Lee Sung-Wei, Yang Ching-Chieh, Lai Hong-Yue, Tsai Hsin-Hwa, Yeh Cheng-Fa, Kuo Yu-Hsuan, Kang Nai-Wen, Chen Tzu-Ju, Chang Shih-Lun
Department of Radiation Oncology, Chi Mei Medical Center, Liouying.
Department of Radiation Oncology, Chi Mei Medical Center, Tainan.
Clin Med Insights Oncol. 2022 Jul 22;16:11795549221113244. doi: 10.1177/11795549221113244. eCollection 2022.
Nasopharyngeal carcinoma (NPC) is a malignant tumor originating from the nasopharynx with high morbidity and mortality in Southeast Asia and south of China. Roundabout guidance receptor 1 (ROBO1) can regulate axonogenesis (axon-like protrusion), which may play an important role in migration. However, the roles of ROBO1 in NPC have not been clarified.
A comparative analysis employing the NPC transcriptome (GSE12452) and the axonogenesis-related genes (GO: 0050772) was performed. In total, 124 tissue blocks from patients primarily diagnosed as NPC (1993-2002) were examined using immunohistochemical staining. The connections between clinicopathological variables and protein immunoexpression were analyzed by Pearson's chi-square test. The Kaplan-Meier method with a log-rank test was employed to plot survival curves. Multivariate analysis was performed using the Cox proportional hazards model to identify independent prognostic biomarker.
According to transcriptome analysis, we found that ROBO1 is significantly highly expressed in NPC tissues compared with normal tissues. The immunohistochemistry (IHC) staining showed that high expression of ROBO1 was significantly related to primary tumor (T1T2 and T3T4) ( = .024), nodal metastasis status (N0N1 and N2N3) ( = .030), stage (I-II and III-IV) ( = .019), and histological grade (keratinizing, non-keratinizing, and undifferentiated) ( = .065). Importantly, NPC patients with high ROBO1 expression had poorer disease-specific survival (DSS) ( = .0001), distal metastasis-free survival (DMeFS) ( < .0001), and local recurrence-free survival (LRFS) ( = .0001) compared with NPC patients with low ROBO1 expression through the uni-/multivariate and the Kaplan-Meier survival analyses.
Our report indicates that ROBO1 might be a potential prognostic biomarker for NPC.
鼻咽癌（NPC）是一种起源于鼻咽部的恶性肿瘤，在东南亚和中国南方地区发病率和死亡率较高。环行蛋白导向受体1（ROBO1）可调节轴突发生（轴突样突起），这可能在迁移中起重要作用。然而，ROBO1在鼻咽癌中的作用尚未阐明。
采用鼻咽癌转录组（GSE12452）和轴突发生相关基因（GO: 0050772）进行比较分析。对1993 - 2002年初步诊断为鼻咽癌患者的124个组织块进行免疫组织化学染色检查。采用Pearson卡方检验分析临床病理变量与蛋白免疫表达之间的关系。采用Kaplan - Meier法和对数秩检验绘制生存曲线。使用Cox比例风险模型进行多变量分析，以确定独立的预后生物标志物。
根据转录组分析，我们发现与正常组织相比，ROBO1在鼻咽癌组织中显著高表达。免疫组织化学（IHC）染色显示，ROBO1的高表达与原发肿瘤（T1T2和T3T4）（P = 0.024）、淋巴结转移状态（N0N1和N2N3）（P = 0.030）、分期（I - II和III - IV）（P = 0.019）以及组织学分级（角化型、非角化型和未分化型）（P = 0.065）显著相关。重要的是，通过单因素/多因素分析和Kaplan - Meier生存分析，与低ROBO1表达的鼻咽癌患者相比，高ROBO1表达的鼻咽癌患者具有更差的疾病特异性生存（DSS）（P = 0.0001）、无远处转移生存（DMeFS）（P < 0.0001）和无局部复发生存（LRFS）（P = 0.0001）。
我们的报告表明，ROBO1可能是鼻咽癌潜在的预后生物标志物。
