Wichmann Gunnar, Herchenhahn Cindy, Boehm Andreas, Mozet Christian, Hofer Mathias, Fischer Milos, Kolb Marlen, Dietz Andreas
Clinic for Otorhinolaryngology, Head and Neck Surgery, University Hospital Leipzig, Liebigstr. 10-14, 04103 Leipzig, Germany; LIFE - Leipzig Research Center for Civilization Diseases, University of Leipzig, Philipp-Rosenthal-Str. 21, 04103 Leipzig, Germany. Electronic address: http://www.uni-leipzig.de/~hno/.
Clinic for Otorhinolaryngology, Head and Neck Surgery, University Hospital Leipzig, Liebigstr. 10-14, 04103 Leipzig, Germany; Clinic for Anesthesiology and Intensive Care, University Hospital Leipzig, Liebigstr. 20, 04103 Leipzig, Germany.
Oral Oncol. 2017 Jun;69:115-127. doi: 10.1016/j.oraloncology.2017.04.017. Epub 2017 May 8.
Personalized medicine and treatment stratification of patients with head and neck squamous cell carcinoma (HNSCC) today mostly ignore genetic heterogeneity in HNSCC but especially the patient's genetic background. We hypothesized that particular human leukocyte antigen (HLA) class I (HLA-A, B, Cw) and II proteins (DR, DQ) confer susceptibility for and influence development of HNSCC and may be prognostic factors for progression-free survival (PFS).
90 consecutive HNSCC patients of the prospective observational cohort study LIFE treated between 08/2010 and 05/2011 at the University Leipzig underwent low resolution typing of HLA-A, B, Cw, DR, and DQ. Antigen and haplotype frequencies were compared to those in German blood donors. Effects on PFS were analyzed using Kaplan-Meier curves and Cox models.
HNSCC patients had overall altered HLA-B frequencies (P<0.05); frequencies of B∗44 were lower, those of B∗13, B∗52, and B∗57 increased (P<0.05). Almost all other antigen frequencies showed no deviation. Homozygous HLA-Cw and DRB4 were frequent and associated with reduced PFS (P<0.05). Altered haplotype frequencies were common and particular haplotypes accompanied by differing PFS. B∗13/Cw∗06 carriers had poorest outcome (P=0.011). However, multivariate Cox proportional hazard models revealed 3 clinical covariates (localization oropharynx, loco-regional metastasis, and T4 category), HPV16-DNA positivity, and 10 HLA traits as independent predictors for PFS.
The relevance of the genetic background of HNSCC patients calls for future research to clarify the role of HLA traits in HNSCC and if PFS depends on HLA.
如今，头颈部鳞状细胞癌（HNSCC）患者的个性化医疗和治疗分层大多忽略了HNSCC中的基因异质性，尤其是患者的基因背景。我们推测，特定的人类白细胞抗原（HLA）I类（HLA - A、B、Cw）和II类蛋白（DR、DQ）会增加HNSCC的易感性并影响其发展，且可能是无进展生存期（PFS）的预后因素。
2010年8月至2011年5月在莱比锡大学接受治疗的前瞻性观察队列研究LIFE中的90例连续HNSCC患者接受了HLA - A、B、Cw、DR和DQ的低分辨率分型。将抗原和单倍型频率与德国献血者的频率进行比较。使用Kaplan - Meier曲线和Cox模型分析对PFS的影响。
HNSCC患者的HLA - B频率总体发生改变（P<0.05）；B∗44的频率较低，B∗13、B∗52和B∗57的频率增加（P<0.05）。几乎所有其他抗原频率均无偏差。纯合子HLA - Cw和DRB4很常见，且与PFS降低相关（P<0.05）。单倍型频率改变很常见，特定单倍型伴随着不同的PFS。B∗13/Cw∗06携带者的预后最差（P = 0.011）。然而，多变量Cox比例风险模型显示3个临床协变量（口咽定位、局部区域转移和T分期类别）、HPV16 - DNA阳性以及10个HLA特征是PFS的独立预测因素。
HNSCC患者基因背景的相关性要求未来开展研究，以阐明HLA特征在HNSCC中的作用以及PFS是否依赖于HLA。
