Prognostic implications of a molecular classifier derived from whole‐exome sequencing in nasopharyngeal carcinoma

Abstract

The aim of this study was to use whole‐exome sequencing to derive a molecular classifier for nasopharyngeal carcinoma (NPC) and evaluate its clinical performance. We performed whole‐exome sequencing on 82 primary NPC tumors from Sun Yat‐sen University Cancer Center (Guangzhou cohort) to obtain somatic single‐nucleotide variants, indels, and copy number variants. A novel molecular classifier was then developed and validated in another NPC cohort (Hong Kong cohort, n = 99). Survival analysis was estimated by the Kaplan‐Meier method and compared using the log‐rank test. Cox proportional hazards model was adopted for univariate and multivariate analyses. We identified three prominent NPC genetic subtypes: RAS/PI3K/AKT (based on RAS, AKT1, and PIK3CA mutations), cell‐cycle (based on CDKN2A/CDKN2B deletions, and CDKN1B and CCND1 amplifications), and unclassified (based on dominant mutations in epigenetic regulators, such as KMT2C/2D, or the Notch signaling pathway, such as NOTCH1/2). These subtypes differed in survival analysis, with good, intermediate, and poor progression‐free survival in the unclassified, cell‐cycle, and RAS/PI3K/AKT subgroups, respectively, among the Guangzhou, Hong Kong, and combined cohorts (n = 82, P = 0.0342; n = 99, P = 0.0372; and n = 181, P = 0.0023; log‐rank test). We have uncovered genetic subtypes of NPC with distinct mutations and/or copy number changes, reflecting discrete paths of NPC tumorigenesis and providing a roadmap for developing new prognostic biomarkers and targeted therapies.

Long Noncoding RNAs and Messenger RNAs Expression Profiles Potentially Regulated by ZBTB7A in Nasopharyngeal Carcinoma

“…Although SLC2A1, CDKN2B, and ISG15 are closely connected with NPC progression in other studies [31, 84, 85], our results do not show the positive results. The quantity of 20 chronic rhinitis and 60 NPC tissues is limited.…”

Efficacy, Safety, and Correlative Biomarkers of Toripalimab in Previously Treated Recurrent or Metastatic Nasopharyngeal Carcinoma: A Phase II Clinical Trial (POLARIS-02)

“…The frequently altered genes were consistent with previous reports. 36 , 37 Patients with genomic amplification in 11q13 region had no response and those with ETV6 genomic alterations had an ORR of 5.3%, indicating potential resistance mechanisms to immunotherapy. Genomic amplification in 11q13 region was previously reported to associate with poor response to toripalimab in melanoma 14 and esophageal squamous cell carcinoma.…”

Multiregional Sequencing of IDH-WT Glioblastoma Reveals High Genetic Heterogeneity and a Dynamic Evolutionary History

“…Specifically, EP300 and NCOR2 expression levels were correlated with survival and therapeutic response in GB [ 56 ]. In cancer, EP300 has been previously reported to target both mutations and structural alterations [ 57 ], which could be an important contributor to malignant transformation [ 58 , 59 , 60 ]. Growing evidence has demonstrated the role of Hippo signaling in cancer biology, and its alteration has been closely linked to tumorigenesis in many different cancers, also playing a key role in glioma development, including cell proliferation, apoptosis, and invasion [ 61 , 62 ].…”