Metastasis Of Squamous Cell Carcinoma Research Articles

68Ga]Ga-FAPI04 Outperforms [18F]FDG PET/CT for Detecting Nodal Metastasis of Head and Neck Squamous Cell Carcinoma: A Single-Center Experience.

This study assesses fibroblast activated protein inhibitor (FAPI) targeted PET/CT imaging against [18F]FDG PET/CT (FDG PET) for detecting nodal involvement in head and neck squamous cell carcinoma (HNSCC), intending to improve diagnostic precision for metastatic lymph nodes and lay the groundwork for future investigations. Methods: Patients diagnosed with HNSCC were retrospectively enrolled. All patients underwent [68Ga]Ga-FAPI04 PET/CT (FAPI PET) and FDG PET within 6 d. Primary tumor, lymph nodes, and tracer uptake were visually and quantitatively compared. The metastatic lymph nodes were evaluated using patient-and lesion-based analyses, with biopsy or postoperative histopathological examination as the reference. Results: The cohort includes 24 patients (17 men, 7 women; mean age 60 ± 11.8 years) who underwent FDG and FAPI PET for preoperative diagnostic workup or restaging due to known recurrence of HNSCC. Lesions included 24 primary tumors, 54 cervical lymph nodes, and 5 metastases. Primary tumors exhibited significant uptake on both PET modalities (median maximum standardized uptake value [SUVmax]: FDG 19.4 ± 11.6, FAPI 16.9 ± 4.6), with no statistically significant difference (p > 0.5). For lymph nodes, FAPI and FDG PET showed median SUVmax of 9.18 ± 6.77 and 9.67 ± 6.5, respectively. The patient-based analysis found FDG PET sensitivity at 88.2% and FAPI PET at 94.1%, with FAPI PET specificity significantly higher (85.7% vs. 42.8% for FDG PET). Lesion-based analysis revealed FAPI PET sensitivity and specificity at 84.2% and 93.7%, respectively, contrasting FDG PET's at 81.5% and 25%, respectively. Conclusion: This study underscores the efficacy of FAPI PET in detecting primary tumors in HNSCC. Furthermore, FAPI PET shows improved specificity over FDG PET for metastatic lymph nodes advocating further investigations for integrating FAPI PET into HNSCC clinical protocols for its enhanced precision in detecting metastatic lymph nodes.

18F-FDG PET/CT Findings of Isolated Renal Metastasis From Squamous Cell Lung Cancer.

We present the 18F-FDG PET/CT findings of a 64-year-old man with isolated renal metastasis. He had a history of radical surgery for squamous cell lung cancer 14 months ago, followed by chemotherapy and immunotherapy. The renal metastasis presented as a small focus of increased FDG uptake in the restaging 18F-FDG PET/CT scan, which was regarded as renal cortical tracer retention. The renal metastasis was more prominent on the second PET/CT performed 5 months later. The patient subsequently underwent radical nephrectomy, and histopathological examination confirmed the diagnosis of renal squamous cell carcinoma metastasis.

Lymph node metastasis determined miRNAs in esophageal squamous cell carcinoma.

There is no golden noninvasive and effective technique to diagnose lymph node metastasis (LNM) for esophageal squamous cell carcinoma (ESCC) patients. Here, a classifier was proposed consisting of miRNAs to screen ESCC patients with LNM from the ones without LNM. miRNA expression and clinical data files of 93 ESCC samples were downloaded from TCGA as the discovery set and 119 ESCC samples with similar dataset GSE43732 as the validation set. Differentially expressed miRNAs (DE-miRNAs) were analyzed between patients with LNM and without LNM. LASSO regression was performed for selecting the DE-miRNA pair to consist the classifier. To validate the accuracy and reliability of the classifier, the SVM and AdaBoost algorithms were applied. The CCK-8 and wound healing assay were used to evaluate the role of the miRNA in ESCC cells. There were 43 DE miRNAs between the LNM+ group and LNM- group. Among them, miR-224-5p, miR-99a-5p, miR-100-5p, miR-34c-5p, miR-503-5p, and miR-452-5p were identified by LASSO to establish the classifier. SVM and AdaBoost showed that the model could classify the ESCC patients with LNM from the ones without LNM precisely and reliably in 2 data sets. miR-224-5p in the classifier as the top contributor to discriminate the two groups of patients based on AdaBoost, promoted ESCC cell proliferation and migration in vitro. The classifier based on these 6 miRNAs could classify the ESCC patients with LNM from the ones without LNM successfully.

