Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P.R. China.
Clinical Trials Centre, State Key Laboratory of Oncology in South China, Collaborative Innovation Centre of Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P.R. China.
Theranostics. 2020 Aug 1;10(21):9767-9778. doi: 10.7150/thno.47882. eCollection 2020.
Currently, for locoregionally advanced nasopharyngeal carcinoma (LA-NPC), there is no effective blood-based method to predict distant metastasis. We aimed to detect plasma protein profiles to identify biomarkers that could distinguish patients with NPC who are at high risk of posttreatment distant metastasis. A high-throughput antibody array was initially applied to detect 1000 proteins in pretreatment plasma from 16 matched LA-NPC patients with or without distant metastasis after radical treatment. Differentially expressed proteins were further examined using a low-throughput array to construct a plasma protein-based signature for distant metastasis (PSDM) in a cohort of 226 patients. Fifty circulating proteins were differentially expressed between metastatic and non-metastatic patients and 18 were proven to be strongly correlated with distant metastasis-free survival (DMFS) in NPC. A PSDM signature consisting of five proteins (SLAMF5, ESM-1, MMP-8, INSR, and Serpin A5) was established to assign patients with NPC into a high-risk group and a low-risk group. Patients in the high-risk group had shorter DMFS ( < 0.001), disease-free survival (DFS) ( < 0.001) and overall survival (OS) ( < 0.001). Moreover, the PSDM performed better than N stage and Epstein-Barr virus (EBV) DNA load at effectively identifying patients with NPC at high risk of metastasis. For patients in the high-risk group, induction chemotherapy significantly improved DMFS, DFS, and OS. The PSDM could be a useful liquid biopsy tool to effectively predict distant metastasis and the benefit of induction chemotherapy in patients with LA-NPC.
目前，对于局部晚期鼻咽癌（LA-NPC），尚无有效的基于血液的方法来预测远处转移。我们旨在检测血浆蛋白谱，以确定能够区分接受根治性治疗后有远处转移高风险的 NPC 患者的生物标志物。最初应用高通量抗体阵列检测 16 例经根治性治疗后有或无远处转移的 LA-NPC 患者治疗前血浆中的 1000 种蛋白。使用低通量阵列进一步检测差异表达蛋白，以构建 226 例患者远处转移（PSDM）的血浆蛋白签名。在转移性和非转移性患者之间有 50 种循环蛋白表达差异，其中 18 种蛋白被证明与 NPC 无远处转移生存（DMFS）密切相关。由五个蛋白（SLAMF5、ESM-1、MMP-8、INSR 和 Serpin A5）组成的 PSDM 签名用于将 NPC 患者分为高危组和低危组。高危组患者的 DMFS（<0.001）、无病生存（DFS）（<0.001）和总生存（OS）（<0.001）均较短。此外，PSDM 比 N 分期和 EBV DNA 载量更有效地识别具有 NPC 高转移风险的患者。对于高危组患者，诱导化疗显著改善了 DMFS、DFS 和 OS。PSDM 可能是一种有效的液体活检工具，可有效预测远处转移和 LA-NPC 患者诱导化疗的获益。
