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Molecular Research in Squamous Cell Cancer of the Head and Neck

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: closed (31 May 2023) | Viewed by 10025

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Prof. Dr. Paweł Golusiński

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1. Department of Otolaryngology and Maxillofacial Surgery, University of Zielona Gora, Zyty 26, 65-046 Zielona Góra, Poland
2. Department of Maxillofacial Surgery, Poznan University of Medical Sciences, 61-701 Poznan, Poland
Interests: HPV in head and neck cancer; molecular biomarkers; minimally invasive transoral surgery

Special Issue Information

Dear Colleagues,

Despite the advances in diagnostics and treatment, head and neck cancer has still relatively poor prognosis. The locoregional relapse and formation of metastases are main causes for the adverse outcome. In last decade it has become evident that the infection with HPV a causative factor for a subset of head and cancer is the one of the most important prognosticators in head and neck cancer and is generally associated with better prognosis. However even in this subgroup, some “high risk” and “low risk” tumors can be identified. Therefore there is a need for identification of reliable biomarkers which could potentially help to identify the subgroups of patients suitable for more personalized approach and use of the treatment algorithms associated with good oncological outcomes and low morbidity.

We encourage submission of both original research articles and topical reviews. Since our journal is focused on molecular sciences, and therefore, pure clinical research is not fitted with this Special Issue.

Prof. Dr. Paweł Golusiński
Guest Editor

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Keywords

head and neck cancer
HPV
biomarkers
prognostic factors
molecular diagnostics
tumor immunology

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Published Papers (4 papers)

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Research

18 pages, 2222 KiB

Open AccessArticle

Metabolomic Insight into Implications of Induction Chemotherapy Followed by Concomitant Chemoradiotherapy in Locally Advanced Head and Neck Cancer

by Łukasz Boguszewicz, Agata Bieleń, Mateusz Ciszek, Agnieszka Skorupa, Jolanta Mrochem-Kwarciak, Krzysztof Składowski and Maria Sokół

Int. J. Mol. Sci. 2024, 25(1), 188; https://doi.org/10.3390/ijms25010188 - 22 Dec 2023

Cited by 1 | Viewed by 1673

Abstract

The present study compares two groups of locally advanced patients with head and neck squamous cell carcinoma (LA-HNSCC) undergoing concurrent chemoradiotherapy (cCHRT), specifically those for whom it is a first-line treatment and those who have previously received induction chemotherapy (iCHT). The crucial question is whether iCHT is a serious burden during subsequent treatment for LA-HNSCC and how iCHT affects the tolerance to cCHRT. Of the 107 LA-HNSCC patients, 54 received cisplatin-based iCHT prior to cCHRT. The patients were clinically monitored at weekly intervals from the day before until the completion of the cCHRT. The 843 blood samples were collected and divided into two aliquots: for laboratory blood tests and for nuclear magnetic resonance (NMR) spectroscopy (a Bruker 400 MHz spectrometer). The NMR metabolites and the clinical parameters from the laboratory blood tests were analyzed using orthogonal partial least squares analysis (OPLS) and the Mann–Whitney U test (MWU). After iCHT, the patients begin cCHRT with significantly (MWU p-value < 0.05) elevated blood serum lipids, betaine, glycine, phosphocholine, and reticulocyte count, as well as significantly lowered NMR inflammatory markers, serine, hematocrit, neutrophile, monocyte, red blood cells, hemoglobin, and CRP. During cCHRT, a significant increase in albumin and psychological distress was observed, as well as a significant decrease in platelet, N-acetyl-cysteine, tyrosine, and phenylalanine, in patients who received iCHT. Importantly, all clinical symptoms (except the decreased platelets) and most metabolic alterations (except for betaine, serine, tyrosine, glucose, and phosphocholine) resolve until the completion of cCHRT. In conclusion, iCHT results in hematological toxicity, altered lipids, and one-carbon metabolism, as well as downregulated inflammation, as observed at the beginning and during cCHRT. However, these complications are temporary, and most of them resolve at the end of the treatment. This suggests that iCHT prior to cCHRT does not pose a significant burden and should be considered as a safe treatment option for LA-HNSCC. Full article

(This article belongs to the Special Issue Molecular Research in Squamous Cell Cancer of the Head and Neck)

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20 pages, 4190 KiB

Open AccessArticle

Tumor-Suppressive and Immunomodulating Activity of miR-30a-3p and miR-30e-3p in HNSCC Cells and Tumoroids

by Ombline Conrad, Mickaël Burgy, Sophie Foppolo, Aude Jehl, Alicia Thiéry, Sébastien Guihard, Romain Vauchelles, Alain C. Jung, Jana Mourtada, Christine Macabre, Sonia Ledrappier, Marie-Pierre Chenard, Mihaela-Alina Onea, Aurélien Danic, Thomas Dourlhes, Claire Thibault, Philippe Schultz, Monique Dontenwill and Sophie Martin

Int. J. Mol. Sci. 2023, 24(13), 11178; https://doi.org/10.3390/ijms241311178 - 6 Jul 2023

