Molecular subtyping of nasopharyngeal carcinoma (NPC) and a microRNA-based prognostic model for distant metastasis

Zhao, Liang; Fong, Alvin H.; Liu, Na; Cho, William C. S.

doi:10.1186/s12929-018-0417-5

Cited by 41 publications

(30 citation statements)

References 51 publications

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“…Unfortunately, the anti-programmed cell death protein 1 (PD-1) therapies benefit only a subset of patients, while there is no strong evidence of the well-established ICI biomarkers in NPC [ 3 ]. Tumour gene expression profiles represent important resources to model the TME status and identify potential biomarkers [ 4 , 5 ]. In this study, we unraveled the TME heterogeneity based on gene expression profiles, and identified the distinct Active, Evaded and non-Immune Subtypes (A-IS, E-IS and non-IS) in NPC (Additional file 1 : Figure S1).…”

Section: Backgroudmentioning

confidence: 99%

Unraveling tumour microenvironment heterogeneity in nasopharyngeal carcinoma identifies biologically distinct immune subtypes predicting prognosis and immunotherapy responses

Chen¹,

Lv²,

Mao³

et al. 2021

Mol Cancer

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Currently, there is no strong evidence of the well-established biomarkers for immune checkpoint inhibitors (ICIs) in nasopharyngeal carcinoma (NPC). Here, we aimed to reveal the heterogeneity of tumour microenvironment (TME) through virtual microdissection of gene expression profiles. An immune-enriched subtype was identified in 38% (43/113) of patients, which was characterized by significant enrichment of immune cells or immune responses. The remaining patients were therefore classified as a non-Immune Subtype (non-IS), which exhibited highly proliferative features. Then we identified a tumour immune evasion state within the immune-enriched subtype (18/43, 42%), in which high expression of exclusion- and dysfunction-related signatures was observed. These subgroups were designated the Evaded and Active Immune Subtype (E-IS and A-IS), respectively. We further demonstrated that A-IS predicted favourable survival and improved ICI response as compared to E-IS and non-IS. In summary, this study introduces the novel immune subtypes and demonstrates their feasibility in tailoring immunotherapeutic strategies.

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Section: Backgroudmentioning

confidence: 99%

Unraveling tumour microenvironment heterogeneity in nasopharyngeal carcinoma identifies biologically distinct immune subtypes predicting prognosis and immunotherapy responses

Chen¹,

Lv²,

Mao³

et al. 2021

Mol Cancer

Self Cite

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“…Nasopharyngeal carcinoma (NPC) is one of the most common head and neck malignancies, which can be easily induced by environmental factors, genetic factors, and EB virus infection [1, 2]. NPCs have the pathological characteristics of high incidence, rapid deterioration, and poor prognosis and most NPC patients have developed to the middle- and late-stage by the time of diagnosis [3, 4]. Radiotherapy is dominated in the treatment of NPC due to the high sensitivity, but NPC cells are prone to distant metastasis and recurrence after treatment [5].…”

Section: Introductionmentioning

confidence: 99%

Circular RNA CDR1as sponges miR-7-5p to enhance E2F3 stability and promote the growth of nasopharyngeal carcinoma

et al. 2019

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Background Circular RNA (circRNA) CDR1as plays an important role in the occurrence and development of human tumors. The purpose of this study is to investigate the molecular mechanism of circRNA CDR1as in the development of nasopharyngeal carcinoma (NPC). Methods The mRNA expressions of circRNA CDR1as, miR-7-5p, and E2F3 were detected by qRT-PCR. The effects of circRNA CDR1as, miR-7-5p, and E2F3 on NPC cells were investigated using cell counting kit-8 (CCK8) method, colony formation assay, and representative metabolite assay. The molecular mechanism of circRNA CDR1 in NPC was studied by bioinformatics and luciferase reporter assay. In addition, the biological activity of circRNA CDR1as was also investigated in NPC xenograft tumor mice model. Results The results showed that the circRNA CDR1as expression was significantly up-regulated in NPC tissues by comparison with non-tumor NPE tissues (p < 0.01), suggesting that circRNA CDR1as was associated with poor prognosis in NPC patients. Moreover, circRNA CDR1as could up-regulate E2F3 expression by binding miR-7-5p, and promote the growth and glucose metabolism of NPC cells. Meanwhile, circRNA CDR1as could promote NPC progression through the negative regulation of miR-7-5p in the xenograft tumor model. Conclusion CircRNA CDR1as promoted the occurrence and development of NPCs by successively up-regulating the expression of miR-7-5p and E2F3, suggesting CircRNA CDR1as as a potential target for the treatment of NPC patients. Trial registration The study was approved by the cancer center’s institutional research ethics committee on Oct 18, 2008 (2008GZ2847462)

