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Cancers
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New Insights into Clinical and Translational Research in Nasopharyngeal Carcinoma
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New Insights into Clinical and Translational Research in Nasopharyngeal Carcinoma

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Clinical Research of Cancer".

Deadline for manuscript submissions: closed (10 November 2023) | Viewed by 18600

Special Issue Editors

Prof. Dr. Brigette Buig Yue Ma

E-Mail Website
Guest Editor
State Key Laboratory of Translational Oncology, Sir YK Pao Centre for Cancer, Phase 1 Clinical Trial Centre, Department of Clinical Oncology, The Chinese University of Hong Kong, Hong Kong SAR, China
Interests: head and neck cancer; colorectal cancer; phase 1 developmental therapeutics
Dr. Chi Man Tsang

E-Mail Website
Guest Editor
Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong SAR, China
Interests: nasopharyngeal carcinoma; Epstein–Barr virus; translational research
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Nasopharyngeal carcinoma (NPC) is endemic to certain regions in Asia/North Africa, and killed more than 80,000 people worldwide in 2020 (GLOBOCAN). Clinical and translational research spanning the last two decades has resulted in major breakthroughs in the development of new circulating biomarkers, early detection, therapeutic targets, and treatment paradigms. Advances in molecular biology have significantly improved our understanding of the genomic, epigenomic, and immune landscape of NPC right down to the single-cell level. Randomized clinical trials on combined-modality treatments and immune checkpoint inhibitors have all contributed to improving the clinical outcomes of patients afflicted with this cancer.

Thanks to these multidisciplinary efforts of clinicians and basic scientists, we are indeed living in a ‘Golden Age’ of NPC research. To commemorate the achievements of our predecessors and contemporaries, we are launching this Special Issue of Cancers, titled ‘New Insights into Clinical and Translational Research in Nasopharyngeal Carcinoma’. We welcome a diverse range of topics covering the latest developments and future directions in the clinical and translational research on NPC. These may include original research (translational research, clinical trials, biomarker studies, screening, and early detection), commentaries, systematic reviews, and meta-analyses.

Your contribution is vital to our endeavor, and we look forward to working with you and your colleagues in this Special Issue.  

Prof. Dr. Brigette Buig Yue Ma
Dr. Chi Man Tsang
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • nasopharyngeal carcinoma
  • clinical trials
  • biomarkers
  • chemotherapy
  • radiotherapy
  • immunotherapy
  • vaccines

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Published Papers (7 papers)

