Metastasis Of Oral Squamous Cell Carcinoma Research Articles

Abstract 6992: Profilin 2 (PFN2) promotes the proliferation, migration, invasion and epithelial-to-mesenchymal transition of oral squamous cell carcinoma

Abstract Background:Oral squamous cell carcinoma (OSCC) stands as a prevalent malignancy worldwide. Profilin 2 (PFN2), an actin-binding protein regulating actin polymerization dynamics and associated with cell motility, has recently gained attention as a significant regulator in various cancers. However, the clinical significance and biological function of PFN2 in OSCC remain debatable. This study aims to elucidate the role of PFN2 in OSCC. Methods:We assessed PFN2 expression in OSCC and adjacent normal oral mucosa tissues through Q-RT-PCR and immunohistochemistry analysis. Associations between PFN2 expression, clinicopathological features, and OSCC prognosis were analyzed. Cell proliferation, invasion, and migration effects were examined via MTT and Transwell assays. Western blotting assessed the protein expression related to epithelial–mesenchymal transition (EMT). Additionally, we established OSCC xenografts to determine tumorigenicity in vivo using female Nude mice. Results:PFN2 RNA and protein expression were significantly increased in OSCC compared to normal oral mucosa. PFN2 expression positively correlated with lymphovascular invasion and cervical lymph node metastasis. MTT and Transwell assays demonstrated that PFN2 promoted OSCC cell proliferation, migration, invasion, and endothelial invasion. Downregulation of PFN2 induced an EMT phenotype, including an increase in the expression of the epithelial marker E-cadherin and a decrease in the expression of mesenchymal markers Vimentin, Snail, and Slug in OSCC cells in vitro. Similarly, OSCC cells with reduced PFN2 expression exhibited weaker tumorigenicity in vivo. Conclusions:Our findings unveil a novel role for PFN2 in promoting OSCC progression and metastasis, suggesting its potential as an early biomarker for high-risk populations. Targeting PFN2 may offer a promising therapeutic strategy for OSCC treatment. Citation Format: Chung Ji LIu, Li-Han Lin, Kuo-Wei Chang, Hui-Wen Cheng. Profilin 2 (PFN2) promotes the proliferation, migration, invasion and epithelial-to-mesenchymal transition of oral squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6992.

EMT Dynamics in Lymph Node Metastasis of Oral Squamous Cell Carcinoma.

Epithelial-mesenchymal transition (EMT) enables tumor cell invasion and metastasis. Many studies have demonstrated the critical role of EMT in lymph node metastasis in oral squamous cell carcinoma (OSCC). During EMT, epithelial cancer cells lose intercellular adhesion and apical-basal polarity and acquire mesenchymal properties such as motility and invasiveness. A significant feature of EMT is cadherin switching, involving the downregulation of E-cadherin and upregulation of N-cadherin. The TGF-β/SMAD pathway can also induce EMT. We aimed to evaluate EMT markers as predictors of lymph node metastasis in OSCC. We performed genetic profiling of 159 primary OSCCs from TCGA and analyzed the expression of EMT markers, including cadherin switch genes (CDH1, CDH2), and TGF-β/SMAD pathway genes. Samples were divided into advanced (stage III-IV) and early (stage I-II) stage groups. Differential expression analysis was performed, as well as an independent validation study containing fresh OSCC samples. TGF-β/SMAD pathway genes such as SMAD6 were upregulated in advanced stage tumors. N-cadherin and SNAIL2 were overexpressed in node-positive tumors. Keratins were downregulated in these groups. Our findings demonstrate that EMT marker expression correlates with lymph node metastasis in OSCC. Developing therapies targeting regulators such as N-cadherin may prevent metastasis and improve outcomes.

