Theranostics 2020; 10(21):9767-9778. doi:10.7150/thno.47882

Research Paper

Plasma protein-based signature predicts distant metastasis and induction chemotherapy benefit in Nasopharyngeal Carcinoma

Yelin Liang1*, Junyan Li1*, Qian Li1*, Linglong Tang1, Lei Chen1, Yanping Mao1, Qingmei He1, Xiaojing Yang1, Yuan Lei1, Xiaohong Hong1, Yin Zhao1, Shiwei He1, Ying Guo2, Yaqin Wang1, Panpan Zhang1, Na Liu1✉, Yingqin Li1✉, Jun Ma1✉

1. 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.
2. 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.
*These authors contributed equally to this work.

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Citation:
Liang Y, Li J, Li Q, Tang L, Chen L, Mao Y, He Q, Yang X, Lei Y, Hong X, Zhao Y, He S, Guo Y, Wang Y, Zhang P, Liu N, Li Y, Ma J. Plasma protein-based signature predicts distant metastasis and induction chemotherapy benefit in Nasopharyngeal Carcinoma. Theranostics 2020; 10(21):9767-9778. doi:10.7150/thno.47882. Available from http://www.thno.org/v10p9767.htm

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Abstract

Rationale: 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.

Methods: 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.

Results: 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 (P < 0.001), disease-free survival (DFS) (P < 0.001) and overall survival (OS) (P < 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.

Conclusions: 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.

Keywords: Protein-based signature, liquid biopsy, distant metastasis, Nasopharyngeal carcinoma, induction chemotherapy benefit