xue-Jia, Tang Tao, Yu Shi-Cang
Department of Stem Cell and Regenerative Medicine, Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University), ChongQing, China.
Key Laboratory of Cancer Immunopathology, Ministry of Education, ChongQing, China.
Proteomics Clin Appl. 2024 Jul;18(4):e202300002. doi: 10.1002/prca.202300002. Epub 2024 Feb 5.
Triple-negative breast cancer (TNBC) has a poor prognosis, an ineffective diagnosis, and a high degree of aggressiveness. Therefore, novel therapeutic targets for TNBC urgently need to be identified.
Through a series of bioinformatics analyses, including analysis of differential gene expression, protein-protein interaction (PPI) network, univariate cox regression, immune infiltration, pathway enrichment, etc, as well as auxiliary immunohistochemistry (IHC) and protein quantitativae analysis, to explore prognostic marker for TNBC.
In TNBC tissues, we found that SPDL1 (CCDC99) was considerably overexpressed at both the mRNA and protein levels compared to that in normal and non-TNBC tissues. Additionally, we found that SPDL1-high expression was strongly linked to poor prognosis in TNBC patients. Excessive SPDL1 expression was positively correlated with tumor growth and strongly linked to the cell cycle, DNA replication, and the p53 signaling pathway. In addition, CIBERSORT analysis revealed that SPDL1 can affect the tumor immune microenvironment (TME) in TNBC, encourage the development of TNBC and act as a potential prognostic biomarker for TNBC. Patients with SPDL1-high expression were more sensitive to AZD8055. Notably, we discovered that SPDL1 is highly expressed in the majority of malignancies and may have an impact on the pancancer prognosis.
SPDL1 can serve as a novel prognostic marker for TNBC and pancancer patients.
三阴性乳腺癌(TNBC)预后较差,诊断效果不佳,且具有高度侵袭性。因此,迫切需要确定TNBC的新型治疗靶点。
通过一系列生物信息学分析,包括差异基因表达分析、蛋白质-蛋白质相互作用(PPI)网络分析、单变量cox回归分析、免疫浸润分析、通路富集分析等,以及辅助免疫组织化学(IHC)和蛋白质定量分析,来探索TNBC的预后标志物。
在TNBC组织中,我们发现与正常组织和非TNBC组织相比,SPDL1(CCDC99)在mRNA和蛋白质水平均显著过表达。此外,我们发现SPDL1高表达与TNBC患者的不良预后密切相关。SPDL1表达过多与肿瘤生长呈正相关,并与细胞周期、DNA复制和p53信号通路密切相关。此外,CIBERSORT分析显示,SPDL1可影响TNBC中的肿瘤免疫微环境(TME),促进TNBC的发展,并作为TNBC的潜在预后生物标志物。SPDL1高表达的患者对AZD8055更敏感。值得注意的是,我们发现SPDL1在大多数恶性肿瘤中高表达,可能会影响泛癌预后。
SPDL1可作为TNBC和泛癌患者的新型预后标志物。