NANOS1 restricts oral cancer cell motility and TGF-ß signaling

Oral squamous cell carcinoma (OSCC) is the most frequent type of cancer of the head and neck area accounting for approx. 377,000 new cancer cases every year. The epithelial-to-mesenchymal transition (EMT) program plays an important role in OSCC progression and metastasis therefore contributing to a poor prognosis in patients with advanced disease. Transforming growth factor beta (TGF-ß) is a powerful inducer of EMT thereby increasing cancer cell aggressiveness. Here, we aimed at identifying RNA-binding proteins (RBPs) that affect TGF-ß-induced EMT. To this end we treated oral cancer cells with TGF-ß and identified a total of 643 significantly deregulated protein-coding genes in response to TGF-ß. Of note, 19 genes encoded RBPs with NANOS1 being the most downregulated RBP. Subsequent cellular studies demonstrated a strong inhibitory effect of NANOS1 on migration and invasion of SAS oral cancer cells. Further mechanistic studies revealed an interaction of NANOS1 with the TGF-ß receptor 1 (TGFBR1) mRNA, leading to increased decay of this transcript and a reduced TGFBR1 protein expression, thereby preventing downstream TGF-ß/SMAD signaling. In summary, we identified NANOS1 as negative regulator of TGF-ß signaling in oral cancer cells.

Prognostic significance of RKIP, TGM2, and CMTM4 expression in oral squamous cell carcinoma.

The expression of RKIP, TGM2, and CMTM4 in oral squamous cell carcinoma (OSCC) and normal oral tissues was detected and their correlations were analyzed. The relationships between RKIP, TGM2, and CMTM4 and the clinicopathological parameters and prognosis of patients were analyzed. Seventy cancerous and adjacent normal tissue samples were selected, recorded in the pathology department, and embedded in paraffin. Protein expression was detected by immunohistochemistry. Statistical software (SPSS 25.0, IBM Corporation) was used for the statistical analysis. The chi-squared (χ2) test was used to analyze the expression of RKIP, TGM2, and CMTM4 proteins and their clinicopathological features. Differences in RKIP, TGM2, and CMTM4 protein levels between OSCC and normal tissues were compared using a χ2 test. Survival analysis was performed using the Kaplan-Meier method, and differences between survival curves were determined using the log-rank test. The effects of RKIP, TGM2, and CMTM4 expression on patient prognosis were analyzed using a multivariate Cox proportional hazards regression model. P < .05 was considered statistically significant. The expression level of RKIP correlated with age and clinical stage (P < .05). TGM2 was associated with clinical stage and lymph node metastasis (P < .05). The expression of CMTM4 increased with a decrease in cancer differentiation. Kaplan-Meier survival analysis suggested that the positive expression of TGM2 and CMTM4 may predict poor prognosis in patients with OSCC. The multivariate Cox proportional hazards regression model suggested that TGM2 could be an independent prognostic factor for patients with OSCC. Combined expression of TGM2 and CMTM4 can be used as an indicator to evaluate the risk of metastasis and prognosis of OSCC.

RUNX1/miR-429 feedback loop promotes growth, metastasis, and epithelial-mesenchymal transition in oral squamous cell carcinoma by targeting ITGB1.

This study aimed to explore the role of miR-429 on the progression of oral squamous cell carcinoma (OSCC). OSCC cell lines were transfected with miR-429 mimic, pcDNA3.1-RUNX1, or pcDNA3.1-ITGB1, and their cell viability, apoptosis, migration, and invasion abilities were analyzed by cell counting, terminal deoxynucleotidyl transferase dUTP nick-end labeling staining, wound healing, and transwell assays, respectively. Furthermore, luciferase reporter assay, RNA pull-down, and ChIP were used to assess the regulation of miR-429, RUNX1, and ITGB1 expression in OSCC. Lastly, the biological role of the RUNX1/miR-429 feedback loop was explored in nude mice. The results revealed that miR-429 level was down-regulated, while RUNX1 and ITGB1 levels were up-regulated in OSCC tissues and that miR-429 was negatively correlated with RUNX1 and ITGB1 in OSCC tissues. Transfection of miR-429 mimic suppressed OSCC cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT). Moreover, we found that miR-429 participated in OSCC progression by directly targeting ITGB1. Additionally, we found that RUNX1 negatively regulated miR-429 expression by binding to its promoter. Our results also revealed that the RUNX1/miR-429 feedback loop regulated ITGB1 expression and that RUNX1 overexpression rescued the inhibitory effects of miR-429 mimic on OSCC cells. In addition, miR-429 mimic significantly suppressed tumor growth, inflammatory cell infiltration, EMT, and ITGB1 expression in vivo, which were inhibited by RUNX1 overexpression. Altogether, these results indicate that the RUNX1/miR-429 feedback loop promoted growth, metastasis, and EMT in OSCC by targeting ITGB1.

