Department of Clinical Pathology and Medical Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan.
Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
J Cell Mol Med. 2024 Mar;28(6):e18163. doi: 10.1111/jcmm.18163.
Malic enzyme (ME) genes are key functional metabolic enzymes playing a crucial role in carcinogenesis. However, the detailed effects of ME gene expression on breast cancer progression remain unclear. Here, our results revealed ME1 expression was significantly upregulated in breast cancer, especially in patients with oestrogen receptor/progesterone receptor-negative and human epidermal growth factor receptor 2-positive breast cancer. Furthermore, upregulation of ME1 was significantly associated with more advanced pathological stages (p < 0.001), pT stage (p < 0.001) and tumour grade (p < 0.001). Kaplan-Meier analysis revealed ME1 upregulation was associated with poor disease-specific survival (DSS: p = 0.002) and disease-free survival (DFS: p = 0.003). Multivariate Cox regression analysis revealed ME1 upregulation was significantly correlated with poor DSS (adjusted hazard ratio [AHR] = 1.65; 95% CI: 1.08-2.52; p = 0.021) and DFS (AHR, 1.57; 95% CI: 1.03-2.41; p = 0.038). Stratification analysis indicated ME1 upregulation was significantly associated with poor DSS (p = 0.039) and DFS (p = 0.038) in patients with non-triple-negative breast cancer (TNBC). However, ME1 expression did not affect the DSS of patients with TNBC. Biological function analysis revealed ME1 knockdown could significantly suppress the growth of breast cancer cells and influence its migration ability. Furthermore, the infiltration of immune cells was significantly reduced when they were co-cultured with breast cancer cells with ME1 knockdown. In summary, ME1 plays an oncogenic role in the growth of breast cancer; it may serve as a potential biomarker of progression and constitute a therapeutic target in patients with breast cancer.
苹果酸酶（ME）基因是关键的功能代谢酶，在致癌作用中起着至关重要的作用。然而，ME 基因表达对乳腺癌进展的详细影响尚不清楚。在这里，我们的结果表明 ME1 在乳腺癌中表达显著上调，尤其是在雌激素受体/孕激素受体阴性和人表皮生长因子受体 2 阳性的乳腺癌患者中。此外，ME1 的上调与更晚期的病理分期（p<0.001）、pT 分期（p<0.001）和肿瘤分级（p<0.001）显著相关。Kaplan-Meier 分析表明 ME1 的上调与不良的疾病特异性生存（DSS：p=0.002）和无病生存（DFS：p=0.003）相关。多变量 Cox 回归分析表明，ME1 的上调与不良的 DSS 显著相关（调整后的危险比 [AHR] = 1.65；95%CI：1.08-2.52；p=0.021）和 DFS（AHR，1.57；95%CI：1.03-2.41；p=0.038）。分层分析表明，ME1 的上调与非三阴性乳腺癌（TNBC）患者的不良 DSS（p=0.039）和 DFS（p=0.038）显著相关。然而，ME1 的表达并不影响 TNBC 患者的 DSS。生物学功能分析表明，ME1 敲低可显著抑制乳腺癌细胞的生长并影响其迁移能力。此外，当与 ME1 敲低的乳腺癌细胞共培养时，免疫细胞的浸润明显减少。总之，ME1 在乳腺癌的生长中发挥致癌作用；它可能作为进展的潜在生物标志物，并构成乳腺癌患者的治疗靶点。
