The clinicopathological significance and prognostic value of PD-L1 in oral squamous cell carcinoma.

OBJECTIVE: To investigate the relationship between the expression of PD-L1 in OSCC and the clinicopathological features and prognosis of patients. METHODS: We retrospectively analyzed the clinicopathological data and prognosis of 381 OSCC patients. Immunohistochemical staining was performed on OSCC tumor specimens, and the expression level of PD-L1 was evaluated according to the combined positive score (CPS). Kaplan-Meier analysis was used to identify the effect of PD-L1 expression and clinicopathological features on the prognosis of patients. Univariate and multivariate Cox regression analyses were conducted to determine the hazard factors affecting the prognosis of patients. RESULTS: PD-L1 overexpression was significantly associated with cervical lymph node metastasis (p = 0.018), worse clinical stage (p = 0.022), worse tumor differentiation (p = 0.046), and worse depth of invasion (DOI) (p = 0.003). Poorer clinical stage and degree of tumor differentiation were significantly associated with poorer OS and DSS in patients. PD-L1 expression was not associated with prognosis in patients with OSCC. CONCLUSIONS: High PD-L1 expression was significantly associated with higher tumor malignancy in OSCC patients. Poorer clinical stage and degree of tumor differentiation were associated with poor prognosis in OSCC patients. Our results may help clinicians develop more appropriate individualized treatment strategies for their patients, thus improving their outcomes.

Circ-CDK8 regulates SLC7A11-mediated ferroptosis by inhibiting miR-615-5p to promote progression in oral squamous cell carcinomas.

Introduction: Ferroptosis is a new mode of programmed cell death distinct from necrosis, apoptosis, and autophagy, induced by iron-ion-dependent lipid peroxide accumulation. Circular RNAs are a class of endogenous non-coding RNAs that regulate the biological behavior of tumors. However, the role of circ-CDK8 in regulating ferroptosis, migration, and invasion of oral squamous cell carcinoma (OSCC) remains unknown. Methods: The effect of circ-CDK8 on OSCC cell ferroptosis, migration, and invasion was evaluated using CCK-8, wound healing, transwell, reactive oxygen species (ROS), malondialdehyde (MDA), and GSH assays and Western blotting. Bioinformatics analyses and luciferase reporter assays were performed and revealed targeted relationships between circ-CDK8 and miR-615-5p, miR-615-5p and SLC7A11. Interference with circ-CDK8 expression reduced SLC7A11 expression by sponging miR-615-5p, suppressed OSCC cell migration and invasion, and promoted ferroptosis by increasing ROS, MDA, and iron levels and decreasing GSH and GPX4 levels in OSCC cells. Furthermore, in vivo, animal experiments confirmed that circ-CDK8 interference inhibited OSCC cell proliferation and SLC7A11 expression. Results: Collectively, this study revealed a novel strategy to upregulate erastin-induced ferroptosis in OSCC cells via the circ-CDK8/miR-615-5p/SLC7A11 axis, providing new insights into OSCC and a potential therapeutic strategy for OSCC.

Role of O-linked N-acetylglucosamine protein modification in oxidative stress-induced autophagy: a novel target for bone remodeling.

O-linked N-acetylglucosamine protein modification (O-GlcNAcylation) is a dynamic post-translational modification (PTM) involving the covalent binding of serine and/or threonine residues, which regulates bone cell homeostasis. Reactive oxygen species (ROS) are increased due to oxidative stress in various pathological contexts related to bone remodeling, such as osteoporosis, arthritis, and bone fracture. Autophagy serves as a scavenger for ROS within bone marrow-derived mesenchymal stem cells, osteoclasts, and osteoblasts. However, oxidative stress-induced autophagy is affected by the metabolic status, leading to unfavorable clinical outcomes. O-GlcNAcylation can regulate the autophagy process both directly and indirectly through oxidative stress-related signaling pathways, ultimately improving bone remodeling. The present interventions for the bone remodeling process often focus on promoting osteogenesis or inhibiting osteoclast absorption, ignoring the effect of PTM on the overall process of bone remodeling. This review explores how O-GlcNAcylation synergizes with autophagy to exert multiple regulatory effects on bone remodeling under oxidative stress stimulation, indicating the application of O-GlcNAcylation as a new molecular target in the field of bone remodeling.