Cancer-Associated Fibroblast Heterogeneity in Malignancy with Focus on Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma (OSCC) remains an understudied and significant global cancer killer and dismal survival rates have not changed in decades. A better understanding of the molecular basis of OSCC progression and metastasis is needed to develop new approaches for treating this disease. The supportive network surrounding cancer tumor cells known as the tumor microenvironment (TME) has gained increasing interest lately since it performs essential protumorigenic functions. Cancer-associated fibroblasts (CAFs) are one of the main cell types in the TME and are known to play a key role in influencing the biological behavior of tumors. CAFs present a heterogeneity both in phenotype as well as functions, leading to the suggestion of different CAF subtypes in several cancer forms. The task to subtype CAFs in OSCC has, however, just begun, and there is today no united way of subtyping CAFs in this disease. This review aims to define the features of CAFs and to summarize CAF subtype research in malignancy with focus on OSCC including aspects as disease prognosis and therapeutic opportunities.

Development of an in vitro microfluidic model to study the role of microenvironmental cells in oral cancer metastasis.

Metastasis occurs when cancer cells leave the primary tumour and travel to a secondary site to form a new lesion. The tumour microenvironment (TME) is recognised to greatly influence this process, with for instance the vascular system enabling the dissemination of the cells into other tissues. However, understanding the exact role of these microenvironmental cells during metastasis has proven challenging. Indeed, in vitro models often appear too simplistic, and the study of the interactions between different cell types in a 3D space is limited. On the other hand, even though in vivo models incorporate the TME, observing cells in real-time to understand their exact role is difficult. Horizontal compartmentalised microfluidic models are a promising new platform for metastasis studies. These devices, composed of adjacent microchannels, can incorporate multiple cell types within a 3D space. Furthermore, the transparency and thickness of these models also enables high quality real-time imaging to be performed. This paper demonstrates how these devices can be successfully used for oral squamous cell carcinoma (OSCC) metastasis studies, focusing on the role of the vascular system in this process. Conditions for co-culture of OSCC cells and endothelial cells have been determined and staining protocols optimised. Furthermore, several imaging analysis techniques for these models are described, enabling precise segmentation of the different cell types on the images as well as accurate assessment of their phenotype. These methods can be applied to any study aiming to understand the role of microenvironmental cell types in cancer metastatic dissemination, and overcome several challenges encountered with current in vitro and in vivo models. Hence, this new in vitro model capable of recapitulating important aspects of the cellular complexity of human metastatic dissemination can ultimately contribute to replacing animal studies in this field.

SALIVARY IL-6 AND IL-8 AS POTENTIAL BIOMARKERS FOR ORAL SQUAMOUS CELL CARCINOMA

Introduction: Early identification of oral squamous cell carcinoma (OSCC) is a crucial factor influencing the disease's prognosis. The elevated levels of IL-6 and IL-8 in saliva are a result of their overproduction in the cancer microenvironment. The production of salivary cytokines, particularly IL-6 and IL-8, has a role in cancer development. These cytokines may also be used as biomarkers. The use of saliva as a biomarker is quite interesting because it is in direct contact with cancer cells, easy to access, non-invasive, and cost-effective. Aim: The aim of this literature review was to assess the potential of salivary IL-6 and IL-8 as biomarkers for OSCC early diagnosis. Review: The initiation of carcinogenesis in the oral cavity is actively repressed by inflammation and cell-mediated immunity. IL-6 and IL-8 are two important molecules involved in stromal-to-cancer cell communication. These cytokines play a major part in the growth, progression, metastasis, and recurrence of OSCC. Several studies have found that OSCC patients have higher levels of salivary IL-6 and IL-8 than healthy people and patients with an oral potentially malignant disorder (OPMD). Conclusion: Salivary IL-6 and IL-8 are very promising potential biomarkers for the early diagnosis of OSCC. Further research is still needed to validate and use these biomarkers clinically.

