Tang XR, et al. - The purpose of this research was to spot out a gene expression pattern for individual distant metastatic risk assessment in patients with locoregionally advanced nasopharyngeal carcinoma. Data demonstrated that distant metastasis gene signature for locoregionally advanced nasopharyngeal carcinoma (DMGN) was a reliable prognostic instrument for distant metastasis in the study cohort. It could aid in speculating which patients gained benefit from concurrent chemotherapy. As per the outcomes, this tool displayed the potential to guide therapeutic decisions for patients at different risk of distant metastasis.

Methods

• The scheme of this research was a multicentre, retrospective cohort study.
• The enrollment consisted of 937 patients with locoregionally advanced nasopharyngeal carcinoma from 3 Chinese hospitals: The Sun Yat-sen University Cancer Center (Guangzhou, China), the Affiliated Hospital of Guilin Medical University (Guilin, China), and the First People's Hospital of Foshan (Foshan, China).
• The mRNA gene expression between 24 paired locoregionally advanced nasopharyngeal carcinoma tumours was profiled with the aid of microarray analysis from patients at Sun Yat-sen University Cancer Center with or without distant metastasis after radical treatment.
• Using digital expression profiling, experts scrutinized the differentially expressed genes in a training cohort (Guangzhou training cohort; n=410) to build a gene classifier using a penalised regression model.
• The prognostic accuracy of this gene classifier was validated in an internal validation cohort (Guangzhou internal validation cohort, n=204) and two external independent cohorts (Guilin cohort, n=165; Foshan cohort, n=158).
• Distant metastasis-free survival served as the primary endpoint.
• Secondary endpoints included disease-free survival and overall survival.

Results

• A total of 137 differentially expressed genes were detected between metastatic and non-metastatic locoregionally advanced nasopharyngeal carcinoma tissues.
• Findings revealed a distant metastasis gene signature for locoregionally advanced nasopharyngeal carcinoma (DMGN) that consisted of 13 genes which classified patients into high-risk and low-risk groups in the training cohort.
• Shorter distant metastasis-free survival (hazard ratio [HR] 4·93, 95% CI 2·99-8·16; p < 0·0001), disease-free survival (HR 3·51, 2·43-5·07; p < 0·0001), and overall survival (HR 3·22, 2·18-4·76; p < 0·0001) were reported among subjects with high-risk scores in the training cohort vs patients with low-risk scores.
• In the internal and external cohorts, the prognostic accuracy of DMGN was validated.
• Concurrent chemotherapy led to an improvement in the distant metastasis-free survival among patients with low-risk scores in the combined training and internal cohorts, compared with those patients who did not receive concurrent chemotherapy (HR 0·40, 95% CI 0·19-0·83; p=0·011).
• On the other hand, candidates with high-risk scores did not benefit from concurrent chemotherapy (HR 1·03, 0·71-1·50; p=0·876), which was also validated in the two external cohorts combined.
• A nomogram based on the DMGN and other variables was formulated which speculated an individual's risk of distant metastasis, which was strengthened through the addition of Epstein-Barr virus DNA status.