Radiotherapy is the primary treatment option for nasopharyngeal carcinoma (NPC). Local recurrence and metastasis caused by radioresistance become a bottleneck of curative effect for patients with NPC. Currently, serum predictive biomarkers of radioresistance are scare. We enrolled NPC patients, who underwent radiotherapy in the Department of Oncology, Xiangya Hospital, Central Southern University, and analyzed the serum proteins profiles in NPC patients using with quantitative label-free proteomics using ultra-definition MS. Patients were divided into those who were radioresistant and radiosensitive by the overall reduction (≤50% or >50%, respectively) in tumor extent. The MS/MS spectrum database search identified 911 proteins and 809 proteins are quantitatable. Eight proteins significantly up-regulated and 12 serum proteins were significantly down-regulated in the radioresistance group compared with radiosensitivity group (P<0.05). Finally, five proteins entered the optimal models, including secreted protein acidic and cysteine rich (SPARC) (P=0.032), serpin family D member 1S (ERPIND1) (P=0.040), complement C4B (C4B) (P=0.017), peptidylprolyl Isomerase B (PPIB) (P=0.042), and family with sequence similarity 173 member A (FAM173A) (P=0.017). In all patient, the area under the curves (AUC) for SPARC, SERPIND, C4B, PPIB, and FAM173A were 0.716 (95% CI: 0.574-0.881), 0.697 (95% CI: 0.837-0.858), 0.686 (95% CI: 0.522-0.850), 0.668 (95% CI: 0.502-0.834) and 0.657 (95% CI: 0.512-0.825), respectively. The AUC of five selected proteins was 0.968 (95% CI: 0.918-1.000) with the sensitivity of 0.941 and the specificity of 0.926. Our result indicated that a panel including five serum protein (SPARC SERPIND1 C4B PPIB FAM173A) based on serum proteomics provided a high discrimination ability for radiotherapy effects in NPC patients. Studies with larger sample size and longer follow-up outcome are required.

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