Metastasis Of Squamous Cell Carcinoma Research Articles

Histone 3 lysine 9 acetylation-specific reprogramming regulates esophageal squamous cell carcinoma progression and metastasis.

Dysregulation of histone acetylation is widely implicated in tumorigenesis, yet its specific roles in the progression and metastasis of esophageal squamous cell carcinoma (ESCC) remain unclear. Here, we profiled the genome-wide landscapes of H3K9ac for paired adjacent normal (Nor), primary ESCC (EC) and metastatic lymph node (LNC) esophageal tissues from three ESCC patients. Compared to H3K27ac, we identified a distinct epigenetic reprogramming specific to H3K9ac in EC and LNC samples relative to Nor samples. This H3K9ac-related reprogramming contributed to the transcriptomic aberration of targeting genes, which were functionally associated with tumorigenesis and metastasis. Notably, genes with gained H3K9ac signals in both primary and metastatic lymph node samples (common-gained gene) were significantly enriched in oncogenes. Single-cell RNA-seq analysis further revealed that the corresponding top 15 common-gained genes preferred to be enriched in mesenchymal cells with high metastatic potential. Additionally, in vitro experiment demonstrated that the removal of H3K9ac from the common-gained gene MSI1 significantly downregulated its transcription, resulting in deficiencies in ESCC cell proliferation and migration. Together, our findings revealed the distinct characteristics of H3K9ac in esophageal squamous cell carcinogenesis and metastasis, and highlighted the potential therapeutic avenue for intervening ESCC through epigenetic modulation via H3K9ac.

Multi-omics analysis reveals NNMT as a master metabolic regulator of metastasis in esophageal squamous cell carcinoma

Metabolic reprogramming has been observed in cancer metastasis, whereas metabolic changes required for malignant cells during lymph node metastasis of esophageal squamous cell carcinoma (ESCC) are still poorly understood. Here, we performed single-cell RNA sequencing (scRNA-seq) of paired ESCC tumor tissues and lymph nodes to uncover the reprogramming of tumor microenvironment (TME) and metabolic pathways. By integrating analyses of scRNA-seq data with metabolomics of ESCC tumor tissues and plasma samples, we found nicotinate and nicotinamide metabolism pathway was dysregulated in ESCC patients with lymph node metastasis (LN+), exhibiting as significantly increased 1-methylnicotinamide (MNA) in both tumors and plasma. Further data indicated high expression of N-methyltransferase (NNMT), which converts active methyl groups from the universal methyl donor, S-adenosylmethionine (SAM), to stable MNA, contributed to the increased MNA in LN+ ESCC. NNMT promotes epithelial–mesenchymal transition (EMT) and metastasis of ESCC in vitro and in vivo by inhibiting E-cadherin expression. Mechanically, high NNMT expression consumed too much active methyl group and decreased H3K4me3 modification at E-cadherin promoter and inhibited m6A modification of E-cadherin mRNA, therefore inhibiting E-cadherin expression at both transcriptional and post-transcriptional level. Finally, a detection method of lymph node metastasis was build based on the dysregulated metabolites, which showed good performance among ESCC patients. For lymph node metastasis of ESCC, this work supports NNMT is a master regulator of the cross-talk between cellular metabolism and epigenetic modifications, which may be a therapeutic target.

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.

Cyclic increase in the ADAMTS1-L1CAM-EGFR axis promotes the EMT and cervical lymph node metastasis of oral squamous cell carcinoma