Matrix-based molecular mechanisms, targeting and diagnostics in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is a head and neck cancer (HNC) with a high mortality rate. OSCC is developed in the oral cavity and it is triggered by many etiologic factors and can metastasize both regionally and distantly. Recent research advances in OSCC improved our understanding on the molecular mechanisms involved in and the initiation of OSCC metastasis. The key roles of the extracellular matrix (ECM) in OSCC are an emerging area of intensive research as the ECM macromolecular network is actively involved in events that regulate cellular morphological and functional properties, transcription and cell signaling mechanisms in invasion and metastasis. The provisional matrix that is formed by cancer cells is profoundly different in composition and functions as compared with the matrix of normal tissue. Fibroblasts are mainly responsible for matrix production and remodeling, but in cancer, the tumor matrix in the tumor microenvironment (TME) also originates from cancer cells. Even though extensive research has been conducted on the role of ECM in regulating cancer pathogenesis, its role in modulating OSCC is less elucidated since there are several issues yet to be fully understood. This critical review is focused on recent research as to present and discuss on the involvement of ECM macromolecular effectors (i.e., proteoglycans, integrins, matrix metalloproteinases) in OSCC development and progression.

ANKRD2 expression combined with TNFRSF19 expression for evaluating the prognosis of oral squamous cell carcinoma patients

ObjectiveAs an important chemotherapy drug, cisplatin has been widely used in the treatment of many cancers. However, many patients, including oral squamous cell carcinoma (OSCC) patients, experience unacceptable outcomes from cisplatin treatment. Thus, we devised a risk model for predicting the sensitivity of OSCC patients to cisplatin treatment, to provide a reference for clinical practice. MethodsCAL-27 and SCC-9 cell lines treated or not with cisplatin and data from The Cancer Genome Atlas (TCGA) were screened for simultaneously and significantly differentially expressed genes. Next, we built a risk model for predicting cisplatin sensitivity in OSCC patients. Reverse transcription-polymerase chain reaction (RT-PCR), pathological samples and clinical data were used to examine the reliability of the model. ResultsANKRD2 and TNFRSF19 were differentially expressed between the OSCC metastasis cell line HSC-3 treated and not treated with cisplatin, as well as between the OSCC cell line SCC-25 and the cell line SCC25-DDP, which has cisplatin chemoresistance. We found that the expression of ANKRD2 and TNFRSF19 had a significant influence on the prognosis of OSCC patients. The risk model that combined ANKRD2 and TNFRSF19 to predict sensitivity to cisplatin in OSCC patients was confirmed by analysing the pathological samples and follow-up information of clinical patients. ConclusionsThe expression of ANKRD2 and TNFRSF19 is associated with cisplatin sensitivity and prognosis in patients with OSCC. The survival outcome of patients with oral squamous cell carcinoma (OSCC) was found to be significantly worse in those with high expression of ANKRD2 combined with low expression of TNFRSF19. ANKRD2 and TNFRSF19 may be targets for cisplatin sensitivity prediction in OSCC patients. These findings may provide novel strategies for overcoming cisplatin resistance.

Metabolic Patterns of High-Invasive and Low-Invasive Oral Squamous Cell Carcinoma Cells Using Quantitative Metabolomics and 13C-Glucose Tracing.

Most current metabolomics studies of oral squamous cell carcinoma (OSCC) are mainly focused on identifying potential biomarkers for early screening and diagnosis, while few studies have investigated the metabolic profiles promoting metastasis. In this study, we aimed to explore the altered metabolic pathways associated with metastasis of OSCC. Here, we identified four OSCC cell models (CAL27, HN6, HSC-3, SAS) that possess different invasive heterogeneity via the transwell invasion assay and divided them into high-invasive (HN6, SAS) and low-invasive (CAL27, HSC-3) cells. Quantitative analysis and stable isotope tracing using [U-13C6] glucose were performed to detect the altered metabolites in high-invasive OSCC cells, low-invasive OSCC cells and normal human oral keratinocytes (HOK). The metabolic changes in the high-invasive and low-invasive cells included elevated glycolysis, increased fatty acid metabolism and an impaired TCA cycle compared with HOK. Moreover, pathway analysis demonstrated significant differences in fatty acid biosynthesis; arachidonic acid (AA) metabolism; and glycine, serine and threonine metabolism between the high-invasive and low-invasive cells. Furthermore, the high-invasive cells displayed a significant increase in the percentages of 13C-glycine, 13C-palmitate, 13C-stearic acid, 13C-oleic acid, 13C-AA and estimated FADS1/2 activities compared with the low-invasive cells. Overall, this exploratory study suggested that the metabolic differences related to the metastatic phenotypes of OSCC cells were concentrated in glycine metabolism, de novo fatty acid synthesis and polyunsaturated fatty acid (PUFA) metabolism, providing a comprehensive understanding of the metabolic alterations and a basis for studying related molecular mechanisms in metastatic OSCC cells.

