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Oral Squamous Cell Carcinoma—Pathogenetic, Diagnostic and Therapeutic Perspectives

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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 (29 November 2023) | Viewed by 27384

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Special Issue Editors

Prof. Dr. Ana Caruntu

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Guest Editor

1. Department of Oral and Maxillofacial Surgery, Faculty of Dental Medicine, Titu Maiorescu University, 031593 Bucharest, Romania
2. Department of Oral and Maxillofacial Surgery, Carol Davila Central Military Emergency Hospital, 010825 Bucharest, Romania
Interests: tissue regeneration; healing; head and neck cancer; biomaterials; inflammation; biomarkers
Special Issues, Collections and Topics in MDPI journals

Prof. Dr. Shun-Fa Yang

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Guest Editor

1. Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan
2. Department of Medical Research, Chung Shan Medical University Hospital, Taichung 40201, Taiwan
Interests: eye diseases; polymorphism; cancer prevention; cancer biomarker; oral cancer; cancer metastasis; matrix metalloproteinase
Special Issues, Collections and Topics in MDPI journals

Dr. Julio Acero

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Guest Editor

1. Department of Oral and Maxillofacial Surgery, Hospital Ramon y Cajal, 28034 Madrid, Spain
2. Hospital Universitario Puerta de Hierro, 28222 Majadahonda, Spain
Interests: head and neck cancer; head and neck reconstruction; tissue engineering; microvascular surgery; stem cells; oral cancer; oral surgery; orbital surgery; midfacial surgery
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Oral Squamous Cell Carcinoma (OSCC), the most common form of head and neck cancer, remains one of the major challenges of modern medicine, despite all progressed made during the last decades in cancer control for other types of malignancies. Statistical data show that the incidence of OSCC is continuously rising, while the prognosis has not improved significantly, with important mortality rates, especially associated with advanced disease at the moment of diagnosis. Some aspects regarding the carcinogenesis process in OSCC have been elucidated. Today we know that lesions of OSCC imply multiple genetic alterations in combination with exposure to behaviour or environmental risk factors. However, the exact mechanisms leading to cancer development and, more importantly, the elements which influence the response to therapy are far from being unveiled. Several questions remain unanswered: Who will suffer from OSCC during their lifetime? or How to increase the response to therapy rate in OSCC patients?

This Special issue aims to gather the most recent research conducted in the complex domain of molecular mechanisms that impact carcinogenesis, response to therapy and prognosis in OSCC. Experimental studies, as well as clinical submissions with biomolecular experiments are within the scope of our Special issue and are welcomed for submission. All authors are invited to send their research related to the topic of our Special issue, both original and review articles, to be assessed and included in the peer review process of our journal.

Prof. Dr. Ana Caruntu
Prof. Dr. Shun-Fa Yang
Dr. Julio Acero
Guest Editors

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Keywords

oral squamous cell carcinoma
molecular biology
pathology
microbiome
biomarkers
genetic alterations
biological behavior
diagnostics and therapeutics
reconstructive therapy
chemoresistance
radioresistantce

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Published Papers (12 papers)

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Editorial

Jump to: Research, Review

3 pages, 178 KiB

Open AccessEditorial

New Insights for an Advanced Understanding of the Molecular Mechanisms in Oral Squamous Cell Carcinoma

by Ana Caruntu, Shun-Fa Yang and Julio Acero

Int. J. Mol. Sci. 2024, 25(13), 6964; https://doi.org/10.3390/ijms25136964 - 26 Jun 2024

Viewed by 1891

Abstract

Oral squamous cell carcinoma (OSCC), the most common type of head and neck cancer, remains a highly challenging cancer to treat, largely due to the late diagnosis in advanced stages of the disease, which occurs in more than half of cases [...] Full article

(This article belongs to the Special Issue Oral Squamous Cell Carcinoma—Pathogenetic, Diagnostic and Therapeutic Perspectives)

Research

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12 pages, 637 KiB

Open AccessArticle

The Interaction between CLSPN Gene Polymorphisms and Alcohol Consumption Contributes to Oral Cancer Progression

by Ming-Ju Hsieh, Yu-Sheng Lo, Hsin-Yu Ho, Chia-Chieh Lin, Yi-Ching Chuang and Mu-Kuan Chen