Therapeutic and Diagnostic Tactics for Metastases to the Lymph Nodes of the Neck without an Identified Primary Focus

Introduction. Metastatic squamous cell carcinoma from an unknown primary focus accounts for less than 5 % of malignant tumors in the head and neck. Improving the methods of diagnosis can reduce the incidence of this pathology. Materials and methods. A retrospective analysis of the results of diagnosis and treatment of 59 patients with metastasis to the lymph nodes of the neck without an identified primary focus was performed. The proportion of male patients was 86 % (51/59), female — 14 % (8/59). The average age of patients is 61 years. Squamous cell carcinoma prevailed — 79 % (47/59). Results. Metastatically affected lymph nodes were localized in 92 % of cases at levels II and III. The proportion of patients with stages N2, N3 prevailed — 55 % (abs. 26), 32 % (abs. 15), respectively. Overexpression of the P­16 protein in metastatically affected lymph nodes was detected in 70 %, PD­L1 in 48 %, and Epstein­Barr virus (EBV) in 6 %. Ipsilateral diagnostic palatine tonsillectomy of an apparently unchanged tonsil was performed in 15 % (9/59) of cases, revealing the primary site in one instance. Of the special treatment methods, complex and combined treatment prevailed — 55 % (abs. 26). Radiation therapy in an independent version was performed by 48 % of patients, while 76 % received the full course (abs. 16). Combined treatment (a course of Radiation therapy followed by chemotherapy) — in 7 % (abs. 3) 20 % of patients received polychemotherapy. Palliative immunotherapy (pembrolizumab 200 mg IV — 5 courses) was given to 1 patient. The average life expectancy was higher with complex treatment — it was 60 months (95 % CI 43.5–76.4), the median survival is 60 months. Discussion. The main methods of treatment of patients with metastases of squamous cell carcinoma without were radiation therapy in an independent version, as well as complex treatment. Ipsilateral diagnostic palatine tonsillectomy of an apparently unchanged tonsil was performed in 15 % (abs. 9), and allowed to identify the primary focus in 1 case.Conclusion. Metastasis to the lymph nodes of the neck without remains an urgent interdisciplinary problem. Prospective multicenter studies are required to improve and optimize the algorithms for diagnosis and treatment of these patients.

Single cell analysis revealed SFRP2 cancer associated fibroblasts drive tumorigenesis in head and neck squamous cell carcinoma

Understanding the mechanisms of invasion and metastasis in head and neck squamous cell carcinoma (HNSCC) is crucial for effective treatment, particularly in metastatic cases. In this study, we analyzed multicenter bulk sequencing and comprehensive single-cell data from 702,446 cells, leading to the identification of a novel subtype of cancer-associated fibroblasts (CAFs), termed Secreted Frizzled-Related Protein2 CAFs (SFRP2_CAFs). These cells, originating from smooth muscle cells, display unique characteristics resembling both myofibroblastic CAFs and inflammatory CAFs, and are linked to poorer survival outcomes in HNSCC patients. Our findings reveal significant interactions between SFRP2_CAFs and SPP1 tumor-associated macrophages, which facilitate tumor invasion and metastasis. Moreover, our research identifies Nuclear factor I/X (NFIX) as a key transcription factor regulating SFRP2_CAFs behavior, confirmed through gene regulatory network analysis and simulation perturbation.

The combination of p16 and Rb expression pattern is helpful to predict high-risk HPV infection and the primary site in lymph node metastases of squamous cell carcinoma

