Metastasis Of Squamous Cell Carcinoma Research Articles

C-Myc-dependent LAMP3 regulates the proliferation, metastasis and metabolic reprogramming of tongue squamous cell carcinoma

To delve into the role and molecular mechanism of lysosome-associated membrane protein 3 (LAMP3) in tongue squamous cell carcinoma (TSCC). Differential expression of LAMP3 in TSCC from GEO microarray was analyzed, and pathway enrichment analysis of LAMP3 was performed utilizing GSEA. LAMP3 expression was detected by western blot, immumohistochemical staining and qRT-PCR. LAMP3 knockdown plasmid was constructed for a variety of biological function assays to verify the involvement of LAMP3 in TSCC. The upstream transcription factors and binding sites of LAMP3 were bioinformatically predicted. Dual luciferase reporter gene assay was applied to check the presence of c-Myc binding to the promoter region of LAMP3 and the regulation of its transcription. Further, a xenograft tumor model was developed to corroborate the impact of LAMP3 on tumor growth in vivo. LAMP3 expression was enhanced in TSCC tissues and cells. LAMP3 knockdown attenuated TSCC cell proliferation, DNA replication and metastatic capacity while induced glucose metabolism reprogramming in vitro. Meanwhile, LAMP3 depletion contributed to the delay of tumor progression in vivo. c-Myc was found bind to the LAMP3 promoter region to positively modulate LAMP3 transcriptional expression. LAMP3 regulated by c-Myc enhanced TSCC cell proliferation, DNA replication capacity while induced glucose metabolism reprogramming, suggesting a potential target for clinical trials in TSCC.

Assessing the value of artificial intelligence-based image analysis for pre-operative surgical planning of neck dissections and iENE detection in head and neck cancer patients

ObjectivesAccurate preoperative detection and analysis of lymph node metastasis (LNM) in head and neck squamous cell carcinoma (HNSCC) is essential for the surgical planning and execution of a neck dissection and may directly affect the morbidity and prognosis of patients. Additionally, predicting extranodal extension (ENE) using pre-operative imaging could be particularly valuable in oropharyngeal HPV-positive squamous cell carcinoma, enabling more accurate patient counseling, allowing the decision to favor primary chemoradiotherapy over immediate neck dissection when appropriate. Currently, radiological images are evaluated by radiologists and head and neck oncologists; and automated image interpretation is not part of the current standard of care. Therefore, the value of preoperative image recognition by artificial intelligence (AI) with the large language model (LLM) ChatGPT-4 V was evaluated in this exploratory study based on neck computed tomography (CT) images of HNSCC patients with cervical LNM, and corresponding images without LNM. The objective of this study was to firstly assess the preoperative rater accuracy by comparing clinician assessments of imaging-detected extranodal extension (iENE) and the extent of neck dissection to AI predictions, and secondly to evaluate the pathology-based accuracy by comparing AI predictions to final histopathological outcomes. Materials and methods45 preoperative CT scans were retrospectively analyzed in this study: 15 cases in which a selective neck dissection (sND) was performed, 15 cases with ensuing radical neck dissection (mrND), and 15 cases without LNM (sND). Of note, image analysis was based on three single images provided to both ChatGPT-4 V and the head and neck surgeons as reviewers. Final pathological characteristics were available in all cases as HNSCC patients had undergone surgery. ChatGPT-4 V was tasked with providing the extent of LNM in the preoperative CT scans and with providing a recommendation for the extent of neck dissection and the detection of iENE. The diagnostic performance of ChatGPT-4 V was reviewed independently by two head and neck surgeons with its accuracy, sensitivity, and specificity being assessed.ResultsIn this study, ChatGPT-4 V reached a sensitivity of 100% and a specificity of 34.09% in identifying the need for a radical neck dissection based on neck CT images. The sensitivity and specificity of detecting iENE was 100% and 34.15%, respectively. Both human reviewers achieved higher specificity. Notably, ChatGPT-4 V also recommended a mrND and detected iENE on CT images without any cervical LNM.DiscussionIn this exploratory study of 45 preoperative CT Neck scans before a neck dissection, ChatGPT-4 V substantially overestimated the degree and severity of lymph node metastasis in head and neck cancer. While these results suggest that ChatGPT-4 V may not yet be a tool providing added value for surgical planning in head and neck cancer, the unparalleled speed of analysis and well-founded reasoning provided suggests that AI tools may provide added value in the future.