Int. J. Mol. Sci. 2024, 25(2), 1098; https://doi.org/10.3390/ijms25021098 - 16 Jan 2024

Cited by 2 | Viewed by 1285

Abstract

Most disease single nucleotide polymorphisms (SNPs) are regulatory and approximately half of heritability is occupied by the top 1% of genes, with the gene-level structure varying with the number of variants associated with the most common alleles. Cancer occurrence and progression are significantly affected by Claspin (CLSPN) gene polymorphism present in the population, which alters the expression, function, and regulation of the gene. CLSPN genotypes are associated with oral cancer, but the literature on this association is limited. As a result, the goal of this study is to investigate the correlation between CLSPN genotypes and oral cancers’ development. This study will explore the presence of four CLSPN SNPs including rs12058760, rs16822339, rs535638 and rs7520495 gene polymorphisms, and analyze the expression of these genes in 304 cancer-free controls and 402 oral squamous cell carcinoma (OSCC) cases. Attempts have been made to obtain insight into the role of CLSPN gene polymorphisms in oral cancer through the analysis of this study. We demonstrated that the OSCC risk of individuals with four CLSPN SNPs relative to the wild type did not differ significantly from that of the wild type when the polymorphisms are analyzed according to individual habits. We further studied the mechanism by which CLSPN polymorphisms affect the progression of clinicopathological features in OSCC patients. The results of the degree of cell differentiation showed that compared with patients of rs7520495 SNP carrying the CC genotype, the incidence of poor cell differentiation in patients carrying the CC + GG genotype was higher (AOR: 1.998-fold; 95% CI, 1.127–3.545; p = 0.018). In particular, patients with the G genotype of rs7520495 had increased poor cell differentiation compared with patients with the C genotype (AOR: 4.736-fold; 95% CI, 1.306–17.178; p = 0.018), especially in the drinking group. On the basis of our analysis of the Cancer Genome Atlas dataset, we found that higher CLSPN levels were associated with poorer cell differentiation in oral cancers. In this study, we provide the first evidence showing that CLSPN SNPs contribute to oral cancer. Whether or not rs7520495 can be used as a confirmatory factor in the future is uncertain, but it seems likely that it can be used as an important factor in predicting recurrence, response to treatment and medication toxicity to patients with oral cancer. Full article

(This article belongs to the Special Issue Oral Squamous Cell Carcinoma—Pathogenetic, Diagnostic and Therapeutic Perspectives)

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13 pages, 1492 KiB

Open AccessArticle

HLA-E and Its Soluble Form as Indicators of a Sex-Specific Immune Response in Patients with Oral Squamous Cell Carcinoma

by Anne Radermacher, Michael Fehrenz, Tamara Bellin, Carolina Claßen, Laura Möller, Ann-Kristin Struckmeier, Mathias Wagner, Philipp Wartenberg, Julius Moratin, Christian Freudlsperger, Kolja Freier and Dominik Horn

Int. J. Mol. Sci. 2023, 24(23), 16699; https://doi.org/10.3390/ijms242316699 - 24 Nov 2023

Viewed by 1230

Abstract

The human leukocyte antigene E (HLA-E) is associated with tumorigenesis in various cancers. Immunoncology along with sex-specific aspects in cancer therapy are now in scientific focus. Therefore, immunohistochemical HLA-E expression was retrospectively analysed in a cohort of oral squamous cell carcinomas (OSCC) after surgical therapy. Then, serum concentration of HLA-E (sHLA-E) was quantified in a prospective cohort by enzyme-linked immunosorbent assay. High HLA-E expression was associated with advanced UICC stage (Spearman’s correlation: p = 0.002) and worse survival (Cox-regression: progression-free survival: hazard ratio (HR) 3.129, confidence range (CI) 1.443–6.787, p = 0.004; overall survival: HR 2.328, CI 1.071–5.060, p = 0.033). The sHLA-E concentration was significantly higher in the control group than in tumor group (Mann–Whitney U-test (MW-U): p = 0.021). Within the tumor group, women showed significantly higher sHLA-E levels than men (MW-U: p = 0.049). A closer look at the tumor group and the control group showed that gender-specific differences exist: while no differences in sHLA-E concentration were detectable between female subjects of tumor group and control group (MW-U: p = 0.916), male subjects of tumor group had a significantly lower sHLA-E concentration compared to those of control group (MW-U: p = 0.001). In summary, our results provide evidence for sex-specific differences in immune responses in OSCC. This fact should be considered regarding future immunotherapy regimens. Full article

