Han Susu, Huang Tao, Li Wen, Wang Xiyu, Wu Xing, Liu Shanshan, Yang Wei, Shi Qi, Li Hongjia, Hou Fenggang
Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
The Affiliated Hospital of Ningbo University, Ningbo, China.
Front Oncol. 2019 Feb 6;9:39. doi: 10.3389/fonc.2019.00039. eCollection 2019.
Cancer stem cell marker CD44 and its variant isoforms (CD44v) may be correlated with tumor growth, metastasis, and chemo-radiotherapy resistance. However, the prognostic power of CD44 and CD44v in advanced cancer remains controversial. Therefore, the purpose of our study was to generalize the prognostic significance of these cancer stem cell markers in advanced cancer patients. Hazard ratios (HRs) with 95% confidence intervals (95% CIs) were calculated from multivariable analysis to assess the associations among CD44, CD44v6, and CD44v9 positivity and overall survival (OS), disease-free survival (DFS), progression-free survival (PFS), cancer-specific survival (CSS), and recurrence-free survival (RFS). Trial sequential analysis (TSA) was also conducted. We included 15 articles that reported on 1,201 patients with advanced cancer (CD44: nine studies with 796 cases, CD44v6: three studies with 143 cases, and CD44v9: three studies with 262 cases). CD44 expression was slightly linked to worse OS (HR = 2.03, = 0.027), but there was no correlation between CD44 expression and DFS, RFS, or PFS. Stratified analysis showed that CD44 expression was not correlated with OS at ≥5 years or OS in patients receiving adjuvant therapy. CD44v6 expression was not associated with OS. CD44v9 expression was closely associated with poor 5-years CSS in patients treated with chemo/radiotherapy (HR = 3.62, < 0.001). However, TSA suggested that additional trials were needed to confirm these conclusions. CD44 or CD44v9 might be novel therapeutic targets for improving the treatment of advanced cancer patients. Additional prospective clinical trials are strongly needed across different cancer types.
癌症干细胞标志物CD44及其可变剪接异构体（CD44v）可能与肿瘤生长、转移及放化疗耐药相关。然而，CD44和CD44v在晚期癌症中的预后价值仍存在争议。因此，我们研究的目的是总结这些癌症干细胞标志物在晚期癌症患者中的预后意义。通过多变量分析计算风险比（HRs）及其95%置信区间（95% CIs），以评估CD44、CD44v6和CD44v9阳性与总生存期（OS）、无病生存期（DFS）、无进展生存期（PFS）、癌症特异性生存期（CSS）及无复发生存期（RFS）之间的关联。同时进行了序贯试验分析（TSA）。我们纳入了15篇报道1201例晚期癌症患者的文章（CD44：9项研究共796例，CD44v6：3项研究共143例，CD44v9：3项研究共262例）。CD44表达与较差的OS略有关联（HR = 2.03， = 0.027），但CD44表达与DFS、RFS或PFS之间无相关性。分层分析显示，CD44表达与≥5年的OS或接受辅助治疗患者的OS无关。CD44v6表达与OS无关。CD44v9表达与接受放化疗患者较差的5年CSS密切相关（HR = 3.62， < 0.001）。然而，TSA提示需要更多试验来证实这些结论。CD44或CD44v9可能是改善晚期癌症患者治疗的新治疗靶点。强烈需要针对不同癌症类型开展更多前瞻性临床试验。