The matrix metalloprotease A disintegrin and metalloprotease with thrombospondin motifs 1 (ADAMTS1) was reported to be involved in tumor progression in several cancer types, but its contributions appear discrepant. At present, the role of ADAMTS1 in oral squamous cell carcinoma (SCC; OSCC) remains unclear. Herein, The Cancer Genome Atlas (TCGA) database showed that ADAMTS1 transcripts were downregulated in head and neck SCC (HNSCC) tissues compared to normal tissues, but ADAMTS1 levels were correlated with poorer prognoses of HNSCC patients. In vitro, we observed that ADAMTS1 expression levels were correlated with the invasive abilities of four OSCC cell lines, HSC-3, SCC9, HSC-3M, and SAS. Knockdown of ADAMTS1 in OSCC cells led to a decrease and its overexpression led to an increase in cell-invasive abilities in vitro as well as tumor growth and lymph node (LN) metastasis in OSCC xenografts. Mechanistic investigations showed that the cyclic increase in ADAMTS1-L1 cell adhesion molecule (L1CAM) axis-mediated epidermal growth factor receptor (EGFR) activation led to exacerbation of the invasive abilities of OSCC cells via inducing epithelial-mesenchymal transition (EMT) progression. Clinical analyses revealed that ADAMTS1, L1CAM, and EGFR levels were all correlated with worse prognoses of HNSCC patients, and patients with ADAMTS1high/L1CAMhigh or EGFRhigh tumors had the shortest overall and disease-specific survival times. As to therapeutic aspects, we discovered that an edible plant-derived flavonoid, apigenin (API), drastically inhibited expression of the ADAMTS1-L1CAM-EGFR axis and reduced the ADAMTS1-triggered invasion and LN metastasis of OSCC cells in vitro and in vivo. Most importantly, API treatment significantly prolonged survival rates of xenograft mice with OSCC. In summary, ADAMTS1 may be a useful biomarker for predicting OSCC progression, and API potentially retarded OSCC progression by targeting the ADAMTS1-L1CAM-EGFR signaling pathway.

Metastasis of skin squamous cell carcinoma in kidney transplant recipients.

Cutaneous squamous cell carcinoma (cSCC) is the most common skin malignancy in kidney transplant recipients (KTRs) as a result of immunosuppression. A worldwide increase in kidney transplantation justifies the determination of prognostic biomarkers by collecting detailed patient data on metastasis development. This study aims to characterize the clinical, epidemiological, and histopathological profiles of KTRs who developed metastasis of cSCC. We conducted a retrospective single-center study on 18 KTRs and 21 immunocompetent patients (ICs) with metastatic cSCC, using data from 2004 to 2021. ICs were older (median age 70.5 years) than KTRs (median age: 59.5 years). Both groups were predominantly male with Fitzpatrick skin phototype I/II. The primary tumor appeared around 83.5 months post-transplant, usually in sun-exposed areas (61.1%), though some non-exposed areas in ICs (23.8%) contradicted literature findings. KTRs took longer to develop metastasis (median: 11.0 months) compared to ICs (median: 5.5 months). The mean size of the primary tumor was smaller in KTRs (2.50 cm2) compared to ICs (4.55 cm2). The main lymph node chain affected by metastasis wasparotid lymph nodes in KTRs (27.8%) and cervical/axillar lymph nodes in ICs (both 19.0%). Both groups exhibited similar primary tumor grades and metastasis evolution, but KTRs had a higher prevalence of lymphovascular invasion. Metastasis of cSCC was more common in males with low skin phototype, in KTRs, particularly on the head and neck. The study suggests a possible link between lymphovascular invasion and metastasis development in KTRs.

Serine/Threonine Kinase (STK) 33 promotes the proliferation and metastasis of human esophageal squamous cell carcinoma via inflammation-related pathway

The serine/threonine kinase (STK) 33 plays a key role in cancer cell proliferation and metastasis. Abnormal STK33 expression is closely related to malignancy of numerous cancers. This study suggests the important role of STK33 in the pathogenesis and metastatic progression of esophageal squamous cell carcinoma (ESCC). STK33 expression in human ESCC tissues was detected by immunohistochemical technique. Further, we analyzed the relationship between STK33 and clinical and pathological factors as well as the prognosis of patients. ECa109 cell line was cultured and transfected with STK33-RNAi lentiviral vector to perform Hochest33342 & PI and metastasis experiments. The TCGA database was used to analyze the STK33 expression level in ESCC. All statistical analyses were performed in SPSS 23.0 software. Differences with P < 0.05 were considered statistically significant. In human ESCC specimens, STK33 was overexpressed and associated with poor prognosis. Silencing STK33 expression suppressed ESCC proliferation, migration, invasion, and tumor growth. STK33 also mediated angiogenesis, TGFβ, and inflammatory response in ESCC. Mechanistic investigations revealed that STK33 regulates ESCC through multiple complex pathways. Dysregulated STK33 signaling promotes ESCC growth and progression. Thus, our findings identified STK33 as a candidate treatment target that improves ESCC therapy.