(This article belongs to the Special Issue Oral Squamous Cell Carcinoma—Pathogenetic, Diagnostic and Therapeutic Perspectives)

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20 pages, 1826 KiB

Open AccessArticle

Salivary Chemical Barrier Proteins in Oral Squamous Cell Carcinoma—Alterations in the Defense Mechanism of the Oral Cavity

by Gergő Kalló, Petra Magdolna Bertalan, Ildikó Márton, Csongor Kiss and Éva Csősz

Int. J. Mol. Sci. 2023, 24(17), 13657; https://doi.org/10.3390/ijms241713657 - 4 Sep 2023

Cited by 5 | Viewed by 2203

Abstract

Oral squamous cell carcinoma (OSCC) is one of the most frequent types of head and neck cancer. Despite the genetic and environmental risk factors, OSCC is also associated with microbial infections and/or dysbiosis. The secreted saliva serves as the chemical barrier of the oral cavity and, since OSCC can alter the protein composition of saliva, our aim was to analyze the effect of OSCC on the salivary chemical barrier proteins. Publicly available datasets regarding the analysis of salivary proteins from patients with OSCC and controls were collected and examined in order to identify differentially expressed chemical barrier proteins. Network analysis and gene ontology (GO) classification of the differentially expressed chemical barrier proteins were performed as well. One hundred and twenty-seven proteins showing different expression pattern between the OSCC and control groups were found. Protein–protein interaction networks of up- and down-regulated proteins were constructed and analyzed. The main hub proteins (IL-6, IL-1B, IL-8, TNF, APOA1, APOA2, APOB, APOC3, APOE, and HP) were identified and the enriched GO terms were examined. Our study highlighted the importance of the chemical barrier of saliva in the development of OSCC. Full article

(This article belongs to the Special Issue Oral Squamous Cell Carcinoma—Pathogenetic, Diagnostic and Therapeutic Perspectives)

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13 pages, 1392 KiB

Open AccessArticle

Serum and Saliva Level of miR-31-5p and miR-let 7a in EBV Associated Oropharyngeal Cancer

by Anna Polz, Kamal Morshed, Robert Bibik, Bartłomiej Drop, Andrzej Drop and Małgorzata Polz-Dacewicz

Int. J. Mol. Sci. 2023, 24(15), 11965; https://doi.org/10.3390/ijms241511965 - 26 Jul 2023

Viewed by 1414

Abstract

Epstein-Barr virus (EBV) has a well-documented association with head and neck neoplasms, including nasopharyngeal carcinoma (NPC). In the last few years, research aimed at elucidating the role of the miRs in the pathogenesis of head and neck cancer (HNC) has gained importance. The study of miRs expression has set new directions in the search for biomarkers with diagnostic and prognostic value, and even in the search for new therapeutic targets for various tumors, including HNC. The aim of current study was to approximate the importance of miR-31-5p and miR-let 7a in the pathogenesis of EBV associated oropharyngeal cancer. For this purpose, experiments were carried out to determine the level of mentioned miRs in serum among patients diagnosed with oropharyngeal cancer linked to EBV infection, depending on histological differentiation-grading (G1–G3) and TNM classification. All clinical specimens stratified by HPV status were HPV negative. The level of antibodies EBNA and EBVCA was also assessed. The obtained results showed a significantly increased serum level of miR-31-5p but decreased level of miR-let 7a in EBV positive oropharyngeal cancer patients. We demonstrated association between the level of tested miRs and clinical stage. Our findings showed that miR-31-5p and miR-let-7a may be involved in development and progression of EBV associated oropharyngeal cancer. Therefore, it seems important to further study these molecules, as well as to determine whether they could be important biomarkers in the diagnosis of oropharyngeal cancer associated with EBV infection. Full article

