Serum signature of hypoxia-regulated factors is associated with progression after induction therapy in head and neck squamous cell cancer.
Serum signature of hypoxia-regulated factors is associated with progression after induction therapy in head and neck squamous cell cancer.
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DOI：
10.1158/1535-7163.mct-09-1047
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发表时间：
2010-06
影响因子：
5.7
通讯作者：
Heymach JV
中科院分区：
文献类型：
--
作者：
Byers LA;Holsinger FC;Kies MS;William WN;El-Naggar AK;Lee JJ;Hu J;Lopez A;Tran HT;Yan S;Du Z;Ang KK;Glisson BS;Raso MG;Wistuba II;Myers JN;Hong WK;Papadimitrakopoulou V;Lippman SM;Heymach JV
肿瘤缺氧调节许多细胞因子和血管生成因子（CAF），并与头颈部鳞状细胞癌（HNSCC）的预后不良相关。血清CAF谱可以提供关于宿主和肿瘤的生物学、预后和对治疗的反应的信息。我们调查了38例接受卡铂、紫杉醇和西妥昔单抗II期试验诱导治疗的HNSCC患者的CAF。采用多重微珠法和酶联免疫吸附法检测32例患者的CAF。通过Wilcoxon秩和检验，基线和诱导后CAF水平与疾病进展（PD）和人乳头瘤病毒（HPV）状态相关。基线水平的8种低氧调节CAF（“高危特征”，包括血管内皮生长因子、白细胞介素-4和-8、骨桥蛋白、生长相关癌基因-α（Gro-α）、嗜酸性粒细胞趋化因子、粒细胞集落刺激因子和基质细胞衍生因子-1 α）与随后的PD相关。≥6/8个因素的升高与至进展时间较短密切相关（p=0.001），对PD的特异性为73%，敏感性为100%。从基线至第6周Gro-α升高也与PD相关。HPV阴性肿瘤患者的无进展生存期和总生存期较短（分别为p=0.012和0.046），但没有个体CAF与HPV状态相关。然而，在14例HPV阴性患者中，6例PD患者均观察到高危CAF特征，但仅2/14例无PD患者。总之，血清CAF谱，特别是在HPV阴性患者中，可能有助于识别那些复发风险最高的患者。
Tumor hypoxia regulates many cytokines and angiogenic factors (CAFs) and is associated with worse prognosis in head and neck squamous cell cancer (HNSCC). Serum CAF profiling may provide information regarding the biology of the host and tumor, prognosis, and response to therapy. We investigated 38 CAFs in HNSCC patients receiving induction therapy on a Phase II trial of carboplatin, paclitaxel, and cetuximab. CAFs were measured by multiplex bead assay and enzyme-linked immunosorbent assay in 32 patients. Baseline and post-induction CAF levels were correlated with disease progression (PD) and human papilloma virus (HPV) status by Wilcoxon rank sum test. Baseline levels of 8 hypoxia-regulated CAFs (the “high-risk signature” including vascular endothelial growth factor, interleukins-4 and -8, osteopontin, growth-related oncogene-α (Gro-α), eotaxin, granulocyte-colony stimulating factor, and stromal cell derived factor-1α) were associated with subsequent PD. Elevation in ≥6/8 factors was strongly associated with shorter time to progression (p=0.001) and was 73% specific and 100% sensitive for PD. Rising Gro-α from baseline to week six was also associated with PD. Progression free and overall survival were shorter in patients with HPV-negative tumors (p=0.012 and 0.046, respectively), but no individual CAF was associated with HPV-status. However, among 14 HPV-negative patients, the high-risk CAF signature was seen in all 6 patients with PD, but only 2/14 without PD. In conclusion, serum CAF profiling, particularly in HPV-negative patients, may be useful for identifying those at highest risk for recurrence.