Circ_FNDC3B Promotes Cell Proliferation and Metastasis in Esophageal Squamous Cell Carcinoma via Regulating MAPK1 by Binding to miR-136-5p.

A handful of circular RNAs (circRNAs) associated with cancer progression have been indicated in esophageal squamous cell carcinoma (ESCC). The current study aimed to investigate the functional mechanism of circular RNA Fibronectin type III domain containing 3B (circ_FNDC3B) in ESCC. Circ_FNDC3B, FNDC3B, microRNA-136-5p (miR-136-5p) and mitogen-activated protein kinase 1 (MAPK1) were examined via the quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation was evaluated by Cell Counting Kit-8 (CCK-8) and colony formation assays. Transwell assay was performed to measure cell migration and invasion. Protein analysis was implemented by western blot. Cell apoptosis was assessed via flow cytometry. Target interaction was affirmed using dual-luciferase reporter assay. The function analysis of circ_FNDC3B in vivo was explored by xenograft models. The upregulation of circ_FNDC3B was detected in ESCC tissues and cells. Functionally, ESCC cell proliferation and metastasis were repressed but apoptosis was promoted by circ_FNDC3B knockdown. Besides, circ_FNDC3B silence inhibited ESCC progression through MAPK1 downregulation. Further target analysis identified miR-136-5p as a target of circ_FNDC3B and an upstream control of MAPK1. Additionally, the regulation of si-circ_FNDC3B in ESCC was also dependent on targeting miR-136-5p. Moreover, circ_FNDC3B targeted miR-136-5p to affect MAPK1 level. Tumorigenesis in vivo was also suppressed by downregulating circ_FNDC3B to regulate miR-136-5p/MAPK1 axis. Circ_FNDC3B downregulation impeded the development of ESCC via the mediation of miR-136-5p/MAPK1 axis. This report afforded a novel insight into the functional mechanism of circ_FNDC3B in ESCC.

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.

Identification and Validation of a Prognostic Signature Derived from the Cancer Stem Cells for Oral Squamous Cell Carcinoma.

The progression and metastasis of oral squamous cell carcinoma (OSCC) are highly influenced by cancer stem cells (CSCs) due to their unique self-renewal and plasticity. In this study, data were obtained from a single-cell RNA-sequencing dataset (GSE172577) in the GEO database, and LASSO-Cox regression analysis was performed on 1344 CSCs-related genes to establish a six-gene prognostic signature (6-GPS) consisting of ADM, POLR1D, PTGR1, RPL35A, PGK1, and P4HA1. High-risk scores were significantly associated with unfavorable survival outcomes, and these features were thoroughly validated in the ICGC. The results of nomograms, calibration plots, and ROC curves confirmed the good prognostic accuracy of 6-GPS for OSCC. Additionally, the knockdown of ADM or POLR1D genes may significantly inhibit the proliferation, migration, and invasion of OSCC cells through the JAK/HIF-1 pathway. Furthermore, cell-cycle arrest occurred in the G1 phase by suppressing Cyclin D1. In summary, 6-GPS may play a crucial role in the occurrence and development of OSCC and has the potential to be developed further as a diagnostic, therapeutic, and prognostic tool for OSCC.

Exacerbated prognostic impact of multiple intramural metastasis versus single intramural metastasis of thoracic esophageal squamous cell carcinoma: evidence from an Uzbekistan cohort.

Intramural metastasis (IM) is a poor prognostic factor for patients with esophageal squamous cell carcinoma (ESCC). We conducted this study to assess the prognostic impact of IM in an Uzbekistan cohort and to identify the factors associated with the poor prognosis of patients with ESCC and IM. The subjects of this retrospective analysis were 1083 patients with thoracic ESCC, who underwent curative esophagectomy between 2001 and 2021 at the National Cancer Center of Uzbekistan. We compared the clinicopathological characteristics and survival outcomes of patients with versus those without IM and evaluated the factors associated with the poor prognosis of patients with IM. Patients with pathological IM (n = 59, 5.4%) were significantly older, had a higher percentage of lymphatic invasion and worse pathological N stage, and had shorter overall survival (OS) than patients without IM. Multivariable analysis of OS identified multiple IMs as the only independent prognostic factor in patients with IM (hazard ratio, 6.04; 95% confidence interval, 2.77-13.18; P < 0.001). Patients with multiple IMs had shorter OS and recurrence-free survival than those with a single IM. IM was a poor prognostic factor for patients with ESCC in this Uzbekistan cohort and multiple IMs were associated with worse outcomes.