(This article belongs to the Special Issue Oral Squamous Cell Carcinoma—Pathogenetic, Diagnostic and Therapeutic Perspectives)

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18 pages, 4361 KiB

Open AccessArticle

Identification of Somatic Mutations in Plasma Cell-Free DNA from Patients with Metastatic Oral Squamous Cell Carcinoma

by Li-Han Lin, Kuo-Wei Chang, Hui-Wen Cheng and Chung-Ji Liu

Int. J. Mol. Sci. 2023, 24(12), 10408; https://doi.org/10.3390/ijms241210408 - 20 Jun 2023

Cited by 2 | Viewed by 2526

Abstract

The accurate diagnosis and treatment of oral squamous cell carcinoma (OSCC) requires an understanding of its genomic alterations. Liquid biopsies, especially cell-free DNA (cfDNA) analysis, are a minimally invasive technique used for genomic profiling. We conducted comprehensive whole-exome sequencing (WES) of 50 paired OSCC cell-free plasma with whole blood samples using multiple mutation calling pipelines and filtering criteria. Integrative Genomics Viewer (IGV) was used to validate somatic mutations. Mutation burden and mutant genes were correlated to clinico-pathological parameters. The plasma mutation burden of cfDNA was significantly associated with clinical staging and distant metastasis status. The genes TTN, PLEC, SYNE1, and USH2A were most frequently mutated in OSCC, and known driver genes, including KMT2D, LRP1B, TRRAP, and FLNA, were also significantly and frequently mutated. Additionally, the novel mutated genes CCDC168, HMCN2, STARD9, and CRAMP1 were significantly and frequently present in patients with OSCC. The mutated genes most frequently found in patients with metastatic OSCC were RORC, SLC49A3, and NUMBL. Further analysis revealed that branched-chain amino acid (BCAA) catabolism, extracellular matrix–receptor interaction, and the hypoxia-related pathway were associated with OSCC prognosis. Choline metabolism in cancer, O-glycan biosynthesis, and protein processing in the endoplasmic reticulum pathway were associated with distant metastatic status. About 20% of tumors carried at least one aberrant event in BCAA catabolism signaling that could possibly be targeted by an approved therapeutic agent. We identified molecular-level OSCC that were correlated with etiology and prognosis while defining the landscape of major altered events of the OSCC plasma genome. These findings will be useful in the design of clinical trials for targeted therapies and the stratification of patients with OSCC according to therapeutic efficacy. Full article

(This article belongs to the Special Issue Oral Squamous Cell Carcinoma—Pathogenetic, Diagnostic and Therapeutic Perspectives)

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12 pages, 3519 KiB

Open AccessArticle

The Concordant Disruption of B7/CD28 Immune Regulators Predicts the Prognosis of Oral Carcinomas

by Shi-Rou Chang, Chung-Hsien Chou, Chung-Ji Liu, Yu-Cheng Lin, Hsi-Feng Tu, Kuo-Wei Chang and Shu-Chun Lin

Int. J. Mol. Sci. 2023, 24(6), 5931; https://doi.org/10.3390/ijms24065931 - 21 Mar 2023