Prognostic effect of surgical treatment in elderly oral squamous cell carcinoma patients: A retrospective study.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is one of the most prevalent malignant tumors in head and neck. However, few studies have focused on the postoperative prognosis of elderly OSCC patients undergoing surgical resection and reconstruction. METHODS: We conducted a retrospective study of 349 patients diagnosed OSCC in the Department of Oral and Maxillofacial Surgery, The Affiliated Hospital of Qingdao University from January 2016 to December 2022. Demographic and clinicopathological characteristics were recorded. Kaplan-Meier analysis was performed to identify the impact of age and reconstruction types on the prognosis of OSCC patients. Univariable regression analysis and multivariable Cox analysis were conducted to find independent prognostic factors of the younger and elderly OSCC patients. RESULTS: Among 349 OSCC patients included in this retrospective study, 241 (69.1 %) were elderly patients and 108 (30.9 %) were younger patients. The two groups were comparable according to the demographic records. The elderly group presented a better recurrence-specific prognosis than that of the younger group (RFS: p = 0.0324). There are no remarkable differences on the prognosis of different reconstructive types. Gender, current address, life habit, invasion patterns, and TNM stage were identified as independent prognostic factors of the younger and elderly OSCC patients. CONCLUSION: Elderly OSCC patients achieve a better recurrence-free survival than that of the younger patients. Meanwhile, the recurrence of OSCC patients is independent of their demographic and clinicopathological features. Elderly OSCC patients will benefit from aggressive surgical treatment as the younger patients.

O-GlcNAcylation: roles and potential therapeutic target for bone pathophysiology.

O-linked N-acetylglucosamine (O-GlcNAc) protein modification (O-GlcNAcylation) is a critical post-translational modification (PTM) of cytoplasmic and nuclear proteins. O-GlcNAcylation levels are regulated by the activity of two enzymes, O-GlcNAc transferase (OGT) and O­GlcNAcase (OGA). While OGT attaches O-GlcNAc to proteins, OGA removes O-GlcNAc from proteins. Since its discovery, researchers have demonstrated O-GlcNAcylation on thousands of proteins implicated in numerous different biological processes. Moreover, dysregulation of O-GlcNAcylation has been associated with several pathologies, including cancers, ischemia-reperfusion injury, and neurodegenerative diseases. In this review, we focus on progress in our understanding of the role of O-GlcNAcylation in bone pathophysiology, and we discuss the potential molecular mechanisms of O-GlcNAcylation modulation of bone-related diseases. In addition, we explore significant advances in the identification of O-GlcNAcylation-related regulators as potential therapeutic targets, providing novel therapeutic strategies for the treatment of bone-related disorders.

Primary cutaneous anaplastic large-cell lymphoma resembling infratemporal space infection: a case report.

BACKGROUND: Primary cutaneous anaplastic large-cell lymphoma (PC-ALCL) is a rare T-cell lymphoma belonging to the CD30 + T-cell lymphoproliferative disorders. The case of PC-ALCL in the temporal region is exceedingly rare. Herein, we report a case of PC-ALCL involving the temporal region mimicking infratemporal space infection. CASE PRESENTATION: A 78-year-old woman presented to maxillofacial surgery service with a 6-month history of swelling and pain in the left side of her face. Laboratory investigations found an elevated C-reactive protein (CRP). Imaging findings showed enlarged lymph nodes and extensive thickening of subcutaneous tissue of the left temples. Based on these findings, the infratemporal space infection was suspected initially. The patient underwent incision and drainage, and we unexpectedly found no pus in the lesion area. Incisional biopsy showed necrosis and extensive involvement of the left temples by a diffuse infiltrate containing large, atypical cells. The tumor cells were positive for CD30, CD3, Ki67. They were negative for ALK (SP8), CD5, CD8, CD20 and PAX5. After considering these findings, a diagnosis of PC-ALCL was rendered. The patient was admitted to the lymphoma department for systemic chemotherapy and no relapse occurred during a follow-up period of six months. CONCLUSIONS: This report suggests that if there are suspicious intraoperative manifestations, carrying out a biopsy simultaneously, using Hematoxylin and eosin (HE) staining, and a comprehensive Immunohistochemistry (IHC) panel are essential to diagnosing PC-ALCL to prevent misdiagnosis.