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21 pages, 5846 KiB  
Article
A Proteomic Analysis of Nasopharyngeal Carcinoma in a Moroccan Subpopulation
by Ayman Reffai, Michelle Hori, Ravali Adusumilli, Abel Bermudez, Abdelilah Bouzoubaa, Sharon Pitteri, Mohcine Bennani Mechita and Parag Mallick
Cancers 2024, 16(19), 3282; https://doi.org/10.3390/cancers16193282 - 26 Sep 2024
Viewed by 839
Abstract
Background: Nasopharyngeal carcinoma (NPC) is a distinct cancer of the head and neck that is highly prevalent in Southeast Asia and North Africa. Though an extensive analysis of environmental and genetic contributors has been performed, very little is known about the proteome of [...] Read more.
Background: Nasopharyngeal carcinoma (NPC) is a distinct cancer of the head and neck that is highly prevalent in Southeast Asia and North Africa. Though an extensive analysis of environmental and genetic contributors has been performed, very little is known about the proteome of this disease. A proteomic analysis of formalin-fixed paraffin-embedded (FFPE) tissues can provide valuable information on protein expression and molecular patterns for both increasing our understanding of the disease and for biomarker discovery. To date, very few NPC proteomic studies have been performed, and none focused on patients from Morocco and North Africa. Methods: Label-free Liquid Chromatography–Tandem Mass Spectrometry (LC-MS/MS) was used to perform a proteomic analysis of FFPE tissue samples from a cohort of 41 NPC tumor samples of Morocco and North Africa origins. The LC-MS/MS data from this cohort were analyzed alongside 21 healthy controls using MaxQuant 2.4.2.0. A differential expression analysis was performed using the MSstats package in R. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional annotations were carried out using the DAVID bioinformatic tool. Results: 3341 proteins were identified across our NPC cases, revealing three main clusters and five DEPs with prognostic significance. The sex disparity of NPC was investigated from a proteomic perspective in which 59 DEPs were found between males and females, with significantly enriched terms associated with the immune response and gene expression. Furthermore, 26 DEPs were observed between patients with early and advanced stages of NPC with a significant cluster related to the immune response, implicating up-regulated DEPs such as IGHA, IGKC, and VAT1. Across both datasets, 6532 proteins were quantified between NPC patients and healthy controls. Among them, 1507 differentially expressed proteins (DEPs) were observed. GO and KEGG pathway analyses showed enriched terms of DEPs related to increased cellular activity, cell proliferation, and survival. PI3K and MAPK proteins as well as RAC1 BCL2 and PPIA were found to be overexpressed between cancer tissues and healthy controls. EBV infection was also one of the enriched pathways implicating its latent genes like LMP1 and LMP2 that activate several proteins and signaling pathways including NF-Kappa B, MAPK, and JAK-STAT pathways. Conclusion: Our findings unveil the proteomic landscape of NPC for the first time in the Moroccan population. These studies additionally may provide a foundation for identifying potential biomarkers. Further research is still needed to help develop tools for the early diagnosis and treatment of NPC in Moroccan and North African populations. Full article
(This article belongs to the Special Issue New Insights into Clinical and Translational Research in Nasopharyngeal Carcinoma)
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17 pages, 5186 KiB  
Article
THY1 (CD90) Maintains the Adherens Junctions in Nasopharyngeal Carcinoma via Inhibition of SRC Activation
by Luo Chen, Wai Yin Chau, Hei Tung Yuen, Xiao Han Liu, Robert Zhong Qi, Maria Li Lung and Hong Lok Lung
Cancers 2023, 15(7), 2189; https://doi.org/10.3390/cancers15072189 - 6 Apr 2023
Cited by 1 | Viewed by 2412
Abstract
We had previously shown that THY1 (CD90) is a tumor suppressor in nasopharyngeal carcinoma (NPC) and that its down-regulation and loss of expression are associated with tumor metastasis, yet the mechanism leading to such effects remains unknown. In this study we show that [...] Read more.
We had previously shown that THY1 (CD90) is a tumor suppressor in nasopharyngeal carcinoma (NPC) and that its down-regulation and loss of expression are associated with tumor metastasis, yet the mechanism leading to such effects remains unknown. In this study we show that tumor invasion could be suppressed by THY1 via adherens junction formation in a few NPC cell lines, and knockdown of THY1 would disrupt this cell-cell adhesion phenotype. Mechanistically, the activity of the SRC family kinase (SFK) member, SRC, and canonical Wnt signaling were dramatically reduced when THY1 was constitutively expressed. Previous studies by others have found that high levels of SRC activity in NPCs are associated with EMT and a poor prognosis. We hypothesized that THY1 can suppress tumor invasion in NPC via inhibition of SRC. By gene silencing of SRC, we found that the in vitro NPC cell invasion was significantly reduced and adherens junctions were restored. Through proteomic analysis, we identified that platelet-derived growth factor receptor β (PDGF-Rβ) and protein tyrosine phosphatase nonreceptor type 22 (PTPN22) are novel and potential binding partners of THY1, which were subsequently verified by co-immunoprecipitation (co-IP) analysis. The ligand of PDGF-Rβ (PDGF-BB) could highly induce SRC activation and NPC cell invasion, which could be almost completely suppressed by THY1 expression. On the other hand, the PTPN22 siRNA could enhance both the SRC activities and the cell invasion and could also disrupt the adherens junctions in the THY1-expressing NPC cells; the original THY1-induced phenotypes were reverted when the PTPN22 expression was reduced. Together, our results identified that PTPN22 is essential for THY1 to suppress cell invasion and SRC activity, maintain tight adherens junctions, and prevent NPC metastasis. These results suggested that PDGF-Rβ and SRC can be used as drug targets for suppressing NPC metastasis. Indeed, our in vivo assay using the SRC inhibitor KX2-391, clearly showed that inhibition of SRC signaling can prevent the metastasis of NPC, indicating that targeting SRC can be a promising approach to control the NPC progression. Full article
(This article belongs to the Special Issue New Insights into Clinical and Translational Research in Nasopharyngeal Carcinoma)
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17 pages, 7032 KiB  
Article
Frequency of Peripheral CD8+ T Cells Expressing Chemo-Attractant Receptors CCR1, 4 and 5 Increases in NPC Patients with EBV Clearance upon Radiotherapy
by Shweta Mahajan, Hayri E. Balcioglu, Astrid Oostvogels, Willem A. Dik, K. C. Allen Chan, Kwok-Wai Lo, Edwin P. Hui, Anna Tsang, Joanna Tong, Wai Kei Jacky Lam, Kenneth Wong, Anthony T. C. Chan, Brigette B. Y. Ma and Reno Debets
