Zhang Nuan, Wang Zhipeng, Zhang Yang
Shandong University of Traditional Chinese Medicine Affiliated Hospital, Department of Oncology, Jinan, Shandong, China.
Shandong University of Traditional Chinese Medicine Affiliated Hospital, Department of Pulmonary and Critical Care Medicine, Jinan, Shandong, China.
J Med Biochem. 2025 Aug 21;44(5):935-944. doi: 10.5937/jomb0-56147.
To assess the predictive value of drug-resistant proteins - serum glutathione S-transferase (GST-â), P-glycoprotein (PGP), P53, Ki-67 - in triple-negative breast cancer (TNBC) and their role in chemotherapy resistance. This systematic review and meta-analysis aimed to explore their clinical relevance for improving TNBC treatment outcomes.
We systematically searched PubMed, Web of Science, CNKI, WanFang, and VIP databases for studies from 2010 to 2024. Studies meeting predefined inclusion and exclusion criteria were selected. Data extraction and quality assessment were performed by two independent researchers. Meta-analysis was conducted using RevMan 5.3 software.
Seven studies were included, involving 1,772 patients, with 745 TNBC cases and 1,027 non-TNBC cases. Meta-analysis showed that in TNBC compared to non-TNBC, the expression rates of GST-â [O R= 3.41, 95% CI (2.21, 5.25), P< 0.00001], PGP [O R= 1.87, 95% CI (1.17, 2.98), P= 0.008], P53 [O R= 3.65, 95% CI (2.25, 5.91), P< 0.00001], and Ki-67 [O R= 1.19, 95% CI (0.54, 1.84), P= 0.0004] were significantly elevated, indicating higher drug resistance. However, no significant differences were found in Topo I, II, or III expression. Additionally, TNBC patients had poorer disease-free survival (DFS) [O R = 0.30, 95% CI (0.15, 0.59), P=0.0005] and overall survival (OS) [O R=0.17, 95% CI (0.11, 0.28), P<0.00001] compared to non-TNBC patients.
The elevated expression of drug-resistant proteins GST-â, PGP P53, and Ki-67 in TNBC suggests that these biomarkers are closely associated with chemotherapy resistance. Monitoring their levels during treatment may help guide more effective clinical strategies for managing TNBC. The findings emphasise the need for personalised therapeutic approaches based on protein expression profiles to improve clinical outcomes for TNBC patients.
评估耐药蛋白——血清谷胱甘肽S-转移酶（GST-π）、P-糖蛋白（PGP）、P53、Ki-67——在三阴性乳腺癌（TNBC）中的预测价值及其在化疗耐药中的作用。本系统评价和荟萃分析旨在探讨它们对改善TNBC治疗结果的临床相关性。
我们系统检索了PubMed、Web of Science、中国知网、万方和维普数据库中2010年至2024年的研究。选择符合预定义纳入和排除标准的研究。由两名独立研究人员进行数据提取和质量评估。使用RevMan 5.3软件进行荟萃分析。
纳入7项研究，涉及1772例患者，其中TNBC病例745例，非TNBC病例1027例。荟萃分析显示，与非TNBC相比，TNBC中GST-π的表达率[比值比（OR）=3.41，95%置信区间（CI）（2.21，5.25），P<0.00001]、PGP的表达率[OR=1.87，95%CI（1.17，2.98），P=0.008]、P53的表达率[OR=3.65，95%CI（2.25，5.91），P<0.00001]和Ki-67的表达率[OR=1.19，95%CI（0.54，1.84），P=0.0004]显著升高，表明耐药性更高。然而，拓扑异构酶I、II或III的表达未发现显著差异。此外，与非TNBC患者相比，TNBC患者的无病生存期（DFS）[OR = 0.30，95%CI（0.15，0.59），P=0.0005]和总生存期（OS）[OR=0.17，95%CI（0.11，0.28），P<0.00001]较差。
TNBC中耐药蛋白GST-π、PGP、P53和Ki-67的表达升高表明这些生物标志物与化疗耐药密切相关。在治疗期间监测它们的水平可能有助于指导更有效的TNBC临床管理策略。研究结果强调需要基于蛋白质表达谱的个性化治疗方法来改善TNBC患者的临床结局。
