Differences in LC3B expression and prognostic implications in oropharyngeal and oral cavity squamous cell carcinoma patients.
Differences in LC3B expression and prognostic implications in oropharyngeal and oral cavity squamous cell carcinoma patients.
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DOI：
10.1186/s12885-018-4536-x
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发表时间：
2018-06-01
期刊：
影响因子：
3.8
通讯作者：
Lee CS
中科院分区：
文献类型：
--
作者：
Lai K;Matthews S;Wilmott JS;Killingsworth MC;Yong JL;Caixeiro NJ;Wykes J;Samakeh A;Forstner D;Lee M;McGuinness J;Niles N;Hong A;Ebrahimi A;Lee CS
本研究旨在探讨微管相关蛋白轻链3B（LC 3B）在口咽和口腔鳞状细胞癌（SCC）中的表达及其预后意义。LC 3B表达与人乳头瘤病毒（HPV）状态在口咽鳞癌中的预后意义也进行了研究。组织微阵列（TMAs）由福尔马林固定、石蜡包埋的口咽（n = 47）和口腔（n = 95）SCC组织块构建，这些SCC组织块来自具有长期复发和总生存数据（中位数= 47个月）的患者。通过免疫组化评估肿瘤上的LC 3B表达，并评估其与临床病理变量的相关性。使用ROC曲线和曼哈顿距离最小化将LC 3B表达分层为高表达和低表达队列，然后进行Kaplan-Meier和多变量生存分析。口咽鳞癌患者HPV状态和LC 3B表达之间的相互作用也通过联合效应和分层分析进行了研究。Kaplan-Meier生存率和单变量分析显示，LC 3B高表达与口咽部SCC患者的总体生存率差相关（分别为p = 0.007和HR = 3.18，95%CI 1.31-7.71，p = 0.01）。LC 3B高表达也是口咽鳞癌患者总体生存率差的独立预后因素（HR = 4.02，95%CI 1.38-11.47，p = 0.011）。相比之下，在口腔SCC中，在单变量分析后，只有无病生存期保持统计学显著性（HR = 2.36，95% CI 1.19-4.67，p = 0.014），尽管Kaplan-Meier生存分析显示高LC 3B表达与总体和无病生存期较差相关（分别为p = 0.046和0.011）。此外，HPV阴性/高LC 3B表达的口咽鳞癌患者在联合效应和分层显示中与总生存率差相关（分别为p = 0.024和0.032）。LC 3B高表达与口咽和口腔SCC的不良预后相关，这突出了自噬在这些恶性肿瘤中的重要性。LC 3B的高表达似乎是口咽部SCC的独立预后标志，但对口腔SCC患者不是。LC 3B在口咽和口腔SCC之间的预后意义的差异进一步支持了这些恶性肿瘤之间的生物学差异。HPV阴性且LC 3B高表达的口咽SCC患者可能面临不良结局的特殊风险，值得在更大数量的前瞻性研究中进一步研究。
This study examined the prognostic significance of microtubule-associated protein light chain 3B (LC3B) expression in oropharyngeal and oral cavity squamous cell carcinoma (SCC). The prognostic significance of LC3B expression in relation to human papillomavirus (HPV) status in oropharyngeal SCC was also examined. Tissue microarrays (TMAs) were constructed from formalin-fixed, paraffin-embedded oropharyngeal (n = 47) and oral cavity (n = 95) SCC tissue blocks from patients with long-term recurrence and overall survival data (median = 47 months). LC3B expression on tumour was assessed by immunohistochemistry and evaluated for associations with clinicopathological variables. LC3B expression was stratified into high and low expression cohorts using ROC curves with Manhattan distance minimisation, followed by Kaplan–Meier and multivariable survival analyses. Interaction terms between HPV status and LC3B expression in oropharyngeal SCC patients were also examined by joint-effects and stratified analyses. Kaplan–Meier survival and univariate analyses revealed that high LC3B expression was correlated with poor overall survival in oropharyngeal SCC patients (p = 0.007 and HR = 3.18, 95% CI 1.31–7.71, p = 0.01 respectively). High LC3B expression was also an independent prognostic factor for poor overall survival in oropharyngeal SCC patients (HR = 4.02, 95% CI 1.38–11.47, p = 0.011). In contrast, in oral cavity SCC, only disease-free survival remained statistically significant after univariate analysis (HR = 2.36, 95% CI 1.19–4.67, p = 0.014), although Kaplan-Meier survival analysis showed that high LC3B expression correlated with poor overall and disease-free survival (p = 0.046 and 0.011 respectively). Furthermore, oropharyngeal SCC patients with HPV-negative/high LC3B expression were correlated with poor overall survival in both joint-effects and stratified presentations (p = 0.024 and 0.032 respectively). High LC3B expression correlates with poor prognosis in oropharyngeal and oral cavity SCC, which highlights the importance of autophagy in these malignancies. High LC3B expression appears to be an independent prognostic marker for oropharyngeal SCC but not for oral cavity SCC patients. The difference in the prognostic significance of LC3B between oropharyngeal and oral cavity SCCs further supports the biological differences between these malignancies. The possibility that oropharyngeal SCC patients with negative HPV status and high LC3B expression were at particular risk of a poor outcome warrants further investigation in prospective studies with larger numbers.
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通讯作者：
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