High Kin17 expression is correlated with metastasis and prognosis of esophageal squamous cell carcinoma.

BackgroundKin17 is critical in regulating the proliferation and metastasis of tumors in various malignancies. However, the relationship between Kin17 expression, clinicopathologic features, and esophageal squamous cell carcinoma (ESCC) prognosis remains unclear.MethodsThe analysis of Kin17 messenger RNA (mRNA) expression involved the utilization of data from The Cancer Genome Atlas (TCGA) dataset through the platforms the University of ALabama at Birmingham CANcer data analysis portal (UALCAN) and the Gene Expression Omnibus (GEO). To determine the expression levels of Kin17 in tissues, immunohistochemistry was conducted. Using Pearson's chi-square test, the relationship between Kin17 expression and clinicopathological variables was evaluated. Cox proportional hazard models (both univariate and multivariate), receiver operating characteristic (ROC) curves, and Kaplan-Meier survival curves were used to analyze survival.ResultsIn both the TCGA and GEO datasets, the mRNA level of Kin17 was greater in tumor tissues when compared to tumor-adjacent tissues (P < 0.001). Similarly, there was a significant expression of Kin17 (P < 0.0001) in ESCC tissues. Elevated Kin17 expression correlated significantly with increased Ki-67 levels (P < 0.001), advanced pathological tumor node metastasis stage (P = 0.01), and positive lymph node metastasis (P = 0.02). According to univariate and multivariate Cox models, high Kin17 expression was associated with poorer progression-free survival (PFS) (hazard ratio (HR): 1.990, 95% confidence interval (CI): (1.040-3.810)), and Kin17 was an independent prognostic variable for overall survival (OS) (HR: 2.321, 95% CI: (1.056-5.101)). ROC curve showed that the area under the curve for predicting PFS and OS using the combination of Kin17 and K-i67 was 0.7088 and 0.7031, respectively. High Kin17 expression was associated with unfavorable PFS (HR: 2.009, 95% CI: (1.059-3.811)) and OS (HR: 2.997, 95% CI: (1.488-6.040)).ConclusionsKin17 is abundantly expressed in ESCC tissues and is potentially useful for prognostic evaluation and as a target for therapeutic interventions in ESCC.

MCTP2 is a novel biomarker promoting tumor progression and nodal metastasis in oral squamous cell carcinoma

Head and neck cancer is the sixth most common cancer worldwide. Among them, oral squamous cell carcinoma (OSCC) has remarkable local invasiveness and lymph node metastasis and is frequently found at an advanced stage. The 5-year survival rate of OSCC has remained at approximately 50% for several decades, and there is an urgent need to identify molecular markers that are effective for early diagnosis and treatment. Multiple C2 transmembrane proteins (MCTPs) are C2 domain-containing proteins, with two subtypes in humans: MCTP1 and MCTP2. MCTP1 has been reported to exhibit tumor-promoting activity in several cancer types; however, the role of MCTP2 in cancer remains largely unknown. In this study, we performed a comprehensive analysis using big data from over 500 head and neck cancer cases registered in The Cancer Genome Atlas (TCGA), expression profiling of 63 OSCC samples, and in vitro functional assessment using cell lines to elucidate MCTP2 involvement in OSCC. Compared to normal oral mucosa, MCTP2 expression was elevated in OSCC, and its expression rate was significantly increased at both protein and mRNA levels in cases with lymph node metastasis. In vitro experiments using two OSCC cell lines demonstrated that MCTP2 may be involved in cancer cell migration, invasive capacity acquisition, and epithelial-mesenchymal transition (EMT) phenotype. Furthermore, MCTP2 expression levels were upregulated by TGF-β1 in a concentration-dependent manner. These findings suggest that MCTP2 may serve as a novel marker of invasion and EMT in OSCC, with promising implications for developing new MCTP2-targeted diagnostic and therapeutic approaches for OSCC.

