Abstract
We hypothesized that genetic variants in signaling pathways identified by next generation sequencing (NGS) are novel prognostic biomarkers for nasopharyngeal carcinoma. The purpose of this study was to evaluate gene variants in Adherens junction, PI3K-Akt, AMPK, Wnt and mTOR signaling pathway genes in patients with nasopharyngeal carcinoma (NPC) to predict treatment response and survival. A total of 32 NPC patients were enrolled from February 2018 to November 2018. Eligible patients were aged 33-66 years with histologically proven WHO Ⅱ-Ⅲ, stage Ⅱ-ⅣB (AJCC 7th) NPC. All patients received induction chemotherapy followed by concurrent chemoradiotherapy. Paraffin-embedded endoscopically NPC samples by endoscopic biopsy were available for all patients. The custom next generation sequencing assay was used to detect exons of 288 genes, introns, promoters or fusion in the dot region of 38 genes and partial exons of 728 genes related to NPC. Alterations of genes encoding the components of Adherens junction, PI3K-Akt, AMPK, Wnt and mTOR signaling pathway were detected. The association between genetic variants in these signaling pathway genes and treatment response and survival of NPC patients were analyzed. Patients with genetic variants in PI3K-Akt (HR = 0.32, P = 0.023), AMPK (HR = 0.26, P = 0.033), and mTOR (HR = 0.21, P = 0.016) signaling pathway genes had significantly inferior complete response rates as compared to patients without such genetic variants. Presence of gene variants in PI3K-Akt (P = 0.045), AMPK (P = 0.005) and mTOR signaling pathway (P = 0.001) were associated with significantly inferior 1-year regional failure-free survival (RFFS) and disease-free survival (DFS). No significant differences were observed in local failure-free survival (LFFS), distant metastasis-free survival (DMFS), and overall survival (OS) in patients with or without genetic variants in all of these signaling pathways. Gene variants in PI3K-Akt, AMPK and mTOR signaling pathway were associated with significantly inferior treatment response and disease-free survival in NPC patients. Gene variants in these signaling pathways identified by NGS profiling are potential novel prognostic markers for NPC.
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