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Updated: Jul 4, 2025
Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
Identification of novel molecular subtypes to improve the classification framework of nasopharyngeal carcinoma
Wanzun Lin1,2,3, Xiaochuan Chen1,2, Zongwei Huang1,2
1Department of Radiation Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China.
Background:
Nasopharyngeal carcinoma (NPC) treatment is largely based on a 'one-drug-fits-all' strategy in patients with similar pathological characteristics. However, given its biological heterogeneity, patients at the same clinical stage or similar therapies exhibit significant clinical differences. Thus, novel molecular subgroups based on these characteristics may better therapeutic outcomes.
Methods:
Herein, 192 treatment-naïve NPC samples with corresponding clinicopathological information were obtained from Fujian Cancer Hospital between January 2015 and January 2018. The gene expression profiles of the samples were obtained by RNA sequencing. Molecular subtypes were identified by consensus clustering. External NPC cohorts were used as the validation sets.
Results:
Patients with NPC were classified into immune, metabolic, and proliferative molecular subtypes with distinct clinical features. Additionally, this classification was repeatable and predictable as validated by the external NPC cohorts. Metabolomics has shown that arachidonic acid metabolites were associated with NPC malignancy. We also identified several key genes in each subtype using a weighted correlation network analysis. Furthermore, a prognostic risk model based on these key genes was developed and was significantly associated with disease-free survival (hazard ratio, 1.11; 95% CI, 1.07-1.16; P < 0.0001), which was further validated by an external NPC cohort (hazard ratio, 7.71; 95% CI, 1.39-42.73; P < 0.0001). Moreover, the 1-, 3-, and 5-year areas under the curve were 0.84 (95% CI, 0.74-0.94), 0.81 (95% CI, 0.73-0.89), and 0.82 (95% CI, 0.73-0.90), respectively, demonstrating a high predictive value.
Conclusions:
Overall, we defined a novel classification of nasopharyngeal carcinoma (immune, metabolism, and proliferation subtypes). Among these subtypes, metabolism and proliferation subtypes were associated with advanced stage and poor prognosis of NPC patients, whereas the immune subtype was linked to early stage and favorable prognosis.
Insights
This study identifies three novel molecular subtypes of nasopharyngeal carcinoma (NPC): immune, metabolic, and proliferative. The immune subtype shows a favorable prognosis, while metabolic and proliferative subtypes indicate advanced disease and poor outcomes.
Area of Science:
- Oncology
- Molecular Biology
- Genomics
Background:
- Nasopharyngeal carcinoma (NPC) treatment often uses a one-size-fits-all approach despite biological heterogeneity.
- Significant clinical variations exist among patients with similar pathological characteristics or treatment stages.
- Novel molecular subgroups are needed for improved therapeutic outcomes in NPC.
Purpose of the Study:
- To classify nasopharyngeal carcinoma (NPC) into distinct molecular subtypes.
- To identify key genes and develop a prognostic model for NPC.
- To correlate molecular subtypes with clinical features and patient prognosis.
Main Methods:
- RNA sequencing was performed on 192 treatment-naïve NPC samples.
- Consensus clustering was used to identify molecular subtypes.
- External NPC cohorts were utilized for validation of the classification and prognostic model.
Main Results:
- NPC patients were classified into immune, metabolic, and proliferative molecular subtypes.
- Arachidonic acid metabolites were linked to NPC malignancy.
- A prognostic risk model based on key genes demonstrated significant predictive value for disease-free survival (HR=1.11, P<0.0001).
Conclusions:
- A novel classification of NPC into immune, metabolism, and proliferation subtypes was established.
- Metabolism and proliferation subtypes are associated with advanced stage and poor prognosis.
- The immune subtype is linked to early stage and favorable prognosis in NPC patients.