MiR-30a-5p targets ITGA6 to inhibit oral squamous cell carcinoma progression

ObjectiveNowadays, many studies focus on the relationship between microRNAs (miRs) and the development of oral squamous cell carcinoma (OSCC). Here, we broaden the understanding of miR-30a-5p in OSCC. MethodsIn silico analysis was implemented to screen differentially expressed genes in OSCC and the related upstream regulatory miR. OSCC SCC9 cells were manipulated with lentivirus-mediated miR-30a-5p mimic, oe-ITGA6 or sh-ITGA6 and LY294002 (the PI3K/AKT pathway inhibitor) for studying their roles in cell biological processes. Tumors were xenografted in nude mouse for in vivo mechanism verification. ResultsIn silico analysis results depicted that ITGA6 was highly expressed in OSCC, and that miR-30a-5p was the upstream regulatory miR of ITGA6. miR-30a-5p was downregulated and ITGA6 was highly expressed in OSCC tissues and cells. miR-30a-5p targeted and downregulated ITGA6. ITGA6 promoted epithelial-mesenchymal transition, migration and invasion in OSCC cells by activating PI3K/AKT pathway. miR-30a-5p could suppress the in vivo growth and metastasis of OSCC by inhibiting the ITGA6/PI3K/AKT axis. ConclusionTaken together, miR-30a-5p prevents OSCC progression by inhibiting PI3K/AKT pathway through inhibition of ITGA6 expression.

Role of Lymphovascular Invasion in Oral Cavity Squamous Cell Carcinoma Regional Metastasis and Prognosis.

The overall 5-year survival for oral squamous cell carcinoma (OSCC) has not changed in the last 20 years despite advances in treatment. Lymphovascular invasion (LVI) has been shown to be a negative prognostic factor in other cancers, however its role in the prognosis of OSCC remains unclear. This study aims to determine if LVI is a predictor of cervical lymph node metastasis and/or recurrence in OSCC. We conducted a retrospective cohort review of patients from our institutional cancer registry who were treated for OSCC between 2004 and 2018. Patient demographics, surgical pathology results, and clinical outcome data were collected. A multivariable logistic regression analysis was performed to determine if LVI was an independent predictor of cervical lymph node metastasis and/or recurrence. 442 patients were included, 32.8% were female and median age at time of diagnosis was 61.2 years. LVI was present in 32.8% of patients. When controlled for age, sex, t-classification, perineural invasion, depth of invasion (DOI), and margin status, LVI was a significant predictor of the presence of cervical node metastasis (OR: 3.42, CI: 2.17-5.39, P < .001). There was no significant association found between LVI and local recurrence (OR: 1.03, CI: 0.57-1.84, P = .92), regional recurrence (OR: 1.10, CI: 0.57-2.11, P = .78), or distant recurrence (OR: 1.59, CI: 0.87-2.94, P = .13). The results of this study suggest that LVI is a significant predictor of the presence of cervical lymph node metastasis at presentation independent of other known prognostic factors. LVI, however, was not found to be a significant independent predictor of locoregional or distant recurrence.Level of Evidence: Level III.

