Aarstad Helene Hersvik, Moe Svein Erik Emblem, Bruserud Øystein, Lybak Stein, Aarstad Hans Jørgen, Tvedt Tor Henrik Anderson
Department of Clinical Science, Faculty of Medicine, University of Bergen, 5021 Bergen, Norway.
Department of Otolaryngology/Head and Neck Surgery, Haukeland University Hospital, 5021 Bergen, Norway.
Biomedicines. 2020 Oct 14;8(10):418. doi: 10.3390/biomedicines8100418.
C-reactive protein (CRP) has a prognostic impact in head and neck squamous cell carcinoma (HNSCC). However, the acute phase reaction involves many other proteins depending on its inducing events, including various cytokines that can function as reaction inducers. In the present study, we compared the pretreatment acute phase cytokine profile for 144 patients with potentially curative HNSCC. We investigated the systemic levels of interleukin (IL)6 family mediators (glycoprotein (gp130), IL6 receptor (R)α, IL6, IL27, IL31, oncostatin M (OSM), ciliary neurotrophic factor (CNTF)), IL1 subfamily members (IL1R antagonist (A), IL33Rα), and tumor necrosis factor (TNF)α. Patient subsets identified from this 10-mediator profile did not differ with regard to disease stage, human papilloma virus (HPV) status, CRP levels, or death cause. Increased CRP, IL6, and IL1RA levels were independent markers for HNSCC-related death in the whole patient population. Furthermore, gp130, IL6Rα, and IL31 were suggested to predict prognosis among tumor HPV-negative patients. Only IL6 predicted survival in HPV-positive patients. Finally, we did a clustering analysis of HPV-negative patients based on six acute phase mediators that showed significant or borderline association with prognosis in Kaplan-Meier analyses; three subsets could then be identified, and they differed in survival ( < 0.001). To conclude, (i) HPV-negative and HPV-positive HNSCC patients show similar variations of their systemic acute phase profiles; (ii) the prognostic impact of single mediators differs between these two patient subsets; and (iii) for HPV-negative patients, acute phase profiling identifies three patient subsets that differ significantly in survival.
C反应蛋白（CRP）对头颈部鳞状细胞癌（HNSCC）具有预后影响。然而，急性期反应还涉及许多其他蛋白质，这取决于其诱导事件，包括各种可作为反应诱导剂的细胞因子。在本研究中，我们比较了144例潜在可治愈性HNSCC患者的预处理急性期细胞因子谱。我们研究了白细胞介素（IL）6家族介质（糖蛋白（gp130）、IL6受体（R）α、IL6、IL27、IL31、抑瘤素M（OSM）、睫状神经营养因子（CNTF））、IL1亚家族成员（IL1R拮抗剂（A）、IL33Rα）和肿瘤坏死因子（TNF）α的全身水平。从这10种介质谱中确定的患者亚组在疾病分期、人乳头瘤病毒（HPV）状态、CRP水平或死亡原因方面没有差异。CRP、IL6和IL1RA水平升高是整个患者群体中HNSCC相关死亡的独立标志物。此外，gp130、IL6Rα和IL31被认为可预测肿瘤HPV阴性患者的预后。只有IL6可预测HPV阳性患者的生存情况。最后，我们基于在Kaplan-Meier分析中与预后显示出显著或临界关联的六种急性期介质对HPV阴性患者进行了聚类分析；然后可以识别出三个亚组，它们在生存率方面存在差异（<0.001）。总之，（i）HPV阴性和HPV阳性HNSCC患者的全身急性期谱变化相似；（ii）这两个患者亚组中单一介质的预后影响不同；（iii）对于HPV阴性患者，急性期谱分析可识别出三个在生存率方面有显著差异的患者亚组。
