Department of Oncology, The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong, China.
The First Clinical Medical College, Southern Medical University, Guangzhou, China.
PeerJ. 2023 Oct 11;11:e15475. doi: 10.7717/peerj.15475. eCollection 2023.
Breast cancer (BRCA) is the most diagnosed cancer worldwide and is responsible for the highest cancer-associated mortality among women. It is evident that anoikis resistance contributes to tumour cell metastasis, and this is the primary cause of treatment failure for BRCA. However, anoikis-related gene (ARG) expression profiles and their prognostic value in BRCA remain unclear. In this study, a prognostic model of ARGs based on The Cancer Genome Atlas (TCGA) database was established using a least absolute shrinkage and selection operator analysis to evaluate the prognostic value of ARGs in BRCA. The risk factor graph demonstrated that the low-risk group had longer survival than the high-risk group, implying that the prognostic model had a good performance. We identified 11 ARGs that exhibited differential expression between the two risk groups in TCGA and Gene Expression Omnibus databases. Through Gene Ontology and Kyoto Encyclopaedia of Genes and Genomes enrichment analyses, we revealed that the screened ARGs were associated with tumour progression and metastasis. In addition, a protein-protein interaction network showed potential interactions among these ARGs. Furthermore, gene set enrichment analysis suggested that the Notch and Wnt signalling pathways were overexpressed in the high-risk group, and gene set variation analysis revealed that 38 hallmark genes differed between the two groups. Moreover, Kaplan-Meier survival curves and receiver operating characteristic curves were used to identify five ARGs (CD24, KRT15, MIA, NDRG1, TP63), and quantitative polymerase chain reaction was employed to assess the differential expression of these ARGs. Univariate and multivariate Cox regression analyses were then performed for the key ARGs, with the best prediction of 3 year survival. In conclusion, ARGs might play a crucial role in tumour progression and serve as indicators of prognosis in BRCA.
乳腺癌(BRCA)是全球最常见的癌症,也是女性癌症相关死亡率最高的癌症。显然,抗失巢凋亡能力促进肿瘤细胞转移,这是 BRCA 治疗失败的主要原因。然而,BRCA 中与失巢凋亡相关的基因(ARG)表达谱及其预后价值尚不清楚。本研究基于癌症基因组图谱(TCGA)数据库,采用最小绝对收缩和选择算子分析建立了 ARG 预后模型,评估 ARG 在 BRCA 中的预后价值。风险因子图表明,低危组的生存时间长于高危组,提示预后模型性能良好。我们在 TCGA 和基因表达综合数据库中鉴定了两组间差异表达的 11 个 ARG。通过基因本体论和京都基因与基因组百科全书富集分析,我们发现筛选出的 ARG 与肿瘤进展和转移有关。此外,蛋白质-蛋白质相互作用网络显示这些 ARG 之间存在潜在的相互作用。进一步的基因集富集分析表明,高危组中 Notch 和 Wnt 信号通路过度表达,基因集变异分析显示两组间有 38 个特征基因存在差异。此外,Kaplan-Meier 生存曲线和受试者工作特征曲线用于识别 5 个 ARG(CD24、KRT15、MIA、NDRG1、TP63),并采用定量聚合酶链反应评估这些 ARG 的差异表达。然后对关键 ARG 进行单因素和多因素 Cox 回归分析,以最佳预测 3 年生存率。总之,ARG 可能在肿瘤进展中发挥重要作用,并可作为 BRCA 预后的指标。