Multimodal Prediction of Cervical Lymph Node Metastasis and Recurrence in Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma (OSCC) is the most common malignancy in the head/neck region, and cervical lymph node (CLN) metastasis is a strong poor-prognosis factor. In addition, many patients with OSCC experience recurrence despite multidisciplinary treatment. We sought to identify factors associated with CLN metastasis and recurrence in patients with OSCC. We evaluated a total of 45 patients and 233 target CLNs. The longest diameter of the target CLN, the shortest diameter of the target CLN (LS), the area of the target CLN, and the relative computed tomography (CT) values of the target CLNs calculated based on the CT values of the internal jugular vein (LCT) were obtained from preoperative CT images, and the maximum standardized uptake values of the primary tumor (pSUV) and target CLN (nSUV) were obtained from preoperative 18F-fluorodeoxyglucose-positron emission tomography/CT images. We performed immunohistochemical staining for cytokeratin 13 (CK13) and 17 (CK17) on neck dissection tissues. A discrimination equation was used that can predict CLN metastasis with a 92.2% discrimination rate using LS, LCT, pSUV, and nSUV. The CLNs were divided into discrimination and non-discrimination groups based on discriminant equations and CK13 and CK17 were used as the objective variables. A significantly higher recurrence rate was observed in the non-discrimination group (CK13: 5-year recurrence rate 28.6% vs. 64.3%, p<0.01; CK17: 5-year recurrence rate 28.0% vs. 76.0%, p<0.01). CLN metastases in OSCC can be assessed by combining preoperative imaging. The combined use of CK13 and CK17 expression with imaging findings offers an integrated approach to predict OSCC recurrence.

TMEM16A enhances the activity of the Cdc42-NWASP signaling pathway to promote invasion and metastasis in oral squamous cell carcinoma

ObjectiveTo explore the relationship between TMEM16A and metastasis and development in oral squamous cell carcinoma (OSCC). Study DesignDatabases GEPIA and UALCAN were employed to analyze the relationship between the expression of TMEM16A and the survival of oral cancer patients. TMEM16A was knocked down and overexpressed in CAL27 and SCC-4 cells, respectively, and the malignant behavior, and the expression of key proteins were detected. The Cdc42-NWASP pathway was inhibited, and the effects of TMEM16A and Cdc42-NWASP pathway on promoting the malignant behavior of cancer cells were verified. The xenograft tumor model was constructed, and tumor growth, cell proliferation index, apoptosis and Cdc42-NWASP signal pathway activity were detected. ResultsThe expression of TMEM16A in oral cancer tissues was significantly higher than that in adjacent tissues, and the patients with high expression of TMEM16A had shorter survival time. Overexpression of TMTM16A can significantly promote the occurrence of cancer and reduce the apoptosis of cancer cells, while the activity of Cdc42 pathway was higher. Knocking down TMEM16A or inhibiting Cdc42-NWASP pathway can reverse the above results. ConclusionThe activation of Cdc42-NWASP pathway by TMEM16A high expression is closely related to OSCC, which may become a new therapeutic target to prevent OSCC metastasis.

Fibromodulin overexpression drives oral squamous cell carcinoma via activating downstream EGFR signaling

Accumulating evidence has shown that fibromodulin (FMOD) plays a pivotal role in tumorigenesis and metastasis. However, the biological function of FMOD in oral squamous cell carcinoma (OSCC) remains largely unclear to date. In this study, we confirmed that FMOD was overexpressed and showed a significant association with malignant progression and lymph node metastasis in OSCC. Depletion of FMOD inhibited OSCC proliferation and metastasis invitro and invivo. RNA sequencing, western blotting, and rescue assays verified that FMOD exerted oncogenic roles in OSCC via activation of EGFR signaling. In addition, FMOD was proved to be a putative target gene of miR-338-3p. Taken together, FMOD overexpression due to the reduced level of miR-338-3p promotes OSCC by activating EGFR signaling. Our findings provide direct evidence that targeting FMOD could be a promising therapeutic strategy for OSCC patients.

PTP4A1 promotes oral squamous cell carcinoma (OSCC) metastasis through altered mitochondrial metabolic reprogramming

PTP4A1 (Protein tyrosine phosphatase 4A1) is a protein tyrosine phosphatase that regulates a range of pro-oncogenic signaling pathways. Here, we report a novel role for PTP4A1 in oral squamous cell carcinoma (OSCC) growth and development. We show that PTP4A1 is frequently overexpressed in OSCC cells and tissues compared to adjacent non-tumor tissue. In OSCC, the overexpression of PTP4A1 increased cell growth and invasion in vitro, and enhanced tumor progression in vivo. At the molecular level, PTP4A1 was found to regulate mitochondrial metabolic reprogramming to enhance the invasive capacity of OSCC cells. Mechanistically, these effects were mediated through binding to pyruvate kinase isoenzyme M2 (PKM2) to promote its expression and aconitase 2 (ACO2) to enhance its degradation. Together, these data reveal PTP4A1 as a viable target for OSCC therapeutics.