Development and validation of a nomogram to predict cervical lymph node metastasis in head and neck squamous cell carcinoma.

Head and neck cancers are a heterogeneous, aggressive, and genetically complex collection of malignancies of the oral cavity, nasopharynx, oropharynx, hypopharynx, larynx, paranasal sinuses and salivary glands, which are difficult to treat. Regional lymph nodes metastasis is a significant poor prognosis factor for head and neck squamous cell carcinoma. Metastasis to the regional lymph nodes reduces the 5-year survival rate by 50% compared with that of patients with early-stage disease. Accurate evaluation of cervical lymph node is a vital component in the overall treatment plan for patients with squamous cell carcinoma of the head and neck. However, current models are struggle to accurately to predict cervical lymph node metastasis. Here, we analyzed the clinical, imaging, and pathological data of 272 patients with HNSCC confirmed by postoperative pathology and sought to develop and validate a nomogram for prediction of lymph node metastasis in patients with head and neck squamous cell carcinoma. We retrospectively analyzed the clinical, imaging, and pathological data of 272 patients with head and neck squamous cell carcinoma (HNSCC) confirmed by postoperative pathology at the Affiliated Hospital of Qingdao University from June 2017 to June 2021. Patients were randomly divided into the training and validation cohorts in a 3:1 ratio, and after screening risk factors by logistic regression, nomogram was developed for predicting lymph nodes metastasis, then the prediction model was verified by C-index, area under curve (AUC), and calibration curve. Of the 272 patients, seven variables were screened to establish the predictive model, including the differentiation degree of the tumor [95% confidence interval(CI):1.224~6.735, P=0.015], long-to-short axis ratio of the lymph nodes (95%CI: 0.019~0.217, P<0.001), uneven/circular enhancement (95%CI: 1.476~16.715, P=0.010), aggregation of lymph nodes (95%CI:1.373~10.849, P=0.010), inhomogeneous echo (95%CI: 1.337~23.389, P=0.018), unclear/absent medulla of lymph nodes (95%CI: 2.514~43.989, P=0.001), and rich blood flow (95%CI: 1.952~85.632, P=0.008). The C-index was 0.910, areas under the curve of training cohort and verification cohort were 0.953 and 0.938 respectively, indicating the discriminative ability of this nomogram. The calibration curve showed a favorable compliance between the prediction of the model and actual observations. The clinical decision curve showed this model is clinically useful and had better discriminative ability between 0.25 and 0.9 for the probability of cervical LNs metastasis. We established a good prediction model for cervical lymph node metastasis in head and neck squamous cell carcinoma patients which can provide reference value and auxiliary diagnosis for clinicians in making neck management decisions of HNSCC patients.

Comparing three-dimensional and two-dimensional deep-learning, radiomics, and fusion models for predicting occult lymph node metastasis in laryngeal squamous cell carcinoma based on CT imaging: a multicentre, retrospective, diagnostic study