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“…As an effective and commonly used cancer treatment and the standard therapeutic intervention for various malignant tumors, IR causes DNA damage and destroys cancer cells to achieve its therapeutic effects [25]. Despite the high radiosensitivity of bulk cells, the existence of radioresistant cells in NPC tissue, however, lead to NPC recurrence and metastasis after radiation [26,27]. In this study, we found that NPC cells with lower expression of miR-34c displayed less sensitivity to irradiation, which contribute to the radioresistance of NPC in clinic.…”

Section: Discussionmentioning

confidence: 99%

Exosomes overexpressing miR-34c inhibit malignant behavior and reverse the radioresistance of nasopharyngeal carcinoma

et al. 2020

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Background: Malignant behavior and radioresistance, which severely limits the efficacy of radiation therapy (RT) in nasopharyngeal carcinoma (NPC), are associated with tumor progression and poor prognosis. Mesenchymal stem cells (MSCs) are used as a therapeutic tool in a variety of tumors. The aim of this study was to reveal the effect of tumor suppressor microRNA-34c-5p (miR-34c) on NPC development and radioresistance, as well as to confirm that exosomes derived from MSCs overexpressing miR-34c restore the sensitivity to radiotherapy in NPCs. Methods: Potentially active microRNAs were screened by cell sequencing, Gene Expression Omnibus (GEO) database analysis, and analysis of clinical serum samples from 70 patients. The expression of genes and proteins was detected by Western blotting, quantitative reverse transcription PCR (qRT-PCR), and immunohistochemistry (IHC). Proliferation, apoptosis, invasion, migration and radioresistance of NPC were detected. Luciferase reporter assays were used to verify the interactions of microRNAs with their downstream targets. MSCs exosomes were isolated by ultrafiltration and verified by electron microscopy and nanoparticle tracking technology. Results: The expression of miR-34c was associated with the occurrence and radiation resistance of NPC. In vitro and in vivo experiments indicated that overexpression of miR-34c inhibit malignant behavior such as invasion, migration, proliferation and epithelial-mesenchymal transition (EMT) in NPCs by targeting β-Catenin. In addition, we found alleviated radioresistance upon miR-34c overexpression or β-catenin knockdown in NPCs. Exosomes derived from miR-34c-transfected MSCs attenuated NPC invasion, migration, proliferation and EMT. Moreover, miR-34c-overexpressing exosomes drastically increased radiation-induced apoptosis in NPC cells. Conclusion: miR-34c is a tumor suppressor miR in NPC, which inhibits malignant behavior as well as radioresistance of tumor. Therefore, exogenous delivery of miR-34c to NPCs via MSC exosomes inhibits tumor progression and increases the efficiency of RT. Combination IR with miR-34c-overexpressing exosomes may be effective treatment for radioresistant NPCs.

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Molecular subtyping of nasopharyngeal carcinoma (NPC) and a microRNA-based prognostic model for distant metastasis

Cited by 41 publications

References 51 publications

Unraveling tumour microenvironment heterogeneity in nasopharyngeal carcinoma identifies biologically distinct immune subtypes predicting prognosis and immunotherapy responses

Unraveling tumour microenvironment heterogeneity in nasopharyngeal carcinoma identifies biologically distinct immune subtypes predicting prognosis and immunotherapy responses

Circular RNA CDR1as sponges miR-7-5p to enhance E2F3 stability and promote the growth of nasopharyngeal carcinoma

Exosomes overexpressing miR-34c inhibit malignant behavior and reverse the radioresistance of nasopharyngeal carcinoma

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