Identifying the primary site of metastatic squamous cell carcinoma in lymph nodes can be challenging. An immunohistochemistry (IHC) analysis recently revealed that high-risk human papillomavirus (HR-HPV)-associated oropharyngeal squamous cell carcinomas (OPSCCs) typically show overexpression of p16 protein and a partial loss pattern of Rb. Nevertheless, the status of these markers in metastatic lesions is still unclear. In this study, we examined p16 and Rb expression status by IHC and transcriptionally active HR-HPV infection by mRNA in situ hybridization in paired primary and metastatic SCC lesions. A total of 50 patients with OPSCCs (n=17), hypopharyngeal SCCs (n=16), laryngeal SCCs (n=6), or uterine cervical SCCs (n=11) were enrolled. HR-HPV and p16 were positive in 21/50 (42 %) and 23/50 (46 %) patients, respectively. Primary and metastatic lesions showed concordant results for those three markers in individual patients. Among the p16-positive patients (n=23), HPV-positive cases typically showed a partial loss of Rb (n=20) and, rarely, a complete loss of Rb (n=1), whereas HPV-negative cases showed preserved Rb expression (n=2). All 27 p16-negative cases lacked HPV infection, while preserved expression and complete loss of Rb were observed in 26 and 1 of the p16-negative cases, respectively. Compared to standalone p16, the combination of p16 overexpression and Rb-partial/complete loss showed equally excellent sensitivity and negative predictive value (each 100 %) as well as improved specificity (100 % versus 93.1 %) and positive predictive value (100 % versus 91.3 %). Our results suggest that combining p16 and Rb expression patterns may be helpful in screening for HR-HPV infection in metastatic lymph nodes and in estimating the primary site of SCC.

Supraclavicular lymph node metastasis should not be defined as regional lymph node metastasis in cervical and upper thoracic esophageal squamous cell carcinoma.

The importance of supraclavicular lymph node (SCLN) metastasis in cervical and upper thoracic esophageal squamous cell carcinoma (ESCC) has not been determined. The aim of the present study was to provide a detailed definition of the range of SCLN regions and to explore whether SCLNs should be considered as a regional lymph nodes for patients with cervical and upper thoracic ESCC. A retrospective analysis was performed on 230 patients with locally advanced cervical or upper thoracic ESCC who underwent radical radiotherapy and chemotherapy. The range of SCLN regions was defined in detail on contrast enhanced computed tomography images of the neck. According to whether the patient had lymph node metastasis in the supraclavicular region, the included patients were divided into two groups, and the survival differences and reasons for treatment failure between the two groups were analyzed. Of the 230 patients with ESCC, 71 (30.87%) exhibited lymph node metastases in the supraclavicular region. The median overall survival time of ESCC patients with and without SCLN metastasis was 17 and 30 months, respectively (P<0.001). After propensity score matching (PSM), the median overall survival time of ESCC patients with and without SCLN metastasis was 17 and 28 months, respectively (P<0.001). During the follow-up period, there were a total of 101 cases of failure of treatment in the irradiation field, 6 cases had esophageal metastasis in the non-irradiated field and 27 cases had regional lymph node metastasis in the non-irradiated field. In addition, there were 33 cases of metastasis to the distant lymph nodes or organs. There was no significant difference in the local treatment failure rate between the groups with or without SCLN metastasis in both the irradiation field and the non-irradiation field, but the probability of distant metastasis in the SCLN metastasis group was significantly higher than that in the group without SCLN metastasis (P=0.025). In conclusion, patients with cervical and upper thoracic ESCC with SCLN metastasis have a poor prognosis and the median overall survival time is closer to that of metastatic ESCC than ESCC with regional lymph node metastasis; therefore, SCLNs should not be defined as regional lymph nodes in patients with cervical and upper thoracic ESCC.

LNMAC Promotes Cervical Squamous Cell Carcinoma Lymphatic Metastasis via Epigenetic Regulation of FGF2-Induced Lymphangiogenesis.

The lymph node is the most common site of distant metastasis of cervical squamous cell carcinoma (CSCC), which elicits dismal prognosis and limited efficiency for treatment. Elucidation of the mechanisms underlying CSCC lymphatic metastasis would provide potential therapeutic strategies for nodal metastatic of CSCC. Here, based on in vivo lymphatic metastasis screening model, a circular RNA is identified that is termed as lymph node metastasis associated circRNA (LNMAC), is markedly upregulated in lymphatic metastatic CSCC and correlated with lymph node metastasis. Overexpression of LNMAC dramatically augments the metastatic capability of CSCC cells to the lymph node via inducing lymphangiogenesis. Mechanistically, LNMAC epigenetically upregulates fibroblast growth factor 2 (FGF2) expression by directly associating with histone acacetylase 1 (HDAC1), preventing Importin α6/8-mediated nuclear translocation of HDAC1 and eliciting histone H3K27ac-induced FGF2 transcriptional activation. Treatment with 3F12E7, an anti-FGF2 monoclonal antibody, effectively inhibits LNMAC-induced CSCC lymphatic metastasis. Taken together, these findings indicate that LNMAC plays a crucial role in FGF2-mediated lymphangiogenesis and lymphatic metastasis, highlighting that LNMAC might be a therapeutic target for lymph node metastasis in CSCC patients.