Conventional ultrasound and contrast-enhanced ultrasound for predicting cervical lymph node metastasis in head and neck squamous cell carcinoma

Objective: To evaluate the diagnostic efficacy of conventional ultrasound combined with contrast-enhanced ultrasound (CEUS) for detecting cervical lymph node metastasis in head and neck squamous cell carcinoma (HNSCC). Methods: This retrospective case control study included 259 patients (249 males and 10 females,aged 40-88 years with a median age of 63 years) who were pathologically diagnosed with HNSCC at the First Affiliated Hospital of Chongqing Medical University from April 2022 to August 2024. A total of 259 lymph nodes were assessed(78 pathologically positive nodes and 181 pathologically negative ones). Receiver operating characteristic (ROC) curves were plotted to compare the diagnostic efficacies of conventional ultrasound combined with CEUS and CT, MRI, or conventional ultrasound for cervical lymph node metastasis. Patients were randomly assigned to a training group (n=208) and a validation group (n=51) (8∶2). Univariate and multivariate Logistic regression were used to analyze the independent risk factors for lymph node metastasis prediction. A nomogram model was constructed based on independent risk factors. The model predictive efficacy was assessed by ROC curve, and model's fit was evaluated by Hosmer-Lemeshow test. Results: The area under the curve (AUC) for conventional ultrasound combined with CEUS in predicting cervical lymph node metastasis in HNSCC was 0.923 (95%CI: 0.880-0.965), which was significantly higher than those for enhanced CT, cervical enhanced MRI, and conventional ultrasound [AUC were 0.820 (95%CI: 0.753-0.886), 0.802 (95%CI: 0.737-0.866), and0.836 (95%CI: 0.774-0.899), respectively].There were no statistically significant differences in clinical data between the two groups (all P>0.05). Univariate Logistic regression analysis showed that, among contrast-enhanced ultrasound features, the centripetal perfusion pattern, irregular perfusion defect type, and uneven distribution of contrast agent were significantly associated with cervical lymph node metastasis (all P<0.05). Among conventional ultrasound features, L/S ratio≤1.5, heterogeneous internal echoes, uneven cortex thickening, blurred corticomedullary boundary, loss of lymphatic gate structure, and peripheral or mixed type on color Doppler flow imaging were significantly associated with cervical lymph node metastasis (all P<0.05). Multivariate Logistic regression analysis indicated that the centripetal perfusion pattern, heterogeneous internal echoes, and uneven cortical thickening were independent risk factors for cervical lymph node metastasis (all P<0.05). A nomogram model was constructed based on the above independent risk factors, and offered an AUC of 0.933 (95%CI:0.890-0.976) in the training group, which was significantly higher than that for enhanced CT, enhanced MRI, conventional ultrasound, and conventional ultrasound combined with CEUS [AUC were 0.818 (95%CI:0.747-0.890), 0.807 (95%CI:0.739-0.875), 0.842 (95%CI: 0.777-0.908), and 0.921 (95%CI:0.876-0.967), respectively]. In the validation group, the AUC was 0.866 (95%CI:0.703-1.000), which was higher than that for cervical enhanced CT, enhanced MRI, and conventional ultrasound [AUC were 0.820 (95%CI:0.613-1.000), 0.711 (95%CI:0.478-0.943), and 0.748 (95%CI:0.515-0.982), respectively]. Conclusion: The combination of conventional ultrasound and CEUS has significant clinical application value in predicting cervical lymph node metastasis in HNSCC.