A Bacterial Nanomedicine Combines Photodynamic-Immunotherapy and Chemotherapy for Enhanced Treatment of Oral Squamous Cell Carcinoma.

Bacterial therapy is an emerging hotspot in tumor immunotherapy, which can initiate antitumor immune activation through multiple mechanisms. Porphyromonas gingivalis (Pg), a pathogenic bacterium inhabiting the oral cavity, contains a great deal of pathogen associated molecular patterns that can activate various innate immune cells to promote antitumor immunity. Owing to the presence of protoporphyrin IX (PpIX), Pg is also an excellent photosensitizer for photodynamic therapy (PDT) via the in situ generation of reactive oxygen species. This study reports a bacterial nanomedicine (nmPg) fabricated from Pg through lysozyme degradation, ammonium chloride lysis, and nanoextrusion, which has potent PDT and immune activation performances for oral squamous cell carcinoma (OSCC) treatment. To further promote the tumoricidal efficacy, a commonly used chemotherapeutic drug doxorubicin (DOX) is efficiently encapsulated into nmPg through a simple incubation method. nmPg/DOX thus prepared exhibits significant synergistic effects on inhibiting the growth and metastasis of OSCC both in vitro and in vivo via photodynamic-immunotherapy and chemotherapy. In summary, this work develops a promising bacterial nanomedicine for enhanced treatment of OSCC.

THBS1-Mediated Degradation of Collagen via the PI3K/AKT Pathway Facilitates the Metastasis and Poor Prognosis of OSCC.

Oral squamous cell carcinoma (OSCC) is a prevalent form of malignant tumor, characterized by a persistently high incidence and mortality rate. The extracellular matrix (ECM) plays a crucial role in the initiation, progression, and diverse biological behaviors of OSCC, facilitated by mechanisms such as providing structural support, promoting cell migration and invasion, regulating cell morphology, and modulating signal transduction. This study investigated the involvement of ECM-related genes, particularly THBS1, in the prognosis and cellular behavior of OSCC. The analysis of ECM-related gene data from OSCC samples identified 165 differentially expressed genes forming two clusters with distinct prognostic outcomes. Seventeen ECM-related genes showed a significant correlation with survival. Experimental methods were employed to demonstrate the impact of THBS1 on proliferation, migration, invasion, and ECM degradation in OSCC cells. A risk-prediction model utilizing four differentially prognostic genes demonstrated significant predictive value in overall survival. THBS1 exhibited enrichment of the PI3K/AKT pathway, indicating its potential role in modulating OSCC. In conclusion, this study observed and verified that ECM-related genes, particularly THBS1, have the potential to influence the prognosis, biological behavior, and immunotherapy of OSCC. These findings hold significant implications for enhancing survival outcomes and providing guidance for precise treatment of OSCC.

Predicting cervical lymph node metastasis in OSCC based on computed tomography imaging genomics.

To investigate the correlation between computed tomography (CT) radiomic characteristics and key genes for cervical lymph node metastasis (LNM) in oral squamous cell carcinoma (OSCC). The region of interest was annotated at the edge of the primary tumor on enhanced CT images from 140 patients with OSCC and obtained radiomic features. Ribonucleic acid (RNA) sequencing was performed on pathological sections from 20 patients. the DESeq software package was used to compare differential gene expression between groups. Weighted gene co-expression network analysis was used to construct co-expressed gene modules, and the KEGG and GO databases were used for pathway enrichment analysis of key gene modules. Finally, Pearson correlation coefficients were calculated between key genes of enriched pathways and radiomic features. Four hundred and eighty radiomic features were extracted from enhanced CT images of 140 patients; seven of these correlated significantly with cervical LNM in OSCC (p < 0.01). A total of 3527 differentially expressed RNAs were screened from RNA sequencing data of 20 cases. original_glrlm_RunVariance showed significant positive correlation with most long noncoding RNAs. OSCC cervical LNM is related to the salivary hair bump signaling pathway and biological process. Original_glrlm_RunVariance correlated with LNM and most differentially expressed long noncoding RNAs.