Functional significance of O-linked N-acetylglucosamine protein modification in regulating autophagy.

Autophagy is a core molecular pathway that preserves cellular and organismal homeostasis. Being susceptible to nutrient availability and stress, eukaryotic cells recycle or degrade internal components via membrane transport pathways to provide sustainable biological molecules and energy sources. The dysregulation of this highly conserved physiological process has been strongly linked to human disease. Post-translational modification, a mechanism that regulates protein function, plays a crucial role in autophagy regulation. O-linked N-acetylglucosamine protein modification (O-GlcNAcylation), a monosaccharide post-translational modification of intracellular proteins, is essential in nutritional and stress regulatory mechanisms. O-GlcNAcylation has emerged as an essential regulatory mechanism of autophagy. It regulates autophagy throughout its lifetime by targeting the core components of the autophagy regulatory network. This review provides an overview of the O-GlcNAcylation of autophagy-associated proteins and their regulation and function in the autophagy pathway. Therefore, this article may contribute to further understanding of the role of O-GlcNAc-regulated autophagy and provide new perspectives for the treatment of human diseases.

Review: Protein O-GlcNAcylation regulates DNA damage response: A novel target for cancer therapy.

The DNA damage response (DDR) safeguards the stable genetic information inheritance by orchestrating a complex protein network in response to DNA damage. However, this mechanism can often hamper the effectiveness of radiotherapy and DNA-damaging chemotherapy in destroying tumor cells, causing cancer resistance. Inhibiting DDR can significantly improve tumor cell sensitivity to radiotherapy and DNA-damaging chemotherapy. Thus, DDR can be a potential target for cancer treatment. Post-translational modifications (PTMs) of DDR-associated proteins profoundly affect their activity and function by covalently attaching new functional groups. O-GlcNAcylation (O-linked-N-acetylglucosaminylation) is an emerging PTM associated with adding and removing O-linked N-acetylglucosamine to serine and threonine residues of proteins. It acts as a dual sensor for nutrients and stress in the cell and is sensitive to DNA damage. However, the explanation behind the specific role of O-GlcNAcylation in the DDR remains remains to be elucidated. To illustrate the complex relationship between O-GlcNAcylation and DDR, this review systematically describes the role of O-GlcNAcylation in DNA repair, cell cycle, and chromatin. We also discuss the defects of current strategies for targeting O-GlcNAcylation-regulated DDR in cancer therapy and suggest potential directions to address them.

The mitochondrial regulation in ferroptosis signaling pathway and its potential strategies for cancer.

Ferroptosis is an iron-dependent regulated cell death, mainly manifested by the production of reactive oxygen species and accumulation of lipid peroxides. It is distinct from other forms of cell death with regard to morphology and biochemistry, particularly in disrupting mitochondrial function. Mitochondria are essential compartments where the organism generates energy and are closely associated with the fate of ferroptosis. Currently, researchers focus on the potential value of ferroptosis and mitochondria for overcoming drug sensitivity and assisting in cancer therapy. In this review, we summarize the main mechanisms of ferroptosis (the GPX4-realated pathway, FSP1-related pathway, and iron metabolism pathway) and the functions and regulating pathways of mitochondria (the TCA cycle, oxidative phosphorylation, mitochondrial regulation of iron ions, and mtDNA) in ferroptosis. We believe that exploring the role of mitochondria in ferroptosis will help us understand the potential regulatory mechanisms of ferroptosis in cancer and help us find new therapeutic targets.

The role of novel programmed cell death in head and neck squamous cell carcinoma: from mechanisms to potential therapies.

