Tian Ye, Zhu Kongjun, Li Yuefei, Ren Zhen, Wang Juan
Department of Thyroid and Breast Surgery Wuhan No. 1 Hospital, Wuhan, Hubei, China.
Department of Blood Transfusion, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan, Hubei, China.
Am J Transl Res. 2022 Nov 15;14(11):7670-7688. eCollection 2022.
Microtubule actin cross-linking factor 1 (MACF1) mutations are known to play an important role in the progression of various cancers. However, its role in breast cancer remains to be determined. In this study, we investigated how MACF1 mutations may play a role in breast cancer development.
The gene-expression profile data of patients with breast cancer were obtained from The Cancer Genome Atlas (TCGA)-Breast cancer cohort. We estimated the influence of MACF1 mutations on patient clinical prognosis using the Kaplan-Meier method. Further, patients with MACF1-mutant (MACF1-MT) and MACF1-wild-type (MACF1-WT) were compared to identify the differentially expressed genes (DEGs). We also performed functional enrichment analyses, constructed protein-protein interaction (PPI) and competing endogenous RNA (ceRNA) networks, and investigated the correlation between MACF1 mutations and immune-cell infiltration. To explore the prognostic value of MACF1 mutations, a nomogram was developed based on MACF1 mutations and other clinicopathological parameters.
Patients with MACF1-MT had a worse prognosis and higher tumor mutation burden score (P < 0.05) than patients with MACF1-WT. MACF1 mutations were demonstrated to upregulate the mTOR signaling pathway and alter energy metabolism and tumor immune microenvironment. Thus, MACF1 mutations might affect immunogenicity and result in a lower response to immunotherapy. By analyzing the Genomics of Drug Sensitivity in Cancer (GDSC), the sensitivity of breast cancer cells to 13 drugs was found to be significantly enhanced by MACF1 mutations. The prognostic model was verified in predicting the outcome of breast cancer patients.
MACF1 mutations might be a potential prognostic biomarker and a therapeutic target for breast cancer.
已知微管肌动蛋白交联因子1（MACF1）突变在多种癌症的进展中起重要作用。然而，其在乳腺癌中的作用仍有待确定。在本研究中，我们调查了MACF1突变如何在乳腺癌发展中发挥作用。
从癌症基因组图谱（TCGA）-乳腺癌队列中获取乳腺癌患者的基因表达谱数据。我们使用Kaplan-Meier方法评估MACF1突变对患者临床预后的影响。此外，比较MACF1突变型（MACF1-MT）和MACF1野生型（MACF1-WT）患者以鉴定差异表达基因（DEG）。我们还进行了功能富集分析，构建了蛋白质-蛋白质相互作用（PPI）和竞争性内源性RNA（ceRNA）网络，并研究了MACF1突变与免疫细胞浸润之间的相关性。为了探索MACF1突变的预后价值，基于MACF1突变和其他临床病理参数开发了列线图。
与MACF1-WT患者相比，MACF1-MT患者预后更差，肿瘤突变负担评分更高（P<0.05）。MACF1突变被证明可上调mTOR信号通路并改变能量代谢和肿瘤免疫微环境。因此，MACF1突变可能影响免疫原性并导致对免疫治疗的反应降低。通过分析癌症药物敏感性基因组学（GDSC），发现MACF1突变可显著增强乳腺癌细胞对13种药物的敏感性。该预后模型在预测乳腺癌患者的结局方面得到了验证。
MACF1突变可能是乳腺癌的潜在预后生物标志物和治疗靶点。