Cancers 2023, 15(6), 1887; https://doi.org/10.3390/cancers15061887 - 21 Mar 2023
Viewed by 2151
Abstract
Radiotherapy (RT) is the standard-of-care for Epstein–Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC), where the post-RT clearance of plasma EBV DNA is prognostic. Currently, it is not known whether the post-RT clearance of plasma EBV DNA is related to the presence of circulating T-cell [...] Read more.
Radiotherapy (RT) is the standard-of-care for Epstein–Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC), where the post-RT clearance of plasma EBV DNA is prognostic. Currently, it is not known whether the post-RT clearance of plasma EBV DNA is related to the presence of circulating T-cell subsets. Blood samples from NPC patients were used to assess the frequency of T-cell subsets relating to differentiation, co-signaling and chemotaxis. Patients with undetectable versus detectable plasma EBV DNA levels post-RT were categorized as clearers vs. non-clearers. Clearers had a lower frequency of PD1+CD8+ T cells as well as CXCR3+CD8+ T cells during RT compared to non-clearers. Clearers exclusively showed a temporal increase in chemo-attractant receptors CCR1, 4 and/or 5, expressing CD8+ T cells upon RT. The increase in CCR-expressing CD8+ T cells was accompanied by a drop in naïve CD8+ T cells and an increase in OX40+CD8+ T cells. Upon stratifying these patients based on clinical outcome, the dynamics of CCR-expressing CD8+ T cells were in concordance with the non-recurrence of NPC. In a second cohort, non-recurrence associated with higher quantities of circulating CCL14 and CCL15. Collectively, our findings relate plasma EBV DNA clearance post-RT to T-cell chemotaxis, which requires validation in larger cohorts. Full article
(This article belongs to the Special Issue New Insights into Clinical and Translational Research in Nasopharyngeal Carcinoma)
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16 pages, 4606 KiB  
Article
An Integrative Analysis of Nasopharyngeal Carcinoma Genomes Unraveled Unique Processes Driving a Viral-Positive Cancer
by Xiaodong Liu, Yanjin Li, Xiang Zhou, Sinan Zhu, Neslihan A. Kaya, Yun Shen Chan, Liang Ma, Miao Xu and Weiwei Zhai
Cancers 2023, 15(4), 1243; https://doi.org/10.3390/cancers15041243 - 15 Feb 2023
Viewed by 2558
Abstract
As one of few viral-positive cancers, nasopharyngeal carcinoma (NPC) is extremely rare across the world but very frequent in several regions of the world, including Southern China (known as the Cantonese cancer). Even though several genomic studies have been conducted for NPC, their [...] Read more.
As one of few viral-positive cancers, nasopharyngeal carcinoma (NPC) is extremely rare across the world but very frequent in several regions of the world, including Southern China (known as the Cantonese cancer). Even though several genomic studies have been conducted for NPC, their sample sizes are relatively small and systematic comparison with other cancer types has not been explored. In this study, we collected four-hundred-thirty-one samples from six previous studies and provided the first integrative analysis of NPC genomes. Combining several statistical methods for detecting driver genes, we identified 25 novel drivers for NPC, including ATG14 and NLRC5. Many of these novel drivers are enriched in several important pathways, such as autophagy and immunity. By comparing NPC with many other cancer types, we found NPC is a unique cancer type in which a high proportion of patients (45.2%) do not have any known driver mutations (termed as “missing driver events”) but have a preponderance of deletion events, including chromosome 3p deletion. Through signature analysis, we identified many known and novel signatures, including single-base signatures (n = 12), double-base signatures (n = 1), indel signatures (n = 9) and copy number signatures (n = 8). Many of these new signatures are involved in DNA repair and have unknown etiology and genome instability, implying an unprecedented dynamic mutational process possibly driven by complex interactions between viral and host genomes. By combining clinical, molecular and intra-tumor heterogeneity features, we constructed the first integrative survival model for NPC, providing a strong basis for patient prognosis and stratification. Taken together, we have performed one of the first integrative analyses of NPC genomes and brought unique genomic insights into tumorigenesis of a viral-driven cancer. Full article
(This article belongs to the Special Issue New Insights into Clinical and Translational Research in Nasopharyngeal Carcinoma)
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16 pages, 3156 KiB  
Article
Radiomics for Discrimination between Early-Stage Nasopharyngeal Carcinoma and Benign Hyperplasia with Stable Feature Selection on MRI
by Lun M. Wong, Qi Yong H. Ai, Rongli Zhang, Frankie Mo and Ann D. King
Cancers 2022, 14(14), 3433; https://doi.org/10.3390/cancers14143433 - 14 Jul 2022
Cited by 8 | Viewed by 4239
Abstract
Discriminating early-stage nasopharyngeal carcinoma (NPC) from benign hyperplasia (BH) on MRI is a challenging but important task for the early detection of NPC in screening programs. Radiomics models have the potential to meet this challenge, but instability in the feature selection step may [...] Read more.
Discriminating early-stage nasopharyngeal carcinoma (NPC) from benign hyperplasia (BH) on MRI is a challenging but important task for the early detection of NPC in screening programs. Radiomics models have the potential to meet this challenge, but instability in the feature selection step may reduce their reliability. Therefore, in this study, we aim to discriminate between early-stage T1 NPC and BH on MRI using radiomics and propose a method to improve the stability of the feature selection step in the radiomics pipeline. A radiomics model was trained using data from 442 patients (221 early-stage T1 NPC and 221 with BH) scanned at 3T and tested on 213 patients (99 early-stage T1 NPC and 114 BH) scanned at 1.5T. To verify the improvement in feature selection stability, we compared our proposed ensemble technique, which uses a combination of bagging and boosting (BB-RENT), with the well-established elastic net. The proposed radiomics model achieved an area under the curve of 0.85 (95% confidence interval (CI): 0.82–0.89) and 0.80 (95% CI: 0.74–0.86) in discriminating NPC and BH in the 3T training and 1.5T testing cohort, respectively, using 17 features selected from a pool of 422 features by the proposed feature selection technique. BB-RENT showed a better feature selection stability compared to the elastic net (Jaccard index = 0.39 ± 0.14 and 0.24 ± 0.06, respectively; p < 0.001). Full article
(This article belongs to the Special Issue New Insights into Clinical and Translational Research in Nasopharyngeal Carcinoma)
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Review

