Molecular landscape and subtype-specific therapeutic response of nasopharyngeal carcinoma revealed by integrative pharmacogenomics

Abstract

Nasopharyngeal carcinoma (NPC) is a malignant head and neck cancer type with high morbidity in Southeast Asia, however the pathogenic mechanism of this disease is poorly understood. Using integrative pharmacogenomics, we find that NPC subtypes maintain distinct molecular features, drug responsiveness, and graded radiation sensitivity. The epithelial carcinoma (EC) subtype is characterized by activations of microtubule polymerization and defective mitotic spindle checkpoint related genes, whereas sarcomatoid carcinoma (SC) and mixed sarcomatoid-epithelial carcinoma (MSEC) subtypes exhibit enriched epithelial-mesenchymal transition (EMT) and invasion promoting genes, which are well correlated with their morphological features. Furthermore, patient-derived organoid (PDO)-based drug test identifies potential subtype-specific treatment regimens, in that SC and MSEC subtypes are sensitive to microtubule inhibitors, whereas EC subtype is more responsive to EGFR inhibitors, which is synergistically enhanced by combining with radiotherapy. Through combinational chemoradiotherapy (CRT) screening, effective CRT regimens are also suggested for patients showing less sensitivity to radiation. Altogether, our study provides an example of applying integrative pharmacogenomics to establish a personalized precision oncology for NPC subtype-guided therapies.

Cytoplasmic Expression of LMP1 and its Nuclear Translocation in Nasopharyngeal Carcinoma Correlates with Epithelial-mesenchymal Transition

“…Of note, our previous report had already found that malignant spindle cells correlated closely with EMT, and should be the more aggressive subtype in NPC (Luo et al 2012a). Interesting, Ding RB et al has recently also showed that these sarcomatoid cells exhibited enriched EMT and invasion promoting genes (Ding et al 2021). Taken together, our results imply that nuclear LMP1 may promote greatly the dynamic progression of NPC.…”

“…2012a). Interesting, Ding RB et al has recently also showed that these sarcomatoid cells exhibited enriched EMT and invasion promoting genes (Ding et al . 2021).…”

Alpha-fetoprotein–producing recurrent nasopharyngeal carcinoma: A case report

“…NPCs are histologically classified into the following four subtypes based on morphologic characteristics: epithelial carcinoma (EC), sarcomatoid carcinoma (SC), mixed sarcomatoid-epithelial carcinoma (MSEC), and squamous cell carcinoma (SCC). 12 , 13 Our case is EC subtype, most of the tumor regions are identified with round epithelial cells and vesicular nuclei phenotype appearance. Figure 2(a) and ( m ) represent histological view of the primary and recurrent tumors, which shows similar morphologic traits.…”

“…sarcomatoid-epithelial carcinoma (MSEC), and squamous cell carcinoma (SCC). 12,13 Our case is EC subtype, most of the tumor regions are identified with round epithelial cells and vesicular nuclei phenotype appearance. Figure 2(a) and (m) represent histological view of the primary and recurrent tumors, which shows similar morphologic traits.…”

Predicting Radioresistant Biomarkers in Nasopharyngeal Carcinoma Patients Via Protein-Protein Interaction Network Analysis

“…Nasopharyngeal carcinoma (NPC), developing in the nasopharynx, is endemic in Southeast Asia and recognized as a head and neck malignancy. 1 The World Health Organization (WHO) grouped NPC into keratinizing squamous cell carcinoma, non-keratinizing squamous carcinoma, and undifferentiated carcinoma subtypes. 2 Risk factors associated with NPC are genetics, Epstein-Barr Virus(EBV), dietary factors, and smoking.…”