Cancer ENO2 Induces Histone Lactylation-Mediated M2 Macrophage Polarization and Facilitates Metastasis of Head and Neck Squamous Cell Carcinoma

Cancer ENO2 Induces Histone Lactylation-Mediated M2 Macrophage Polarization and Facilitates Metastasis of Head and Neck Squamous Cell Carcinoma

CT Multidimensional Radiomics Combined with Inflammatory Immune Score For Preoperative Prediction of Pathological Grade in Esophageal Squamous Cell Carcinoma.

CT Multidimensional Radiomics Combined with Inflammatory Immune Score For Preoperative Prediction of Pathological Grade in Esophageal Squamous Cell Carcinoma.

Transcriptome analysis and artificial intelligence for predicting lymph node metastasis of esophageal squamous cell carcinoma

Transcriptome analysis and artificial intelligence for predicting lymph node metastasis of esophageal squamous cell carcinoma

Metastatic Squamous Cell Carcinoma with Unknown Primary Origin in the Mediastinal Lymph Node

We report a case of a patient with squamous cell carcinoma metastasis confined to a mediastinal lymph node, with no identifiable primary tumor. The patient remains cancer-free 2 years after diagnosis. Although various theories exist regarding the etiology of lymph node carcinoma of unknown primary origin, advances in elucidating its pathogenesis and integrating treatment strategies based on genetic profiling are expected to form the foundation of future clinical practice.

Evaluation of Integrin Glycovariants as Biomarkers of Metastasis, Invasion, and Therapy Stratification in Head and Neck Squamous Cell Carcinoma.

Integrin glycosylation is one mechanism regulating the invasion and metastasis of malignant tumors. Little information exists about integrin glycosylation in head and neck squamous cell carcinoma (HNSCC). In this study, we evaluated the glycosylation of integrins in HNSCC tumor and serum samples. Intraoperative fresh tumor and normal tissue samples and blood samples were collected from HNSCC patients (N = 24). Lectin-bioaffinity assays using six nanoparticle-bound lectins were used to evaluate the glycosylation of integrins ITGA2, ITGA3, ITGA5, ITGA6, ITGB1, and ITGB4. Associations with metastasis, therapy response, and clinical factors were analyzed. Glycosylation profiles of the integrins were relatively similar. High intratumoral ITGB1-WFL results were associated with high T class, whereas none of the integrin glycovariant assays provided significant resolution in the detection of nodal metastasis. While the serum integrin glycovariant levels were low overall, serum ITGA2-UEA offered significant resolution in both radiotherapy response prediction and cancer recurrence prognostication. We demonstrate that while integrin glycovariants are abundant in HNSCC tumors and ITGB1-WFL was associated with invasiveness, integrin glycovariants do not directly correlate with metastatic behavior. Further, serum ITGA2-UEA appeared as a potential radioresponse biomarker.

Predictors of Inguinal Lymph Node Metastasis in Penile Squamous Cell Carcinoma: Insights from a Single-Center Retrospective Study.