The occult lymph node metastasis (LNM) of laryngeal squamous cell carcinoma (LSCC) affects the treatment and prognosis of patients. This study aimed to comprehensively compare the performance of the three-dimensional and two-dimensional deep learning models, radiomics model, and the fusion models for predicting occult LNM in LSCC. In this retrospective diagnostic study, a total of 553 patients with clinical N0 stage LSCC, who underwent surgical treatment without distant metastasis and multiple primary cancers, were consecutively enrolled from four Chinese medical centres between January 01, 2016 and December 30, 2020. The participant data were manually retrieved from medical records, imaging databases, and pathology reports. The study cohort was divided into a training set (n=300), an internal test set (n=89), and two external test sets (n=120 and 44, respectively). The three-dimensional deep learning (3D DL), two-dimensional deep learning (2D DL), and radiomics model were developed using CT images of the primary tumor. The clinical model was constructed based on clinical and radiological features. Two fusion strategies were utilized to develop the fusion model: the feature-based DLRad_FB model and the decision-based DLRad_DB model. The discriminative ability and correlation of 3D DL, 2D DL and radiomics features were analysed comprehensively. The performances of the predictive models were evaluated based on the pathological diagnosis. The 3D DL features had superior discriminative ability and lower internal redundancy compared to 2D DL and radiomics features. The DLRad_DB model achieved the highest AUC (0.89-0.90) among all the study sets, significantly outperforming the clinical model (AUC=0.73-0.78, P=0.0001-0.042, Delong test). Compared to the DLRad_DB model, the AUC values for the DLRad_FB, 3D DL, 2D DL, and radiomics models were 0.82-0.84 (P=0.025-0.46), 0.86-0.89 (P=0.75-0.97), 0.83-0.86 (P=0.029-0.66), and 0.79-0.82 (P=0.0072-0.10), respectively in the study sets. Additionally, the DLRad_DB model exhibited the best sensitivity (82-88%) and specificity (79-85%) in the test sets. The decision-based fusion model DLRad_DB, which combines 3D DL, 2D DL, radiomics, and clinical data, can be utilized to predict occult LNM in LSCC. This has the potential to minimize unnecessary lymph node dissection and prophylactic radiotherapy in patients with cN0 disease. National Natural Science Foundation of China, Natural Science Foundation of Shandong Province.

A-313 - Desmoplasia, a risk factor for recurrence and metastasis in cutaneous squamous cell carcinoma: an interobserver agreement study among dermatopathologists

A-313 - Desmoplasia, a risk factor for recurrence and metastasis in cutaneous squamous cell carcinoma: an interobserver agreement study among dermatopathologists

Cucurbitacin B Inhibits the Malignancy of Esophageal Carcinoma through the KIF20A/JAK/STAT3 Signaling Pathway.

This study intends to explore the effects of Cucurbitacin B (CuB) and KIF20A on esophageal carcinoma (ESCA). Data were downloaded from the Cancer Genome Atlas (TCGA) database. The expression properties of KIF20A have been confirmed by GEPIA and ualcan from TCGA. The expression of KIF20A was determined using western blotting in ECA109 and KYSE150 cells after transfection with KIF20A, KIF20A siRNA, or numerical control siRNA (si-NC). Then, different concentrations of CuB were used to treat ECA109 and KYSE150 cells. CCK-8 and colony formation assays were used to measure cell viability, and a Transwell assay was utilized to assess cell migration and invasion ability. N-cadherin, E-cadherin, snail, p-Janus kinase 2 (JAK2), JAK2, p-signal transducer and activator of transcription 3 (STAT3), and STAT3 expression levels were evaluated using western blot. KIF20A was higher expressed in ESCA than in normal cells, and its overexpression was associated with squamous cell carcinoma, TNM stage, and lymph nodal metastasis of ESCA patients. In ECA109 and KYSE150 cells, increased KIF20A facilitated cell proliferation, migration, and invasion, whereas the knockdown of KIF20A can reverse these effects with N-cadherin. Snail expression diminished and E-cadherin increased. Similarly, CuB treatment could inhibit cell proliferation, migration, and invasion concentration dependently. Furthermore, KIF20A accelerated the expression of p-JAK2 and p-STAT3, while the application of CuB inhibited KIF20A expression and attenuated the activation of the JAK/STAT3 pathway. These findings revealed that CuB could inhibit the growth, migration, and invasion of ESCA through downregulating the KIF20A/JAK/STAT3 signaling pathway, and CuB could serve as an essential medicine for therapeutic intervention.

Let-7b miRNA-loaded nanostructures inhibited human tongue squamous cell carcinoma metastasis by the MOR-SRC-EGFR axis

miRNA is a type of classic non-coding RNA which is enriched in cancer. Various studies reported that miRNA be involved in the progression and metastasis of TSCC. Exploring pivotal miRNAs and elaborating the mechanisms inducing metastasis are important for improving the prognosis of TSCC patients. Here, Let-7b miRNA was identified as a significant factor contributing to metastasis of TSCC via directly targeting the 3′UTR of MOR mRNA, which leads to abnormally high expression of MOR protein. MORmightbindwithSRCandpotentiallyactivatep-EGFRthroughSRC. As a treatment modality, Let-7b miRNA mimics were encapsulated into the endosomal pH-responsive nanoparticles. NPs (Let-7b miRNA mimics) significantly inhibited Cal27 cells in vitro and in vivo metastatic model. Altogether, our data revealed that Let-7b miRNA-MOR-SRC-EGFR axis might be an effective therapeutic target in TSCC metastasis.