Cited by 8 | Viewed by 2265

Abstract

Immune modulation is a critical factor in determining the survival of patients with malignancies, including those with oral squamous cell carcinoma (OSCC) and head and neck SCC (HNSCC). Immune escape or stimulation may be driven by the B7/CD28 family and other checkpoint molecules, forming ligand–receptor complexes with immune cells in the tumor microenvironment. Since the members of B7/CD28 can functionally compensate for or counteract each other, the concomitant disruption of multiple members of B7/CD28 in OSCC or HNSCC pathogenesis remains elusive. Transcriptome analysis was performed on 54 OSCC tumors and 28 paired normal oral tissue samples. Upregulation of CD80, CD86, PD-L1, PD-L2, CD276, VTCN1, and CTLA4 and downregulation of L-ICOS in OSCC relative to the control were noted. Concordance in the expression of CD80, CD86, PD-L1, PD-L2, and L-ICOS with CD28 members was observed across tumors. Lower ICOS expression indicated a worse prognosis in late-stage tumors. Moreover, tumors harboring higher PD-L1/ICOS, PD-L2/ICOS, or CD276/ICOS expression ratios had a worse prognosis. The survival of node-positive patients was further worsened in tumors exhibiting higher ratios between PD-L1, PD-L2, or CD276 and ICOS. Alterations in T cell, macrophage, myeloid dendritic cell, and mast cell populations in tumors relative to controls were found. Decreased memory B cells, CD8⁺ T cells, and Tregs, together with increased resting NK cells and M0 macrophages, occurred in tumors with a worse prognosis. This study confirmed frequent upregulation and eminent co-disruption of B7/CD28 members in OSCC tumors. The ratio between PD-L2 and ICOS is a promising survival predictor in node-positive HNSCC patients. Full article

(This article belongs to the Special Issue Oral Squamous Cell Carcinoma—Pathogenetic, Diagnostic and Therapeutic Perspectives)

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17 pages, 9400 KiB

Open AccessArticle

Semilicoisoflavone B Induces Apoptosis of Oral Cancer Cells by Inducing ROS Production and Downregulating MAPK and Ras/Raf/MEK Signaling

by Ming-Ju Hsieh, Hsin-Yu Ho, Yu-Sheng Lo, Chia-Chieh Lin, Yi-Ching Chuang, Mosleh Mohammad Abomughaid, Ming-Chang Hsieh and Mu-Kuan Chen

Int. J. Mol. Sci. 2023, 24(5), 4505; https://doi.org/10.3390/ijms24054505 - 24 Feb 2023

Cited by 8 | Viewed by 2321

Abstract

Oral squamous cell carcinoma (OSCC) is the sixth most common type of cancer worldwide. Despite advancement in treatment, advanced-stage OSCC is associated with poor prognosis and high mortality. The present study aimed to investigate the anticancer activities of semilicoisoflavone B (SFB), which is a natural phenolic compound isolated from Glycyrrhiza species. The results revealed that SFB reduces OSCC cell viability by targeting cell cycle and apoptosis. The compound caused cell cycle arrest at the G2/M phase and downregulated the expressions of cell cycle regulators including cyclin A and cyclin-dependent kinase (CDK) 2, 6, and 4. Moreover, SFB induced apoptosis by activating poly-ADP-ribose polymerase (PARP) and caspases 3, 8, and 9. It increased the expressions of pro-apoptotic proteins Bax and Bak, reduced the expressions of anti-apoptotic proteins Bcl-2 and Bcl-xL, and increased the expressions of the death receptor pathway protein Fas cell surface death receptor (FAS), Fas-associated death domain protein (FADD), and TNFR1-associated death domain protein (TRADD). SFB was found to mediate oral cancer cell apoptosis by increasing reactive oxygen species (ROS) production. The treatment of the cells with N-acetyl cysteine (NAC) caused a reduction in pro-apoptotic potential of SFB. Regarding upstream signaling, SFB reduced the phosphorylation of AKT, ERK1/2, p38, and JNK1/2 and suppressed the activation of Ras, Raf, and MEK. The human apoptosis array conducted in the study identified that SFB downregulated survivin expression to induce oral cancer cell apoptosis. Taken together, the study identifies SFB as a potent anticancer agent that might be used clinically to manage human OSCC. Full article

(This article belongs to the Special Issue Oral Squamous Cell Carcinoma—Pathogenetic, Diagnostic and Therapeutic Perspectives)

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16 pages, 1153 KiB

Open AccessArticle

Chemotherapeutic Drug Resistance Associated with Differential miRNA Expression of miR-375 and miR-27 among Oral Cancer Cell Lines

by Kieran Caberto Huni, Jacky Cheung, Madeline Sullivan, William Taylor Robison, Katherine M. Howard and Karl Kingsley

Int. J. Mol. Sci. 2023, 24(2), 1244; https://doi.org/10.3390/ijms24021244 - 8 Jan 2023