Background: Squamous cell carcinoma (SCC) of the penis accounts for approximately 95% of penile cancers and is associated with substantial morbidity and mortality. SCC typically develops in uncircumcised men, most commonly affecting the foreskin or glans. While slow-growing, early detection is crucial to improve survival outcomes. Risk factors include advanced age, lack of circumcision, poor hygiene, HPV infection (types 16 and 18), chronic inflammation, and smoking. Methods: We conducted a retrospective, single-center study at IRCCS Hospital "G. Pascale" of Naples, Italy, involving 59 patients treated between January 2015 and January 2023. The inclusion criteria were surgically treated primary tumors, confirmed SCC pathology, and pathologically verified inguinal lymph node metastasis (ILNM). We analyzed clinical variables including lymph node involvement, lymphovascular invasion (LVI), spongiosum corpus involvement (SCI), HPV infection, and tumor differentiation. Univariate and multivariate logistic regression analyses were performed to determine independent predictors of ILNM. Results: The mean age of patients was 66.67 ± 13.97 years. ILNM was confirmed in 24 patients (40.6%), while 35 (59.3%) had no lymph node involvement. Univariate analysis identified lymph node involvement at diagnosis (p = 0.005), LVI (p = 0.003), and SCI (p = 0.003) as significant predictors of ILNM. These factors were confirmed in the multivariate analysis, with lymph node involvement (p = 0.004), LVI (p = 0.025), and SCI (p = 0.028) as independent predictors. Conclusions: Lymph node status, LVI, and SCI are significant predictors of ILNM in penile SCC. Identifying these factors can aid in risk stratification, optimizing surgical decisions, and potentially reducing unnecessary morbidity. Further large-scale studies are recommended to validate these findings and refine prognostic models.

Abstract 5235: Cancer associated fibroblasts-derived SULF1 facilitated carcinogenesis and metastasis of esophageal squamous cell carcinoma

Abstract Cancer-associated fibroblasts (CAFs) play a significant role in creating a supportive environment for tumor growth and progression. Esophageal squamous cell carcinoma (ESCC) ranks as the seventh leading cause of cancer-related deaths globally, characterized by poor clinical outcomes and limited treatment options. CAFs-based therapeutic strategies might benefit ESCC patients. In this study, we utilized single-cell RNA sequencing (scRNA-seq) data from four integrated ESCC cohorts to identify a unique protein, SULF1, secreted by CAFs. Primary human CAFs were isolated from six clinical samples of ESCC and various functional assays, such as transwell migration/invasion and co-culture/co-injection experiments, were conducted to assess the oncogenic or pro-metastatic effects of SULF1-secreting CAFs. Neutralizing antibodies against SULF1 was proposedly used for treatment. Here, we revealed that CAFs exhibited the highest expression levels of SULF1 compared to other cell types based on scRNA-seq data. Immunohistochemistry and immunofluorescence staining confirmed the unique expression of SULF1 in CAFs, particularly in αSMA-rich CAFs within ESCC patient samples. Furthermore, extracellular secretion of SULF1 was elevated in primary human CAFs compared to tumor cells and normal fibroblasts. Co-culture or co-injection of SULF1-knockdown CAFs mixed with tumor cells significantly inhibited tumor growth and metastasis both in vivo and in vitro. Mechanistically, RNA-seq data suggested that CAF-derived SULF1 might activate the TGF-beta and PI3K-AKT signaling pathways, thereby mediating the aggressive behavior of tumor cells. Notably, blocking SULF1-secreted CAFs resulted in suppression of ESCC tumor growth and progression in vivo. Collectively, CAF-secreted SULF1 emerged as a critical mediator in educating the ESCC tumor microenvironment and promoting tumor aggressiveness. Targeting SULF1-expressing CAFs could be viewed as a potential therapeutic strategy for ESCC treatment. Citation Format: Hongyu Zhou, Beilei Liu, Licheng Tan, Baifeng Zhang, Yingchen lyu, Xin-Yuan Guan. Cancer associated fibroblasts-derived SULF1 facilitated carcinogenesis and metastasis of esophageal squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5235.

Diagnostic Value of Dual-Energy CT Iodine Mapping in Differentiating Malignant and Benign Cervical Lymphadenopathies.