Upregulation of LY6K induced by FTO-mediated demethylation promotes the tumorigenesis and metastasis of oral squamous cell carcinoma via CAV-1-mediated ERK1/2 signaling activation.

Lymphocyte antigen 6 complex locus K (LY6K) has been demonstrated to play a significant role in cancers and identified as a therapeutic biomarker for head and neck squamous cell carcinoma. However, the role of LY6K in oral squamous cell carcinoma (OSCC) has not been explored. The current study discovered that LY6K was aberrantly upregulated in OSCC cell lines and tissues and that high LY6K expression significantly correlated with poorer survival of OSCC patients. Through stable knockdown of LY6K, we found that the growth, colony formation, migration, and invasion of OSCC cells were substantially suppressed. In addition, tumor growth and lung metastasis in vivo were effectively inhibited by LY6K depletion. Mechanically, LY6K binds with CAV-1 and activates CAV-1-mediated MAPK/ERK signaling to exert its oncogenic effects on OSCC. In addition, LY6K expression in OSCC was discovered to be regulated by FTO-mediated RNA N6-methyladenosine (m6A) modification in an IGF2BP1-dependent manner. Generally, LY6K expression was upregulated by FTO-mediated demethylation in OSCC, which promoted the tumorigenesis and metastasis of OSCC via activating the CAV-1-mediated ERK1/2 signaling pathway.

MiRNA-199b-5p suppresses of oral squamous cell carcinoma by targeting apical-basolateral polarity via Scribble/Lgl

In epithelial cells, Scribble forms cell-cell junctions and contribute to cell morphology and homeostasis by regulating apical-basolateral polarity in mammals and functions as a tumor suppressor in many carcinomas. The initial diagnosis of oral squamous cell carcinoma is important, and its prognosis is poor when accompanied by metastasis. However, research on the mechanisms of oral squamous cell carcinoma metastasis is insufficient. Herein, we showed that Scribble regulates the apical-basolateral polarity of oral squamous cell carcinoma by regulating lethal giant larvae 1, Scribble module and E-cadherin, the adhesion junction. The expression of lethal giant larvae 1 and E-cadherin decreased when the expression of Scribble was knocked down and their localization was completely disrupted in both the oral squamous cell carcinoma cell line and in vivo model. In particular, the Scribble was involved in oral squamous cell carcinoma metastasis via hsa-miR-199b-5p, which is a microenvironmental factor of hypoxia. The disruption of Scribble localization under hypoxic conditions, but its localization was maintained in miR-199b-5p oral squamous cell carcinoma cell lines and in vivo. These results suggest that Scribble functions as a tumor suppressor marker mediated by miR-199b-5p in oral squamous cell carcinoma.

LncOCMRL1 promotes oral squamous cell carcinoma growth and metastasis via the RRM2/EMT pathway

BackgroundLong noncoding RNAs (lncRNAs) are widely involved in cancer development and progression, but the functions of most lncRNAs have not yet been elucidated. Metastasis is the main factor restricting the therapeutic outcomes of various cancer types, including oral squamous cell carcinoma (OSCC). Therefore, exploring the key lncRNAs that regulate OSCC metastasis and elucidating their molecular mechanisms will facilitate the development of new strategies for effective OSCC therapy.MethodsWe analyzed the lncRNA expression profiles of tumor tissues from OSCC patients with and without cervical lymph node metastasis, and OSCC cell lines. We revealed high expression of oral squamous cell carcinoma metastasis-related lncRNA 1 (lncOCMRL1) in OSCC patient tumor tissues with lymph node metastasis and highly metastatic OSCC cell lines. The effects of lncOCMRL1 knockdown on the invasion, migration and proliferation abilities of OSCC cells were explored through qRT-PCR, Transwell, colony formation, and cell proliferation experiments. The mechanism by which lncOCMRL1 promotes OSCC metastasis and proliferation was explored through RNA pull-down, silver staining, mass spectrometry, RIP, and WB experiments. To increase its translational potential, we developed a reduction-responsive nanodelivery system to deliver siRNA for antitumor therapy.ResultsWe determined that lncOCMRL1 is highly expressed in OSCC metastatic tumor tissues and cells. Functional studies have shown that high lncOCMRL1 expression can promote the growth and metastasis of OSCC cells both in vivo and in vitro. Mechanistically, lncOCMRL1 could induce epithelial-mesenchymal transition (EMT) via the suppression of RRM2 ubiquitination and thereby promote the proliferation, invasion, and migration of OSCC cells. We further constructed reduction-responsive nanoparticles (NPs) for the systemic delivery of siRNAs targeting lncOCMRL1 and demonstrated their high efficacy in silencing lncOCMRL1 expression in vivo and significantly inhibited OSCC tumor growth and metastasis.ConclusionsOur results suggest that lncOCMRL1 is a reliable target for blocking lymph node metastasis in OSCC.