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20 pages, 984 KiB  
Review
Optimizing Hearing Outcomes in Nasopharyngeal Cancer Survivors in the Era of Modern Radiotherapy and Systemic Therapy
by Jason C. S. Ho, Brigette B. Y. Ma and James C. H. Chow
Cancers 2024, 16(18), 3237; https://doi.org/10.3390/cancers16183237 - 23 Sep 2024
Viewed by 990
Abstract
Intensity-modulated radiation therapy (IMRT) improves disease control and reduces treatment-related toxicity in patients with localized nasopharyngeal carcinoma (NPC). However, due to the proximity of the auditory apparatus to the treatment volume and the frequent incorporation of cisplatin-based chemotherapy, treatment-related sensorineural hearing loss (SNHL) [...] Read more.
Intensity-modulated radiation therapy (IMRT) improves disease control and reduces treatment-related toxicity in patients with localized nasopharyngeal carcinoma (NPC). However, due to the proximity of the auditory apparatus to the treatment volume and the frequent incorporation of cisplatin-based chemotherapy, treatment-related sensorineural hearing loss (SNHL) remains a common debilitating complication among NPC survivors. The reported crude incidence of SNHL following IMRT for NPC varies widely at 1–46% due to differences in auditory assessment methods and thresholds, follow-up durations, chemotherapy usage, and patient compositions. International guidelines and radiation dosimetric studies have recommended constraining the cochlear mean dose to less than 44–50 Gy, but the risk of SNHL remains high despite adherence to these constraints. Potential strategies to improve hearing outcomes in NPC survivors include cautious de-escalation of radiotherapy dose and volume, individualization of cochlear constraints, optimization of radiotherapy planning techniques, and the use of substitutes or alternative schedules for cisplatin-based chemotherapy. The addition of immune checkpoint inhibitors to chemoradiotherapy did not impact ototoxicity. Prospective studies that employ both objective and patient-reported auditory outcomes are warranted to test the long-term benefits of various approaches. This article aims to provide a comprehensive review of the incidence and radiation dose–toxicity relationship of SNHL in NPC survivors and to summarize potential strategies to optimize hearing outcomes in relation to nuances in radiotherapy planning and the selection of systemic therapy. Full article
(This article belongs to the Special Issue New Insights into Clinical and Translational Research in Nasopharyngeal Carcinoma)
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15 pages, 314 KiB  
Review
Current Radiotherapy Considerations for Nasopharyngeal Carcinoma
by Wai Tong Ng, James C. H. Chow, Jonathan J. Beitler, June Corry, William Mendenhall, Anne W. M. Lee, K Thomas Robbins, Sandra Nuyts, Nabil F. Saba, Robert Smee, William A. Stokes, Primož Strojan and Alfio Ferlito
Cancers 2022, 14(23), 5773; https://doi.org/10.3390/cancers14235773 - 24 Nov 2022
Cited by 17 | Viewed by 4333
Abstract
Radiotherapy is the primary treatment modality for nasopharyngeal carcinoma (NPC). Successful curative treatment requires optimal radiotherapy planning and precise beam delivery that maximizes locoregional control while minimizing treatment-related side effects. In this article, we highlight considerations in target delineation, radiation dose, and the [...] Read more.
Radiotherapy is the primary treatment modality for nasopharyngeal carcinoma (NPC). Successful curative treatment requires optimal radiotherapy planning and precise beam delivery that maximizes locoregional control while minimizing treatment-related side effects. In this article, we highlight considerations in target delineation, radiation dose, and the adoption of technological advances with the aim of optimizing the benefits of radiotherapy in NPC patients. Full article
(This article belongs to the Special Issue New Insights into Clinical and Translational Research in Nasopharyngeal Carcinoma)
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