To evaluate the diagnostic accuracy of Dual-Energy Computed Tomography (DECT) in distinguishing malignant from benign cervical lymph nodes in neck carcinoma based on iodine concentration and normalized spectral attenuation (Hounsfield Unit, HU) values. Retrospective DECT scan analysis was performed on 52 neck carcinoma patients, analyzing 52 metastatic and 28 reactive lymph nodes. Iodine concentration (mg/mL) and spectral HU values were measured with circular regions of interest on iodine maps. Metastatic nodes included 27 from squamous cell carcinoma (SCC), 19 from lymphoma, and 6 from papillary thyroid carcinoma (PTC). Metastatic lymph nodes had lower iodine levels than reactive nodes (1.45 vs. 1.85 mg/mL, p = 0.011). No significant difference in spectral HU values was found (117 vs. 111 HU, p = 0.328). An iodine threshold of 1.62 mg/mL demonstrated 71% sensitivity and 77% specificity for detecting malignancy (AUC = 0.673, 95% CI: 0.54-0.80, p = 0.011). SCC metastases had lower iodine levels than reactive nodes (1.33 vs. 1.85 mg/mL, p < 0.001), while PTC metastases had higher levels (2.39 vs. 1.85 mg/mL, p = 0.038). DECT iodine quantification improves the detection of cervical lymph node metastases, particularly in cases with equivocal size criteria. Incorporating iodine measurements with tumor type knowledge improves diagnostic accuracy, aiding in prognosis and treatment planning.

SRPK1 Activation Facilitates Gli3S664 Phosphorylation and Promotes Metastasis in Esophageal Squamous Cell Carcinoma.

Esophageal squamous cell carcinoma (ESCC) stands out as one of the most malignant digestive tumors, with its prognosis marred by frequent metastasis and recurrence. However, the mechanism behind ESCC metastasis remains elusive, impeding therapeutic advancements. SRPK1 emerges as an independent prognostic marker for ESCC patients. Our research illuminates the consequential role of SRPK1, where its genetic knockout led to decreased levels of transcription factors Snail and Slug, concomitant with an enhanced expression of the cell-to-cell adhesion protein E-cadherin. Conversely, reintroducing an overexpression of SRPK1 reversed the effects, highlighting its essential role in ESCC metastasis. Through bioinformatics analysis, we identified a correlation between SRPK1 and Gli3. Furthermore, increased levels of Gli3 and its phosphorylated form, p-Gli3S664, were detected in ESCC tissues, which are implicated in promoting ESCC metastasis. Notably, our research confirmed that SRPK1 promotes migration, invasion, and epithelial-mesenchymal transition (EMT) of ESCC cells through phosphorylates Gli3 at ser 664. Additional investigations reveal that dihydroartemisinin (DHA) effectively impedes ESCC cell metastasis by suppressing SRPK1-mediated phosphorylation of Gli3S664 both in vitro and in vivo. Consequently, our study underscores the pivotal role of the SRPK1-p-Gli3S664 axis in ESCC metastasis and suggests DHA as a promising candidate for preventing ESCC metastasis by targeting this axis.

Bilateral Neck Dissection in cN0 Supraglottic Squamous Cell Carcinoma: Essential or Not?

There is controversy regarding bilateral neck dissection for cN0 supraglottic squamous cell carcinoma. This study aimed to explore the risk factor of occult isolated contralateral/bilateral metastasis in cN0 supraglottic squamous cell carcinoma and help clinicians better make assessments for these patients. PubMed, the Cochrane Library, CNKI, and CBM were systematically searched for studies on occult lymph node metastasis in cN0 supraglottic squamous cell carcinoma from the inception of each database to May 30, 2024. All patients with supraglottic squamous cell carcinoma and a clinical N0 neck, who had complete records of neck lymph node metastasis, were included in the study. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guideline was followed to extract data. Data were pooled using a random-effects generalized linear mixed model with 95% confidence intervals (CIs). The risk of occult isolated contralateral/bilateral metastatic lymph nodes was analyzed. Fifteen studies including 1609 patients with cN0 supraglottic squamous cell carcinoma were analyzed. The pooled risk of occult isolated contralateral/bilateral metastasis was 7.49% (95% CI: 5.65%-9.87%; I2 = 57%). For Type A tumors, the risk was 4.14% (95% CI: 2%-64%; I2 = 81%), 6.74% for Type B (95% CI: 2.27%-18.33%, I2 = 82%), and 13.62% for Type C (95% CI: 5.82%-28.66%, I2 = 69%). For T1-T2 patients, the risk was 5.18% (95% CI: 2%-64%; I2 = 81%), and 8.73% (95% CI: 5.92%-12.69%, I2 = 0%)for T3-T4 patients. When ipsilateral pN+ was present, the risk increased to 20.97% (95% CI: 16.09%-26.85%, I2 = 29%). Contralateral neck dissection is recommended for Type C patients. Pathologically ipsilateral metastasis confirmed patients should receive contralateral neck dissection, radiotherapy, or even active surveillance follow-up.