Preoperative dual-energy computed tomography and positron-emission tomography evaluation of lymph node metastasis in esophageal squamous cell carcinoma

Preoperative dual-energy computed tomography and positron-emission tomography evaluation of lymph node metastasis in esophageal squamous cell carcinoma

Neoteric Predictors for Lymph Node Metastasis in Early Oral Squamous Cell Carcinoma: Tumor Budding and Worst Pattern of Invasion

Neoteric Predictors for Lymph Node Metastasis in Early Oral Squamous Cell Carcinoma: Tumor Budding and Worst Pattern of Invasion

Development and validation of a CT-based deep learning radiomics signature to predict lymph node metastasis in oropharyngeal squamous cell carcinoma: a multicenter study.

Lymph node metastasis (LNM) is a pivotal determinant that influences the treatment strategies and prognosis for oropharyngeal squamous cell carcinoma (OPSCC) patients. This study aims to establish and verify a deep learning (DL) radiomics model for the prediction of LNM in OPSCCs using contrast-enhanced computed tomography (CECT). A retrospective analysis included 279 OPSCC patients from three institutions. CECT images were used for handcrafted (HCR) and DL feature extraction. Dimensionality reduction for HCR features used recursive feature elimination and least absolute shrinkage and selection operator algorithms, whereas DL feature dimensionality reduction used variance-threshold and recursive feature elimination algorithms. Radiomics signatures were constructed using support vector machine, decision tree, random forest, k-nearest neighbor, gaussian naive bayes classifiers and light gradient boosting machine. A combined model was then constructed using the screened DL, HCR, and clinical features. The area under the receiver operating characteristic curve (AUC) served to quantify the model's performance, and calibration curves were utilized to assess its calibration. The combined model exhibited robust performance, achieving AUC values of 0.909 (95% CI: 0.861-0.957) in the training cohort, 0.884 (95% CI: 0.800-0.968) in the internal validation cohort, and 0.865 (95% CI: 0.791-0.939) in the external validation cohort. It outperformed both the clinical model and best-performing radiomics model. Moreover, calibration was deemed satisfactory. The combined model based on CECT demonstrates the potential to predict LNM in OPSCCs preoperatively, offering a valuable tool for more precise and tailored treatment strategies. This study presents a novel combined model integrating clinical factors with deep learning radiomics, significantly enhancing preoperative LNM prediction in OPSCC.

Dysregulation of a novel m6A regulator YWHAG is correlated with metastasis and poor prognosis in oral squamous cell carcinoma – A cross-sectional study

ObjectiveThis study aimed to investigate the role of a novel m6A and cell cycle regulator YWHAG in oral squamous cell carcinoma (OSCC) by analyzing its expression and functional implications. DesignTumor samples (n = 51) and adjacent non-tumor samples (n = 38) were collected from patients with OSCC, and cell lines were processed. YWHAG mRNA expression was assessed using quantitative reverse transcription PCR (RT-qPCR) analysis. Various tools, such as UALCAN, Protein-Atlas analysis, TIMER 2.0, and other in silico tools, were used to explore clinicopathological correlations, protein expression, immune cell infiltration, and functional associations of YWHAG. ResultsYWHAG mRNA and protein expression were significantly upregulated in OSCC tumor tissues and OSCC cell lines compared to non-tumor tissues and normal cells (p < 0.001). High YWHAG expression significantly correlated with advanced tumor stage, higher grade, lymph node metastasis, and poor prognosis (p < 0.05). Functional analysis revealed that YWHAG is associated with pathways involved in aggressive cancer progression. YWHAG expression positively correlated with its target gene CTTN expression, which was also upregulated in OSCC and associated with poor prognosis (p < 0.05). ConclusionsStudy findings indicate that YWHAG may contribute to the progression of OSCC and could be a potential therapeutic target or prognostic biomarker. Further investigation is necessary to understand the underlying mechanisms and assess the clinical implications of YWHAG dysregulation in OSCC.

