Abstract
BackgroundTreatment protocols for nasopharyngeal carcinoma (NPC) developed in the past decade have significantly improved patient survival. In most NPC patients, however, the disease is diagnosed at late stages, and for some patients treatment response is less than optimal. This investigation has two aims: to identify a blood-based gene-expression signature that differentiates NPC from other medical conditions and from controls and to identify a biomarker signature that correlates with NPC treatment response.MethodsRNA was isolated from peripheral whole blood samples (2 x 10 ml) collected from NPC patients/controls (EDTA vacutainer). Gene expression patterns from 99 samples (66 NPC; 33 controls) were assessed using the Affymetrix array. We also collected expression data from 447 patients with other cancers (201 patients) and non-cancer conditions (246 patients). Multivariate logistic regression analysis was used to obtain biomarker signatures differentiating NPC samples from controls and other diseases. Differences were also analysed within a subset (n = 28) of a pre-intervention case cohort of patients whom we followed post-treatment.ResultsA blood-based gene expression signature composed of three genes — LDLRAP1, PHF20, and LUC7L3 — is able to differentiate NPC from various other diseases and from unaffected controls with significant accuracy (area under the receiver operating characteristic curve of over 0·90). By subdividing our NPC cohort according to the degree of patient response to treatment we have been able to identify a blood gene signature that may be able to guide the selection of treatment.ConclusionWe have identified a blood-based gene signature that accurately distinguished NPC patients from controls and from patients with other diseases. The genes in the signature, LDLRAP1, PHF20, and LUC7L3, are known to be involved in carcinoma of the head and neck, tumour-associated antigens, and/or cellular signalling. We have also identified blood-based biomarkers that are (potentially) able to predict those patients who are more likely to respond to treatment for NPC. These findings have significant clinical implications for optimizing NPC therapy.
Highlights
Treatment protocols for nasopharyngeal carcinoma (NPC) developed in the past decade have significantly improved patient survival
Of the 66 patients with NPC, there were more males than females (49 males, 17 females; see Table 1), a finding consistent with previous studies indicating that the incidence of NPC is higher in men than in women
Of the 234 probe sets, we found that the three selected most frequently and in the best combinations mapped to genes LDLRAP1, PHF20 (PHD finger protein 20) and
Summary
Treatment protocols for nasopharyngeal carcinoma (NPC) developed in the past decade have significantly improved patient survival. In most NPC patients, the disease is diagnosed at late stages, and for some patients treatment response is less than optimal. In parts of Africa and in Asia, NPC is much more common. The highest incidence worldwide occurs in southeast China; in Hong Kong for example, NPC affects approximately 20–30 per 100,000 men and 15–20 per 100,000 women [1]. The disease is more often diagnosed in men than in women, and tends to occur at an earlier age than do most cancers. In high-risk populations the risk of NPC increases slowly throughout the lifespan, with a peak incidence at 45–54 years. In moderate-risk groups, such as populations in North Africa, there is an additional peak in adolescence and youth (ages 10–20) [3]
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