Deep learning-based prediction of enhanced CT scans for lymph node metastasis in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) poses a significant global health challenge with a particularly grim prognosis. Accurate prediction of lymph node metastasis (LNM) in ESCC is crucial for optimizing treatment strategies and improving patient outcomes. This study leverages the power of deep learning, specifically Convolutional Neural Networks (CNN) and Long Short-Term Memory (LSTM) networks, to analyze arterial phase enhanced CT images and predict LNM in ESCC patients. A retrospective study included 441 ESCC patients who underwent radical esophagectomy and regional lymphadenectomy. CT imaging was performed using contrast-enhanced CT scanners. Tumor region segmentation was conducted to determine the region of interest (ROI), where local tumor 3D volumes were extracted as input for the model. The novel deep learning model, LymphoReso-Net, combined CNN and LSTM networks to process and learn from medical imaging data. The model outputs a binary prediction for LNM. GRAD-CAM was integrated to enhance model interpretability. Performance was evaluated using fivefold cross-validation with metrics including accuracy, sensitivity, specificity, and AUC-ROC. The gold standard for LNM confirmation was pathologically confirmed LNM shortly after the CT. LymphoReso-Net demonstrated promising performance with an average accuracy of 0.789, an AUC of 0.836, a sensitivity of 0.784, and a specificity of 0.797. GRAD-CAM provided visual explanations of the model's decision-making, aiding in identifying critical regions associated with LNM prediction. This study introduces a novel deep learning framework, LymphoReso-Net, for predicting LNM in ESCC patients. The model's accuracy and interpretability offer valuable insights into lymphatic spread patterns, enabling more informed therapeutic decisions.

FAO-fueled OXPHOS and NRF2-mediated stress resilience in MICs drive lymph node metastasis

Metastasis is an inefficient process requiring cancer cells to adapt metabolically for survival and colonization in new environments. The contributions of tumor metabolic reprogramming to lymph node (LN) metastasis and its underlying mechanisms remain elusive. Through single-cell RNA sequencing, we identified rare metastasis-initiating cells (MICs) with stem-like properties that drive early LN metastasis. Integrated transcriptome, lipidomic, metabolomic, and functional analyses demonstrated that MICs depend on oxidative phosphorylation (OXPHOS) fueled by fatty acid oxidation (FAO) in the lipid-rich LN microenvironment. Mechanistically, the NRF2-SLC7A11 axis promotes glutathione synthesis to mitigate oxidative stress, thereby enhancing stress resistance and metastatic potential of MICs. Inhibition of NRF2-SLC7A11 reduced LN metastasis and sensitized tumors to cisplatin. Clinically, elevated NRF2-SLC7A11 expression was observed in tumors, with high expression correlating with LN metastasis, chemoresistance, and poor prognosis in esophageal squamous cell carcinoma (ESCC). These findings highlight the pivotal roles of FAO-fueled OXPHOS and NRF2 in LN metastasis and suggest targeting these pathways as a promising therapeutic strategy for metastatic ESCC.

AKAP12, mediated by transcription factor 21, inhibits cell proliferation, metastasis, and glycolysis in lung squamous cell carcinoma.