Cited by 9 | Viewed by 2117

Abstract

Recent advances have suggested that non-coding miRNAs (such as miR-21, miR-27, miR-145, miR-155, miR-365, miR-375 and miR-494) may be involved in multiple aspects of oral cancer chemotherapeutic responsiveness. This study evaluated whether these specific miRNAs are correlated with oral cancer responsiveness to chemotherapies, including Paclitaxel, Cisplatin and Fluorouracil (5FU). Commercially available and well-characterized oral squamous cell carcinoma cell lines (SCC4, SCC9, SCC15, SCC25 and CAL27) revealed differing resistance and chemosensitivity to these agents—with SCC9 and SCC25 demonstrating the most resistance to all chemotherapeutic agents. SCC9 and SCC25 were also the only cell lines that expressed miR-375, and were the only cell lines that did not express miR-27. In addition, the expression of miR-375 was associated with the upregulation of Rearranged L-myc fusion (RLF) and the downregulation of Centriolar protein B (POC1), whereas lack of miR-27 expression was associated with Nucleophosmin 1 (NPM1) expression. These data have revealed important regulatory pathways and mechanisms associated with oral cancer proliferation and resistance that must be explored in future studies of potential therapeutic interventions. Full article

(This article belongs to the Special Issue Oral Squamous Cell Carcinoma—Pathogenetic, Diagnostic and Therapeutic Perspectives)

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19 pages, 2278 KiB

Open AccessArticle

Role Played by Paraoxonase-2 Enzyme in Cell Viability, Proliferation and Sensitivity to Chemotherapy of Oral Squamous Cell Carcinoma Cell Lines

by Roberto Campagna, Alessia Belloni, Valentina Pozzi, Alessia Salvucci, Valentina Notarstefano, Lucrezia Togni, Marco Mascitti, Davide Sartini, Elisabetta Giorgini, Eleonora Salvolini, Andrea Santarelli, Lorenzo Lo Muzio and Monica Emanuelli

Int. J. Mol. Sci. 2023, 24(1), 338; https://doi.org/10.3390/ijms24010338 - 25 Dec 2022

Cited by 19 | Viewed by 2250

Abstract

Oral squamous cell carcinoma represents the most aggressive and frequent form of head and neck cancer. Due to drug resistance, the 5-year survival rate of patients with advanced disease is less than 50%. In order to identify molecular targets for effective oral cancer treatment, we focused on paraoxonase-2 enzyme. Indeed, based on data previously obtained from preliminary immunohistochemistry and Western blot analyses performed on tissue specimens, the enzyme was found to be upregulated in tumor compared with normal oral mucosa. Therefore, paraoxonase-2 gene silencing was achieved in HSC-3 and HOC621 oral cancer cell lines, and the effect on cell proliferation, viability, apoptosis induction and sensitivity to cisplatin and 5-fluorouracil treatment was evaluated. Fourier Transform InfraRed Microspectroscopy analyzed alterations of cellular macromolecules upon treatment. Enzyme level and cell proliferation were also determined in cisplatin-resistant clones obtained from HOC621 cell line, as well as in parental cells. Reported data showed that paraoxonase-2 knockdown led to a reduction of cell proliferation and viability, as well as to an enhancement of sensitivity to cisplatin, together with the activation of apoptosis pathway. Spectroscopical data demonstrated that, under treatment with cisplatin, oxidative damage exerted on lipids and proteins was markedly more evident in cells down-regulating paraoxonase-2 compared to controls. Interestingly, enzyme expression, as well as cell proliferation were significantly higher in cisplatin-resistant compared with control HOC621 cells. Taken together these results seem to candidate the enzyme as a promising target for molecular treatment of this neoplasm. Full article

(This article belongs to the Special Issue Oral Squamous Cell Carcinoma—Pathogenetic, Diagnostic and Therapeutic Perspectives)

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Review

Jump to: Editorial, Research

20 pages, 899 KiB

Open AccessReview

Role of Cannabinoids in Oral Cancer

by Brigitte Cretu, Alexandra Zamfir, Sandica Bucurica, Andreea Elena Scheau, Ilinca Savulescu Fiedler, Constantin Caruntu, Ana Caruntu and Cristian Scheau