A case controlled study of risk factors for metastatic squamous cell carcinoma in organ transplant recipients: single academic medical center.

Solid organ transplant recipients (SOTRs) are at high risk of cutaneous squamous cell carcinoma (cSCC) metastasis. Despite prior studies identifying risk factors, mortality remains high. Understanding additional risk factors may aid in reducing mortality in this population. This study aimed to investigate risk factors and predictive variables for metastatic cSCC in SOTRs. The primary goal was to accurately identify transplant patients at increased risk of metastatic cSCC. A retrospective case-control study in a single institution of 3576 cases of organ transplants were identified from January 1991 to July 2022. A cohort of metastatic cancer patients and two randomly generated age and organ matched control cohorts were identified. 16 SOTR patients developed metastatic cSCC. The majority were male, with high-risk tumor sites. Tumor depth varied and half exhibited perineural invasion. Cylex® (p = 0.05) and white blood cell counts (p = 0.04) were significantly lower in these patients compared to control. Lung transplants were at highest risk relative to other solid organ transplants. Voriconazole exposure was also associated with increased metastatic risk (p = 0.04). Small sample size at a single institution. Close monitoring of SOTR, especially those with lung transplants given their increased risk, reducing immunosuppression, and limiting exposure to voriconazole can improve outcomes in SOTRs with metastatic cSCC.

Nodal Metastasis in Oral Squamous Cell Carcinoma: an Analysis of Risk Factors and Influence on Overall Survival

Introduction: Oral squamous cell carcinoma (OSCC) presents a high tendency of lymph node metastasis (LNM). Objective: Determine which risk factors play a significant role in metastasis to cervical lymph nodes and to evaluate the influence of nodal involvement on overall survival of patients with OSCC. Method: Medical records of 350 patients with OSCC were retrospectively reviewed. The data were analyzed using the chi-square, Fisher’s exact and log-rank Mantel Cox tests and multinomial and Cox logistic regression. Results: Of the 350 medical records evaluated, 251 reported N0, 75 N1, 16 N2 and 8 N3. Male gender, referrals from private health care providers, T3/4 stage and non-surgical treatments were associated with LNM. In multivariate analysis, men and T3/4 tumors were shown to be independent risk factors for LNM. The independent risk factors for survival were male gender, nodal involvement (p = 0.017) and non-surgical treatment. Conclusion: Male gender and T-stage are risk factors for LNM in patients with OSCC. Moreover, the presence of LNM and age &gt;65 years are associated with poor overall survival.urvivor.

Long non-coding RNA MAGEA4-AS1 binding to p53 enhances MK2 signaling pathway and promotes the proliferation and metastasis of oral squamous cell carcinoma

Long non-coding RNAs (lncRNAs) regulate the occurrence, development and progression of oral squamous cell carcinoma (OSCC). We elucidated the expression features of MAGEA4-AS1 in patients with OSCC and its activity as an OSCC biomarker. Furthermore, the impact of up-regulation of MAGEA4-AS1 on the cellular behaviors (proliferation, migration and invasion) of OSCC cells and intrinsic signal mechanisms were evaluated. Firstly, we analyzed MAGEA4-AS1 expression data in The Cancer Genome Atlas (TCGA) OSCC using a bioinformatics approach and in 45 pairs of OSCC tissues using qPCR. Then CCK-8, ethynyl deoxyuridine, colony formation, transwell and wound healing assays were conducted to assess changes in the cell proliferation, migration and invasion protential of shMAGEA4-AS1 HSC3 and CAL27 cells. The RNA sequence of MAGEA4-AS1 was identified using the rapid amplification of cDNA ends (RACE) assay. And whole-transcriptome sequencing was used to identify MAGEA4-AS1 affected genes. Additionally, dual-luciferase reporter system, RNA-binding protein immunoprecipitation (RIP), and rescue experiments were performed to clarify the role of the MAGEA4-AS1-p53-MK2 signaling pathway. As results, we found MAGEA4-AS1 was up-regulated in OSCC tissues. We identified a 418 nucleotides length of the MAGEA4-AS1 transcript and it primarily located in the cell nucleus. MAGEA4-AS1 stable knockdown weakened the proliferation, migration and invasion abilities of OSCC cells. Mechanistically, p53 protein was capable to activate MK2 gene transcription. RIP assay revealed an interaction between p53 and MAGEA4-AS1. MK2 up-regulation in MAGEA4-AS1 down-regulated OSCC cells restored MK2 and epithelial-to-mesenchymal transition related proteins’ expression levels. In conclusion, MAGEA4-AS1-p53 complexes bind to MK2 promoter, enhancing the transcription of MK2 and activating the downstream signaling pathways, consequently promoting the proliferation and metastasis of OSCC cells. MAGEA4-AS1 may serve as a diagnostic marker and therapeutic target for OSCC patients.