A deep learning and radiomics fusion model based on contrast-enhanced computer tomography improves preoperative identification of cervical lymph node metastasis of oral squamous cell carcinoma.

In this study, we constructed and validated models based on deep learning and radiomics to facilitate preoperative diagnosis of cervical lymph node metastasis (LNM) using contrast-enhanced computed tomography (CECT). CECT scans of 100 patients with OSCC (217 metastatic and 1973 non-metastatic cervical lymph nodes: development set, 76 patients; internally independent test set, 24 patients) who received treatment at the Peking University School and Hospital of Stomatology between 2012 and 2016 were retrospectively collected. Clinical diagnoses and pathological findings were used to establish the gold standard for metastatic cervical LNs. A reader study with two clinicians was also performed to evaluate the lymph node status in the test set. The performance of the proposed models and the clinicians was evaluated and compared by measuring using the area under the receiver operating characteristic curve (AUC), accuracy (ACC), sensitivity (SEN), and specificity (SPE). A fusion model combining deep learning with radiomics showed the best performance (ACC, 89.2%; SEN, 92.0%; SPE, 88.9%; and AUC, 0.950 [95% confidence interval: 0.908-0.993, P < 0.001]) in the test set. In comparison with the clinicians, the fusion model showed higher sensitivity (92.0 vs. 72.0% and 60.0%) but lower specificity (88.9 vs. 97.5% and 98.8%). A fusion model combining radiomics and deep learning approaches outperformed other single-technique models and showed great potential to accurately predict cervical LNM in patients with OSCC. The fusion model can complement the preoperative identification of LNM of OSCC performed by the clinicians.

The Correlation Between Depth of Invasion, and Degree of Differentiation with Cervical Lymph Node Metastasis in Oral Squamous Cell Carcinoma

Objective: To study the significance of Depth of invasion (DOI), and the degree of differentiation (DOD) as predictors of cervical nodalmetastasis in oral squamous cell carcinoma. To determine a cut-off depth beyond which there is a high risk of cervical metastasis. Todetermine whether the DOI can be is alone enough as predictor for lymphatic metastasis despite the DOD. Methods: Forty-eight patients with OSCC were included in the study 28 males and 20 females ranging between 25 to 80 years. Alltreated in Ghazi Al-Hariri hospital for surgical specialties in Baghdad Medical city between 2017 to 2019. Slides were examined afterimmunohistochemical staining. Depth of invasion was measured according to the criteria of AJCC, and the WHO system of grading was, all histopathological parameters were recorded after immunohistochemical staining. Results: The depth of invasion ranged between 2 and 13 mm with a mean of 6.58 mm and SD of ± 2.56 mm and it was found to be ahighly significant predictor for lymphatic metastasis (P-value = 0.001), the cut-off point with a significant risk of metastasis was 5 mm. Thedegree of differentiation was also a significant predictor for cervical metastasis (P-value = 0.024) with poorly differentiated SCC carrying the highest risk of cervical metastasis despite the depth of the tumor invasion. Conclusion: DOI and DOD were significant histological parameters that predict the behavior of the well and moderately differentiated oral squamous cell carcinoma and hence the management of the neck in OSCC. However, the depth of invasion was not significance in cases of poorly differentiated OSCC. Therefore, we recommend that elective neck dissection should be done in cases of poorly differentiated OSCC despite the DOI.

Risk factors and a predictive nomogram for lymph node metastasis in superficial esophageal squamous cell carcinoma.

