Department of Gynecology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China.
Sun Yat-sen University Cancer Center, Sun Yat-sen University State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, China.
Neoplasma. 2024 Aug;71(4):319-332. doi: 10.4149/neo_2024_240127N41.
Protein lactylation has a poor prognosis in malignant tumors, but its impact on the prognosis of epithelial ovarian cancer (EOC) remains unknown. We analyzed 112 patients with EOC. Immunohistochemical staining was used to detect the level of pan lactylation (Pan Kla) and histone H3K18 lactylation (H3K18la) in the EOC tissues and normal ovarian tissues. The result showed that the protein lactylation level in EOC was higher than in normal tissues. Then, we analyzed the relationship between overall survival (OS), progression-free survival (PFS) of EOC, and lactylation. The result showed that patients with high histone H3K18la levels had poorer OS (p=0.028) and PFS (p<0.001). Multivariate Cox regression analysis of PFS showed histone H3K18la was an independent risk factor (p=0.001). In addition, we found that both histone H3K18la and Pan Kla in the cytoplasm were associated with platinum recurrence time (p=0.002/p=0.003). The results also indicated that the H3K18la level was related to a tumor stage (p=0.037). Furthermore, we explored the effects of lactylation on the metastasis of ovarian cancer. The results indicated a significant increase in migration in the promoter group compared to the negative control group and inhibitor group. In conclusion, high histone H3K18la level is associated with poor prognosis in EOC. Protein lactylation may have a significant impact on EOC and could potentially be used as a target for EOC therapy in the future.
蛋白质乳酰化在恶性肿瘤中预后不良,但它对上皮性卵巢癌(EOC)预后的影响尚不清楚。我们分析了 112 例 EOC 患者。免疫组织化学染色用于检测 EOC 组织和正常卵巢组织中泛乳酰化(Pan Kla)和组蛋白 H3K18 乳酰化(H3K18la)的水平。结果表明,EOC 中的蛋白质乳酰化水平高于正常组织。然后,我们分析了 EOC 的总生存期(OS)、无进展生存期(PFS)与乳酰化的关系。结果表明,组蛋白 H3K18la 水平高的患者 OS(p=0.028)和 PFS(p<0.001)较差。PFS 的多变量 Cox 回归分析表明,组蛋白 H3K18la 是一个独立的危险因素(p=0.001)。此外,我们发现细胞质中的组蛋白 H3K18la 和 Pan Kla 均与铂类复发时间有关(p=0.002/p=0.003)。结果还表明,H3K18la 水平与肿瘤分期有关(p=0.037)。此外,我们探讨了乳酰化对卵巢癌转移的影响。结果表明,与阴性对照组和抑制剂组相比,启动子组的迁移明显增加。总之,组蛋白 H3K18la 水平与 EOC 的不良预后相关。蛋白质乳酰化可能对 EOC 有显著影响,未来可能成为 EOC 治疗的靶点。