Risk factors and impact of occult and skip metastasis in early-stage oral tongue squamous cell carcinoma.

To investigate risk factors associated with occult lymph node metastases (ONM) and skip metastasis in early-stage oral tongue squamous cell carcinoma (OTSCC) patients. Meanwhile, to analyze the contribution of metastatic nodes to survival outcomes. 544 OTSCC patients who were clinically staged T1-T2N0 with pathologic results from May 2018 to January 2024 were enrolled. Those with ONM were divided into subgroups with or without skip metastasis. Clinical, laboratorial, radiological and pathological factors between groups were analyzed by using univariate analysis and multivariate logistic analysis. The association of tumor growth behavior with the metastatic pattern of lymph nodes was summarized. Additionally, disease free survival (DFS) among different groups were compared using Kaplan-Meier analysis. Tumor growth behavior was associated with ONM. Tumor thickness with a threshold of 6.4mm was not inferior to histological depth of invasion in predicting ONM. Only 1.3% of patients had nodal involvement of neck level IV or V. The DFS of patients with ONM were significantly reduced than those without ONM (P<0.001). The DFS between patients with and without skip metastasis exhibited no statistical significance(P = 0.246). The 1-year, 2-year recurrence rates of patients with or without ONM were 31.9%, 37.5%, 10.1% and 14.0%, correspondingly. Tumor thickness with a threshold of 6.4mm could be used as a preoperative predictor for ONM. Elective neck dissection of level I - III might be sufficient for early stage OTSCC patients. OTSCC patients with ONM should be closely observed during the first 2 years after surgery. The risk of ONM in early stage OTSCC patients might be predicted by tumor thickness calculated on MR imaging. Elective neck dissection of level I - III could remove micrometastases timely and effectively.

Abnormal p53 Immunohistochemical Patterns Are Associated with Regional Lymph Node Metastasis in Oral Cavity Squamous Cell Carcinoma at Time of Surgery

Most (60%-80%) of the oral cavity invasive squamous cell carcinoma (OSCC) demonstrate molecular alterations in TP53. The presence of TP53 mutations in multiple organ systems has been associated with a more aggressive clinical course. This study aimed to classify OSCC into p53 wild-type OSCC and p53-abnormal OSCC using p53 immunohistochemistry and to determine if abnormal p53 status correlates with a higher risk of lymph node metastasis at the time of surgery. A total of 101 patients with OSCC resection and cervical lymph node dissection were identified. p53 immunohistochemistry was performed for all cases and scored into p53 wild-type (p53-HPV: midepithelial/basal sparing, markedly reduced [null-like]/basal sparing; p53-conventional: scattered basal, patchy basal/parabasal) and p53-abnormal (overexpression basal/parabasal only, overexpression basal/parabasal to diffuse, null, and cytoplasmic) patterns. p16 immunohistochemistry and high-risk HPV RNA in situ hybridization were used to confirm the HPV status in cases showing midepithelial/basal sparing or markedly reduced (null-like)/basal sparing pattern. Logistic regression analysis was performed to investigate the association of p53 status, tumor size, depth of invasion, and pT stage against lymph node status. We identified 22 cases with p53 wild-type patterns (16 p53-conventional, 6 p53-HPV) and 79 cases with p53-abnormal patterns. Two of 22 p53 wild-type cases had positive lymph nodes (1 p53-conventional, 1 p53-HPV), whereas 40 of 79 p53-abnormal cases had positive lymph nodes (P < .001). Multivariate analysis showed that p53-abnormal pattern was an independent risk factor associated with positive node(s) with an odds ratio of 8.12 (95% CI, 2.10-53.78; P = .008).p53-Abnormal OSCCs were significantly more likely to be associated with positive lymph node status than p53 wild-type OSCCs at the time of surgery. Further investigation with long-term follow-up is required to determine its clinical application before surgery planning.