Superficial esophageal squamous cell carcinoma (ESCC) is defined as cancer infiltrating the mucosa and submucosa, regardless of regional lymph node metastasis (LNM). Endoscopic resection of superficial ESCC is suitable for lesions that have no or low risk of LNM. Patients with a high risk of LNM always need further treatment after endoscopic resection. Therefore, accurately assessing the risk of LNM is critical for additional treatment options. To analyze risk factors for LNM and develop a nomogram to predict LNM risk in superficial ESCC patients. Clinical and pathological data of superficial ESCC patients undergoing esophagectomy from January 1, 2009 to January 31, 2016 were collected. Logistic regression analysis was used to predict LNM risk factors, and a nomogram was developed based on risk factors derived from multivariate logistic regression analysis. The receiver operating characteristic (ROC) curve was used to obtain the accuracy of the nomogram model. A total of 4660 patients with esophageal cancer underwent esophagectomy. Of these, 474 superficial ESCC patients were enrolled in the final analysis, with 322 patients in the training set and 142 patients in the validation set. The prevalence of LNM was 3.29% (5/152) for intramucosal cancer and increased to 26.40% (85/322) for submucosal cancer. Multivariate logistic analysis showed that tumor size, invasive depth, tumor differentiation, infiltrative growth pattern, tumor budding, and lymphovascular invasion were significantly correlated with LNM. A nomogram using these six variables showed good discrimination with an area under the ROC curve of 0.789 (95%CI: 0.737-0.841) in the training set and 0.827 (95%CI: 0.755-0.899) in the validation set. We developed a useful nomogram model to predict LNM risk for superficial ESCC patients which will facilitate additional decision-making in treating patients who undergo endoscopic resection.

The application of radiomics machine learning models based on multimodal MRI with different sequence combinations in predicting cervical lymph node metastasis in oral tongue squamous cell carcinoma patients.

The purpose of this study was to explore preliminary the performance of radiomics machine learning models based on multimodal MRI to predict the risk of cervical lymph node metastasis (CLNM) for oral tongue squamous cell carcinoma (OTSCC) patients. A total of 400 patients were enrolled in this study and divided into six groups according to the different combinations of MRI sequences. Group I consisted of patients with T1-weighted images (T1WI) and FS-T2WI (fat-suppressed T2-weighted images), group II consisted of patients with T1WI, FS-T2WI, and contrast enhanced MRI (CE-MRI), group III consisted of patients with T1WI, FS-T2WI, and T2-weighted images (T2WI), group IV consisted of patients with T1WI, FS-T2WI, CE-MRI, and T2WI, group V consisted of patients with T1WI, FS-T2WI, T2WI, and apparent diffusion coefficient map (ADC), and group VI consisted of patients with T1WI, FS-T2WI, CE-MRI, T2WI, and ADC. Machine learning models were constructed. The performance of the models was compared in each group. The machine learning model in group IV including T1WI, FS-T2WI, T2WI, and CE-MRI presented best prediction performance, with AUCs of 0.881 and 0.868 in the two sets. The models with CE-MRI performed better than the models without CE-MRI(I vs. II, III vs. IV, V vs. VI). The radiomics machine learning models based on CE-MRI showed great accuracy and stability in predicting the risk of CLNM for OTSCC patients.

A Novel LncRNA MASCC1 Regulates the Progression and Metastasis of Head and Neck Squamous Cell Carcinoma by Sponging miR-195.

The altered expression of long noncoding RNAs (lncRNAs) is associated with human carcinogenesis. We performed a high-throughput analysis of lncRNA expression in strictly selected pairs of metastatic head and neck squamous cell carcinoma (HNSCC) and non-metastatic HNSCC samples. We identified a novel lncRNA, which was highly expressed in metastatic HNSCC, named Metastasis Associated Squamous Cell Carcinoma 1 (MASCC1), for further study. Using qRT-PCR, we further compared MASCC1 expression in 60 HNSCC samples. The results show that high expression of MASCC1 in patients with HNSCC was related to poor prognosis. In vitro, MASCC1 knockdown (KD) inhibited HNSCC proliferation, migration, invasion, and tumor sphere formation, while promoting apoptosis. In vivo, MASCC1 KD inhibited HNSCC growth and lymph node metastasis. Mechanistically, MASCC1 acted as a competing endogenous RNA (ceRNA) by binding to miR-195, subsequently regulating the expression of Cyclin D1, BCL-2, and YAP1. Moreover, miR-195 overexpression rescued the effects of MASCC1 on the biological behaviors of HNSCC. Taken together, our results suggest that MASCC1 is a novel oncogene that can predict the prognosis of patients with HNSCC and is a potential therapeutic target for HNSCC intervention.