A-kinase anchor protein 12 (AKAP12) has been reported to be related to lung squamous cell carcinoma (LUSC) progression. However, its role and molecular mechanisms in LUSC have not been revealed. The mRNA and protein levels of AKAP12 and transcription factor 21 (TCF21) were tested by quantitative real-time PCR and western blot. Cell counting kit 8 assay, EdU assay, flow cytometry, wound healing assay, and transwell assay were used to evaluate cell proliferation, apoptosis, migration, and invasion. Cell glycolysis was measured by testing glucose consumption and lactate production. The interaction between AKAP12 and TCF21 was assessed by ChIP assay and dual-luciferase reporter assay. A mice xenograft model was constructed to explore AKAP12 and TCF21 roles in vivo. Our data showed that AKAP12 was underexpressed in LUSC tissues and cells, and its overexpression inhibited LUSC cell growth, metastasis, and glycolysis. TCF21 had decreased expression in LUSC, which facilitated AKAP12 expression through binding to its promoter region to enhance its transcription. Furthermore, TCF21 increased AKAP12 expression to repress LUSC cell growth, metastasis, and glycolysis. In vivo experiments showed that AKAP12 upregulation reduced LUSC tumorigenesis, and TCF21 knockdown reversed this effect. In conclusion, AKAP12 might be a tumor suppressor in LUSC, which was mediated by TCF21 and could inhibit cell growth, metastasis, and glycolysis to restrain LUSC malignant progression.

Correlation of Histological Grading with Regional Metastasis in Oral Squamous Cell Carcinoma – A Cross-Sectional Study

ABSTRACT Histological grading is a crucial diagnostic technique for forecasting the molecular and clinical characteristics of cancer. A bad prognosis for mouth cancer is indicated by cervical lymph node metastases. There is a correlation between lymph node metastases and TNM staging, Broder’s grading system, and Anneroth grading system. The purpose of this study is to examine how histological malignancy is graded in connection to metastases in the cervical lymph nodes using Broder’s classification and the Anneroth grading system of biopsy specimens. Materials and Procedures: The study comprised 50 participants with oral squamous cell carcinoma (OSCC). Fifteen metastatic cases and 35 nonmetastatic tumor specimens were compared. Every patient was graded using the Anneroth grading method, Broder’s system, and TNM. There was no discernible difference between metastasis and Broder’s grading system. There was a statistically significant difference between metastasis and the Anneroth grading system. In conclusion, Anneroth’s categorization of OSCC’s multifactorial grading system may be a useful diagnostic and prognostic indicator for lymph node metastases.

HPV‐Positive Squamous Cell Carcinoma Metastasis Without Clinical Evidence of Primary: The Posterior Oropharyngeal Wall May Be an Overlooked Location

ABSTRACTBackgroundOropharyngeal squamous cell carcinoma (SCC) can present as cancer of unknown primary, where only cervical lymph node metastases are identified. Most tumors, particularly human‐papillomavirus‐associated ones, are located in the palatine/lingual tonsils. When this is not the case, additional imaging with 2‐deoxy‐2‐[18F]fluoro‐D‐glucose positron emission tomography ([18F]FDG‐PET) and ultrasound can be helpful.MethodsA 68‐year‐old male with bilateral cervical metastasis from an HPV‐positive SCC, no primary tumor was identified despite thorough examination. [18F]FDG‐PET revealed bilateral cervical metastases and a possible primary tumor in the posterior oropharynx. Guided by perioperative transoral ultrasound, a biopsy for frozen sectioning was obtained.ResultsFrozen sectioning of the posterior tumor revealed SCC. Final histology confirmed the posterior wall tumor as the primary cancer.ConclusionsThe posterior oropharynx wall must be carefully investigated during the diagnostic workup for SCC of an unknown primary tumor as it can be the site of the primary tumor. Identification of the primary tumor reduces the need for further diagnostic surgery.