Int. J. Mol. Sci. 2024, 25(2), 969; https://doi.org/10.3390/ijms25020969 - 12 Jan 2024

Cited by 1 | Viewed by 4210

Abstract

Cannabinoids have incited scientific interest in different conditions, including malignancy, due to increased exposure to cannabis. Furthermore, cannabinoids are increasingly used to alleviate cancer-related symptoms. This review paper aims to clarify the recent findings on the relationship between cannabinoids and oral cancer, focusing on the molecular mechanisms that could link cannabinoids with oral cancer pathogenesis. In addition, we provide an overview of the current and future perspectives on the management of oral cancer patients using cannabinoid compounds. Epidemiological data on cannabis use and oral cancer development are conflicting. However, in vitro studies assessing the effects of cannabinoids on oral cancer cells have unveiled promising anti-cancer features, including apoptosis and inhibition of cell proliferation. Downregulation of various signaling pathways with anti-cancer effects has been identified in experimental models of oral cancer cells exposed to cannabinoids. Furthermore, in some countries, several synthetic or phytocannabinoids have been approved as medical adjuvants for the management of cancer patients undergoing chemoradiotherapy. Cannabinoids may improve overall well-being by relieving anxiety, depression, pain, and nausea. In conclusion, the link between cannabinoid compounds and oral cancer is complex, and further research is necessary to elucidate the potential risks or their protective impact on oral cancer. Full article

(This article belongs to the Special Issue Oral Squamous Cell Carcinoma—Pathogenetic, Diagnostic and Therapeutic Perspectives)

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16 pages, 1462 KiB

Open AccessReview

Comparison of Immunohistochemical Markers in Oral Submucous Fibrosis and Oral Submucous Fibrosis Transformed to Oral Squamous Cell Carcinoma—A Systematic Review and Meta-Analysis

by Diksha Mohapatra, Swagatika Panda, Neeta Mohanty, Saurav Panda, Natalia Lewkowicz and Barbara Lapinska

Int. J. Mol. Sci. 2023, 24(14), 11771; https://doi.org/10.3390/ijms241411771 - 21 Jul 2023

Cited by 2 | Viewed by 2420

Abstract

The objective of the study was to compare the expression of immunohistochemical (IHC) markers of oral submucous fibrosis (OSMF) (non-transformed group) to those of oral squamous cell carcinoma (OSCC) transformed from OSMF (transformed group). The search for comparative cross-sectional studies was carried out in PubMed and Scopus abiding to the PICO criteria, where expression of IHC markers in OSMF were compared with that of OSCC transformed from OSMF. The cellular distribution, number of positive cases, staining intensity, and mean immunoreactive score (IRS) of each IHC marker were evaluated in both groups. A total of 14 studies were included in the systematic review, in which immunoexpression of 15 epithelial and 4 connective tissue biomarkers were evaluated. Expression of β1-integrin, OCT-3, CD1a, CD207, survivin, Dickkopf-1, COX-2, hTERT, CTGF, MDM2, Ki-67, and α-SMA were increased during transformation of OSMF to OSCC. Conversely, expression of PTEN and lysyl oxidase decreased during transformation of OSMF to OSCC. Expression of a group of epithelial markers, such as COX2, hTERT, CTGF, survivin, MDM2, and p53, was 38 times lower in the non-transformed group cases compared to transformed group cases (95% CI: 58% to 10%; p = 0.01; and I² = 90%). Meta-analysis of all markers involved in cell metabolism/apoptosis, which included β1-integrin along with the above markers also suggested 42 times lower expression in the non-transformed group as compared to the transformed group (95% CI: 58% to 10%; p = 0.01; and I² = 90%). Sub-group analyses on cytoplasmic and nuclear epithelial markers were inconclusive. Meta-analysis of connective tissue markers was also inconclusive. No publication bias was found. Instead of delving into numerous markers without a strong basis for their use, it is advisable to further study the markers identified in this study to explore their clinical utility. Full article

(This article belongs to the Special Issue Oral Squamous Cell Carcinoma—Pathogenetic, Diagnostic and Therapeutic Perspectives)

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