Induction of CD44 Variant 9-Expressing Cancer Stem Cells Might Attenuate the Efficacy of Chemoradioselection and Worsens the Prognosis of Patients with Advanced Head and Neck Cancer
Induction of CD44 Variant 9-Expressing Cancer Stem Cells Might Attenuate the Efficacy of Chemoradioselection and Worsens the Prognosis of Patients with Advanced Head and Neck Cancer
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DOI：
10.1371/journal.pone.0116596
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发表时间：
2015-03-09
期刊：
影响因子：
3.7
通讯作者：
Masuda, Muneyuki
中科院分区：
文献类型：
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作者：
Aso, Takeichiro;Matsuo, Mioko;Masuda, Muneyuki
在我们研究所，根据患者对初始30-40 Gy同步放化疗（CCRT）的反应，采用放化疗选择策略来选择器官保存患者。具有良好反应（即放化疗选择性，CRS）的患者比具有不良反应（即非放化疗选择性，N-CRS）的患者表现出更好的结果。成功的靶向分子削弱了放射线选择的功效可能会改善结果。因此，本研究的目的是评估一种新的癌症干细胞（CSC）标志物CD44变体9 （CD44v9）与晚期头颈部鳞状细胞癌（HNSCC）放化疗的细胞难治性之间的关系。材料与方法通过医学图表检索，收集了1997 ~ 2008年接受放化疗的晚期HNSCC患者102例。根据我们的算法，30例患者为诱导CCRT后的CRC， 72例为N-CRS。采用常规免疫组化技术，用抗cd44v9特异性抗体对活检标本和手术切除的肿瘤标本进行免疫染色。结果活检标本中CD44v9的内在表达水平与放化疗选择和患者生存无关。然而，在N-CRS患者中，cd44v9阳性组的预后明显差于cd44v9阴性组（P = 0.008）。多因素分析显示，在T、N、对CCRT的反应、CD44v9 4个候选因素中，CD44v9阳性（HR: 3.145, 95% CI: 1.235 ~ 8.008, P = 0.0163）与预后不良及N期进展显著相关（HR: 3.525, 95% CI: 1.054 ~ 9.060, P = 0.0228）。此外，cd44v9诱导组的存活率显著低于cd44v9未诱导组（P = 0.04）。结论sccrt诱导cd44v9表达的CSCs似乎是放化疗选择的主要障碍。靶向cd44v9似乎是一种很有前途的策略，可以提高放化疗的有效性和随之而来的器官保存和生存。
BackgroundAt our institute, a chemoradioselection strategy has been used to select patients for organ preservation on the basis of response to an initial 30-40 Gy concurrent chemoradiotherapy (CCRT). Patients with a favorable response (i.e., chemoradioselected; CRS) have demonstrated better outcomes than those with an unfavorable response (i.e., nonchemoradioselected; N-CRS). Successful targeting of molecules that attenuate the efficacy of chmoradioselection may improve results. Thus, the aim of this study was to evaluate the association of a novel cancer stem cell (CSC) marker, CD44 variant 9 (CD44v9), with cellular refractoriness to chemoradioselection in advanced head and neck squamous cell carcinoma (HNSCC).Materials and MethodsThrough a medical chart search, 102 patients with advanced HNSCC treated with chemoradioselection from 1997 to 2008 were enrolled. According to our algorithm, 30 patients were CRC following induction CCRT and 72 patients were N-CRS. Using the conventional immunohistochemical technique, biopsy specimens and surgically removed tumor specimens were immunostained with the anti-CD44v9 specific antibodies.ResultsThe intrinsic expression levels of CD44v9 in the biopsy specimens did not correlate with the chemoradioselection and patient survival. However, in N-CRS patients, the CD44v9-positive group demonstrated significantly (P = 0.008) worse prognosis, than the CD44v9-negative group. Multivariate analyses demonstrated that among four candidate factors (T, N, response to CCRT, and CD44v9), CD44v9 positivity (HR: 3.145, 95% CI: 1.235-8.008, P = 0.0163) was significantly correlated with the poor prognosis, along with advanced N stage (HR: 3.525, 95% CI: 1.054-9.060, P = 0.0228). Furthermore, the survival rate of the CD44v9-induced group was significantly (P = 0.04) worse than the CD44v9-non-induced group.ConclusionsCCRT-induced CD44v9-expressing CSCs appear to be a major hurdle to chemoradioselection. CD44v9-targeting seems to be a promising strategy to enhance the efficacy of chemoradioselection and consequent organ preservation and survival.