Head and neck squamous cell carcinoma (HNSCC) is a common oral cancer with poor prognosis and for which no targeted therapeutic strategies are currently available. Accumulating evidence has demonstrated that programmed cell death (PCD) is essential in the development of HNSCC as a second messenger. PCD can be categorized into numerous different subroutines: in addition to the two well-known types of apoptosis and autophagy, novel forms of programmed cell death (e.g., necroptosis, pyroptosis, ferroptosis, and NETosis) also serve as key alternatives in tumorigenesis. Cancer cells are not able to avoid all types of cell death simultaneously, since different cell death subroutines follow different regulatory pathways. Herein, we summarize the roles of novel programmed cell death in tumorigenesis and present our interpretations of the molecular mechanisms with a view to the development of further potential therapies.

Expression of YT Domain Family Protein in Oral Squamous Cell Carcinoma and Its Correlation with the Prognosis.

Background: Proteins contained in the conserved YTH521-b homologous (YTH) domain, have m6A-dependent RNA binding activity. As an important part of YTH domain family proteins, YTHDF1 and YTHDF3 were shown to be associated with many cancers. This paper aimed to reveal the relationship between the expression of these two proteins and the clinical prognosis of OSCC, providing certain guidance for clinical treatment of OSCC. Methods: We detected the expression of YTHDF1 and YTHDF3 in 120 OSCC patients by immunohistochemical analysis. Statistical analysis was used to determine whether the high or low expression of these two genes was significantly associated with age, gender, histological type, clinical stage, or lymph node metastasis. The correlation curve and survival curve of the two genes were produced to evaluate the potential clinical significance. Results: We find the expression of YTHDF1 and YTHDF3 was increased in OSCC tissues compared to adjacent normal tissues. The statistical analysis showed that the expression of YTHDF1 and YTHDF3 was significantly associated with the clinical stage and histological type in OSCC patients. There was also a significant correlation between the expression of YTHDF1 and YTHDF3. A high expression of YTHDF1 and YTHDF3 was related to poor patient prognosis. Conclusion: Our findings suggest that a high expression of YTHDF1 and YTHDF3 may be related to poor patient prognosis.

Prognostic significance of CircRNAs expression in oral squamous cell carcinoma.

This systematic review was aimed to comprehensively evaluate the clinicopathological and prognostic value of dysregulated expression of circRNAs in OSCC. The research was carried out by searching mainstream electronic databases including PubMed, Embase, Web of Science, Scopus, LILACS, and Cochrane Library to collect relevant studies on prognostic role of circRNAs in OSCC. Pooled hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the association between circRNAs expression, overall survival (OS), disease/recurrence/progression survival (DFS/RFS/PFS), and clinical parameters. This research included 1813 patients from 26 selected articles. The pooled HR values (95% CIs) in OS were 2.38 (1.92-2.93) for oncogenic circRNAs and 0.43 (0.28-0.66) for tumor-suppressor circRNAs, respectively, in DFS/RFS/PFS were 2.34 (1.73-3.17). The meta-analysis on clinicopathology features showed higher level of oncogenic circRNAs is related to advanced TNM stage, tumor stage, worse histological differentiation, positive lymph node and distant metastasis, while enforced expression of tumor-suppressor circRNAs is related to inferior TNM stage, tumor stage and lymphatic metastasis. In conclusion, our meta-analysis implies that circRNAs may be candidate biomarkers for the prognosis and clinicopathology of OSCC.

The microRNA-10b-Bim axis promotes cancer progression through activating autophagy in oral squamous cell carcinoma.

Autophagy is related to many cellular mechanisms and dysregulation of autophagy involves the pathological process in cancer. miR-10b activates autophagy, which promotes invasion and migration of OSCC. Its functional role in the mechanism of OSCC to autophagy remains to be unclear. Overexpression of miR-10b was followed by enhanced OSCC invasion and migration and activated autophagic protein, such as LC3II/ATG5. MiR-10b attracted Bim directly according to the Bio-informatics analyses and double luciferases reporter assays. Functional experiments further revealed that miR-10b could promote invasion and migration in vitro. In addition, miR-10b induced autophagy via inhibiting Bim in invasion and migration of OSCC. Notably, animal experiments confirmed that miR-10b-Bim promoted proliferation and autophagy in OSCC. In addition, this study provides a theoretical support for regulating the mechanism of OSCC by inducing autophagy with miR-10b-Bim as a target.