Ou Zhengrong, Fu Shoushuo, Yi Jian, Huang Jingxuan, Zhu Weidong
Ward Two, Department of General Surgery, Yueyang Hospital Affiliated to Hunan Normal University, Yueyang, Hunan 414000, P.R. China.
Department of Respiratory and Critical Care Medicine, Yueyang Hospital Affiliated to Hunan Normal University, Yueyang, Hunan 414000, P.R. China.
Oncol Lett. 2024 Sep 6;28(5):536. doi: 10.3892/ol.2024.14669. eCollection 2024 Nov.
The expression of cancer stem cell (CSC) markers adversely affect the survival prognosis of patients with hepatocellular carcinoma (HCC), but it is not clear which cancer stem cell marker has the best predictive effect on the survival prognosis and diagnostic value indicators of patients with HCC. Therefore, the present study performed a network meta-analysis to compare the prognostic and diagnostic value of the expressions of several CSC markers for patients with HCC and to identify the most efficient CSC marker. Studies on the associations of positive CSC markers with the overall survival (OS) rate, disease-free survival (DFS) rate, recurrence-free survival (RFS) rate, recurrence rate, differentiation, microvascular invasion and metastasis in patients with HCC were included in the network meta-analysis following searches on the PubMed, Embase, Elsevier and The Cochrane Library databases from January 1, 2013 to November 17, 2023. The Quality Assessment of Diagnostic Accuracy Studies-2 tool was used to assess the quality assessment of studies, and R (version 4.3.1), Stata (version 15.0) and Review Manager (version 5.3) were used for analysis. A total of 37 studies involving 3,980 participants were included. For patients with HCC, simultaneous positivity of cytokeratin 19 (CK19) and epithelial cell adhesion molecule (EpCAM) was the strongest predictor of the OS rate [surface under the cumulative ranking curve (SUCRA), 78.65%], positive keratin 19 (K19) was the strongest predictor of the RFS and DFS rates (SUCRA, 98.93 and 84.95%, respectively), and simultaneous positivity of EpCAM and cluster of differentiation (CD)90 was the strongest predictor of the recurrence rate (SUCRA, 5.61%). In addition, positivity of CD56, K19 and CD133 had the best diagnostic efficacy for poor differentiation [superiority index, 7.4498; 95% confidence interval (CI): 0.3333, 13.0000], microvascular invasion (superiority index, 8.4777; 95% CI: 0.2308, 17.0000), and metastasis (superiority index, 5.6097; 95% CI: 0.3333, 11.0000), respectively. In conclusion, no single CSC marker possessed the best predictive effect on all indexes of survival prognosis and diagnosis of patients with HCC. In terms of survival prognosis, simultaneous positivity of CK19 and EpCAM demonstrated the strongest predictive effect on the OS rate, suggesting an association with a low OS rate in patients with HCC; positive K19 revealed the strongest predictive effect on the RFS rate and DFS rate, suggesting an association with low RFS and DFS rates in patients with HCC; and simultaneous positivity of EpCAM and CD90 had the strongest predictive effect on the recurrence rate, suggesting a high recurrence rate in patients with HCC patients. In terms of diagnostic value, CD56, K19 and CD133 were the strongest predictors of poor differentiation, microvascular invasion and metastasis, respectively. In the future, well-designed randomized controlled trials are required to further confirm these findings.
癌症干细胞(CSC)标志物的表达对肝细胞癌(HCC)患者的生存预后产生不利影响,但尚不清楚哪种癌症干细胞标志物对HCC患者的生存预后和诊断价值指标具有最佳预测效果。因此,本研究进行了一项网状Meta分析,以比较几种CSC标志物表达对HCC患者的预后和诊断价值,并确定最有效的CSC标志物。在对PubMed、Embase、Elsevier和Cochrane图书馆数据库进行检索后,纳入了关于CSC阳性标志物与HCC患者总生存(OS)率、无病生存(DFS)率、无复发生存(RFS)率、复发率、分化、微血管侵犯和转移之间关联的研究,检索时间范围为2013年1月1日至2023年11月17日。采用诊断准确性研究质量评估-2工具对研究进行质量评估,并使用R(版本4.3.1)、Stata(版本15.0)和Review Manager(版本5.3)进行分析。共纳入37项研究,涉及3980名参与者。对于HCC患者,细胞角蛋白19(CK19)和上皮细胞粘附分子(EpCAM)同时阳性是OS率的最强预测指标[累积排序曲线下面积(SUCRA),78.65%],角蛋白19(K19)阳性是RFS率和DFS率的最强预测指标(SUCRA分别为98.93%和84.95%),EpCAM和分化簇(CD)90同时阳性是复发率的最强预测指标(SUCRA,5.61%)。此外,CD56、K19和CD133阳性对低分化[优势指数,7.4498;95%置信区间(CI):0.3333,13.0000]、微血管侵犯(优势指数,8.4777;95%CI:0.2308,17.0000)和转移(优势指数,5.6097;95%CI:0.3333,11.0000)分别具有最佳诊断效能。总之,没有单一的CSC标志物对HCC患者生存预后和诊断的所有指标都具有最佳预测效果。在生存预后方面,CK19和EpCAM同时阳性对OS率显示出最强的预测效果,提示与HCC患者低OS率相关;K19阳性对RFS率和DFS率显示出最强的预测效果,提示与HCC患者低RFS率和DFS率相关;EpCAM和CD90同时阳性对复发率显示出最强的预测效果,提示HCC患者复发率高。在诊断价值方面,CD56、K19和CD133分别是低分化、微血管侵犯和转移的最强预测指标。未来,需要设计良好的随机对照试验来进一步证实这些发现。