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Abstract
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.
Highlights
Nasopharyngeal carcinoma (NPC) is an Epstein–Barr (EB) virus-associated epithelial malignancy exhibiting unusual ethnic and geographical distributions [1,2]
Some patients do not benefit from radiotherapy due to radioresistance caused by local recurrence and distant metastasis [7]
We identified 874 proteins, 20 of which were differentially expressed in radioresistant and radiosensitive NPC patients
Summary
Nasopharyngeal carcinoma (NPC) is an Epstein–Barr (EB) virus-associated epithelial malignancy exhibiting unusual ethnic and geographical distributions [1,2]. Some patients do not benefit from radiotherapy due to radioresistance caused by local recurrence and distant metastasis [7]. The molecular mechanism of radioresistance remains unclear; NPC is caused by many different factors, and few serum biomarkers predictive of radioresistance are known [13]. Protein overexpression led by related gene abnormality in serum cannot only reflect the degree of malignancy and lead to dynamic changes of protein expression after the excision of primary lesion and radiotherapy, indicating that abnormal expression of certain proteins was associated with NPC treatment and prognosis [17]. We analyzed the serum proteins of NPC patients who were either radiosensitive or radioresistant to build a diagnostic panel of prognosis after radiotherapy
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