Cited by 6 | Viewed by 2535

Abstract

Head and neck squamous cell carcinomas (HNSCCs) are heterogeneous tumors, well known for their frequent relapsing nature. To counter recurrence, biomarkers for early diagnosis, prognosis, or treatment response prediction are urgently needed. miRNAs can profoundly impact normal physiology and enhance oncogenesis. Among all of the miRNAs, the miR-30 family is frequently downregulated in HNSCC. Here, we determined how levels of the 3p passenger strands of miR-30a and miR-30e affect tumor behavior and clarified their functional role in LA-HNSCC. In a retrospective study, levels of miR-30a-3p and miR-30e-3p were determined in 110 patients and correlated to overall survival, locoregional relapse, and distant metastasis. miR-30a/e-3p were expressed in HNSCC cell lines and HNSCC patient-derived tumoroids (PDTs) to investigate their effect on tumor cells and their microenvironment. Both miRNAs were found to have a prognosis value since low miR-30a/e-3p expression correlates to adverse prognosis and reduces overall survival. Low expression of miR-30a/e-3p is associated with a shorter time until locoregional relapse and a shorter time until metastasis, respectively. miR-30a/e-3p expression downregulates both TGF-βR1 and BMPR2 and attenuates the survival and motility of HNSCC. Results were confirmed in PDTs. Finally, secretomes of miR-30a/e-3p-transfected HNSCC activate M1-type macrophages, which exert stronger phagocytic activities toward tumor cells. miR-30a/e-3p expression can discriminate subgroups of LA-HNSCC patients with different prognosis, making them good candidates as prognostic biomarkers. Furthermore, by targeting members of the TGF-β family and generating an immune-permissive microenvironment, they may emerge as an alternative to anti-TGF-β drugs to use in combination with immune checkpoint inhibitors. Full article

(This article belongs to the Special Issue Molecular Research in Squamous Cell Cancer of the Head and Neck)

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23 pages, 4291 KiB

Open AccessArticle

Exploiting Vitamin D Receptor and Its Ligands to Target Squamous Cell Carcinomas of the Head and Neck

by Laura Koll, Désirée Gül, Manal I. Elnouaem, Hanaa Raslan, Omneya R. Ramadan, Shirley K. Knauer, Sebastian Strieth, Jan Hagemann, Roland H. Stauber and Aya Khamis

Int. J. Mol. Sci. 2023, 24(5), 4675; https://doi.org/10.3390/ijms24054675 - 28 Feb 2023

Cited by 13 | Viewed by 2959

Abstract

Vitamin D (VitD) and its receptor (VDR) have been intensively investigated in many cancers. As knowledge for head and neck cancer (HNC) is limited, we investigated the (pre)clinical and therapeutic relevance of the VDR/VitD-axis. We found that VDR was differentially expressed in HNC tumors, correlating to the patients’ clinical parameters. Poorly differentiated tumors showed high VDR and Ki67 expression, whereas the VDR and Ki67 levels decreased from moderate to well-differentiated tumors. The VitD serum levels were lowest in patients with poorly differentiated cancers (4.1 ± 0.5 ng/mL), increasing from moderate (7.3 ± 4.3 ng/mL) to well-differentiated (13.2 ± 3.4 ng/mL) tumors. Notably, females showed higher VitD insufficiency compared to males, correlating with poor differentiation of the tumor. To mechanistically uncover VDR/VitD’s pathophysiological relevance, we demonstrated that VitD induced VDR nuclear-translocation (VitD < 100 nM) in HNC cells. RNA sequencing and heat map analysis showed that various nuclear receptors were differentially expressed in cisplatin-resistant versus sensitive HNC cells including VDR and the VDR interaction partner retinoic acid receptor (RXR). However, RXR expression was not significantly correlated with the clinical parameters, and cotreatment with its ligand, retinoic acid, did not enhance the killing by cisplatin. Moreover, the Chou–Talalay algorithm uncovered that VitD/cisplatin combinations synergistically killed tumor cells (VitD < 100 nM) and also inhibited the PI3K/Akt/mTOR pathway. Importantly, these findings were confirmed in 3D-tumor-spheroid models mimicking the patients’ tumor microarchitecture. Here, VitD already affected the 3D-tumor-spheroid formation, which was not seen in the 2D-cultures. We conclude that novel VDR/VitD-targeted drug combinations and nuclear receptors should also be intensely explored for HNC. Gender-specific VDR/VitD-effects may be correlated to socioeconomic differences and need to be considered during VitD (supplementation)-therapies. Full article

(This article belongs to the Special Issue Molecular Research in Squamous Cell Cancer of the Head and Neck)

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12 pages, 1000 KiB

Open AccessArticle

Clinical Significance of Claudin Expression in Oral Squamous Cell Carcinoma

by Tatjana Zejc, Jörg Piontek, Jörg-Dieter Schulzke, Michael Fromm, Jürgen Ervens and Rita Rosenthal

Int. J. Mol. Sci. 2022, 23(19), 11234; https://doi.org/10.3390/ijms231911234 - 23 Sep 2022

Cited by 9 | Viewed by 2096

Abstract

A change in claudin expression has been demonstrated in various tumors. The present study specifically compares claudin expression in oral squamous cell carcinoma (OSCC) with healthy oral epithelium from the same individual and analyzes the association between claudin expression and the clinically relevant course parameters. Our study includes tissue samples and clinically relevant follow-up data from 60 patients with primary and untreated OSCC. The oral mucosa was analyzed via Western blot for the expression of claudin-1, -2, -3, -4, -5, and -7. Importantly, the tumor and healthy tissues were obtained pairwise from patients, allowing for intraindividual comparisons. Both the healthy and tumor epithelium from the oral cavity did not express the claudin-3 protein. The intraindividual comparison revealed that, in OSCC, claudin-2 expression was higher, and the expression of claudin-4, -5, and -7 was lower than in healthy epithelium. An association was found between increased claudin-2 expression and shorter relapse-free survival. In addition, the reduced expression of claudin-4 had a negative impact on relapse-free survival. Furthermore, associations between the reduced expression of claudin-7 and the stage of a tumor, or the presence of lymph node metastases, were found. Thus, the expression level of claudin-2, -4, and -7 appears to be predictive of the diagnosis and prognosis of OSCC. Full article

(This article belongs to the Special Issue Molecular Research in Squamous Cell Cancer of the Head and Neck)

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