Tumor Suppressive Circular RNA-102450: Development of a Novel Diagnostic Procedure for Lymph Node Metastasis from Oral Cancer.
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ABSTRACT:
SUBMITTER: Ando T
PROVIDER: S-EPMC8616294 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Circular RNAs (circRNAs) appear important in tumor progression of colon cancer (CC). We identified an extensive catalog of circRNAs in 181 chemonaive stage I/II colon tumors, who underwent curative surgery between 2007 and 2014. We identified circRNAs from RNAseq data, investigated common biology related to circRNA expression, and studied the association between circRNAs and relapse status, tumor stage, consensus molecular subtypes (CMS), tumor localization and microsatellite instability (MSI). We identified 2606 unique circRNAs. 277 circRNAs (derived from 260 genes) were repeatedly occurring in at least 20 patients of which 153 showed a poor or even negative (R < 0.3) correlation with the expression level of their linear gene. The circular junctions for circSATB2, circFGD6, circKMT2C and circPLEKHM3 were validated by Sanger sequencing. Multiple correspondence analysis showed that circRNAs were often co-expressed and that high diversity in circRNAs was associated with favorable disease-free survival (DFS), which was confirmed by Cox regression analysis (Hazard Ratio (HR) 0.60, 95% CI 0.38-0.97, p = 0.036). Considering individual circRNAs, absence of circMGA was significantly associated with relapse, whereas circSATB2, circNAB1, and circCEP192 were associated with both MSI and CMS. This study represents a showcase of the potential clinical utility of circRNAs for prognostic stratification in patients with stage I-II colon cancer and demonstrated that high diversity in circRNAs is associated with favorable DFS.
| S-EPMC8071322 | biostudies-literature
Project description:Oral microbiota can alter cancer susceptibility and progression by modulating metabolism and inflammation. We assessed the association between the oral microbiome and lymph node (LN) metastasis in oral squamous cell carcinoma (OSCC). We collected a total of 54 saliva samples from patients with OSCC before surgery. LN metastasis was assessed based on postoperative pathological examination. We used QIIME2, linear discriminant analysis effect size (LEfSe), and PICRUSt2 methods to analyze microbial dysbiosis. A random forest classifier was used to assess whether the oral microbiome could predict LN metastasis. Among the 54 OSCC samples, 20 had LN metastasis, and 34 had no evidence of metastasis. There was a significant difference in β-diversity between the metastasis and no metastasis groups. Through LEfSe analysis, the metastasis group was enriched in the genera Prevotella, Stomatobaculum, Bifidobacterium, Peptostreptococcaceae, Shuttleworthia and Finegoldia. Pathways related to signal peptidase II were predominant in the no metastasis group. The RF model showed a modestly high accuracy for predicting metastasis. Differences in microbial community composition and functions were observed in the oral microbiome of patients with OSCC with and without LN metastasis. However, the finding that specific taxa may be associated with LN metastasis should be verified in a further prospective study.
| S-EPMC8633319 | biostudies-literature
Project description:Neck lymph node metastasis (LN+) is one of the most significant prognostic factors affecting 1-in-2 patients diagnosed with oral squamous cell carcinoma (OSCC). The different LN outcomes between clinico-pathologically similar primary tumors suggest underlying molecular signatures that could be associated with the risk of nodal disease development. MicroRNAs (miRNAs)are short non-coding molecules that regulate the expression of their target genes to maintain the balance of cellular processes. A plethora of evidence has indicated that aberrantly expressed miRNAs are involved in cancers with either an antitumor or oncogenic role. In this study, we characterized miRNA expression among OSCC fresh-frozen tumors with known outcomes of nodal disease (82 LN+, 76 LN0). We identified 49 differentially expressed miRNAs in tumors of the LN+ group. Using penalized lasso Cox regression, we identified a group of 10 miRNAs of which expression levels were highly associated with nodal-disease free survival. We further reported a 4-miRNA panel (miR-21-5p, miR-107, miR-1247-3p, and miR-181b-3p) with high accuracy in discriminating LN status, suggesting their potential application as prognostic biomarkers for nodal disease.
| S-EPMC7289532 | biostudies-literature
Project description:BACKGROUND: We previously identified tumor-reactive lymphocytes in the first lymph nodes that drain the primary tumor. In this study, we performed lymphatic mapping to investigate the possibility of finding the first lymph nodes that drain metastases, and of learning whether these lymph nodes contained tumor-reactive lymphocytes suitable for adoptive immunotherapy. METHODS: Nineteen patients were studied. The primary tumor site was colorectal cancer in seven patients, malignant melanoma in four, ovarian cancer and breast cancer in two, and one each with pancreatic cancer, cholangiocarcinoma, leiomyosarcoma, and squamous cellular cancer of the tongue. By injection of Patent blue dye or radioactive tracers around the metastases, we identified draining lymph nodes from liver metastases (n = 9), intra-abdominal local recurrences (n = 3), and regional lymph node metastases (n = 7). In six patients, a preoperative lymphoscintigraphy was performed. RESULTS: We located the first draining lymph node or nodes from metastases or local recurrences; we named them "metinel nodes." Lymphocytes from the metinel nodes proliferated, showed clonal expansion, and produced interferon gamma (via in vitro expansions on stimulation with tumor homogenate) and interleukins, all of which demonstrate the characteristics of tumor-reactive lymphocytes. Eight of the nineteen patients received immunotherapy on the basis of tumor-reactive T cells derived from the metinel nodes. CONCLUSIONS: We demonstrate that it is possible to locate the first lymph nodes draining subcutaneous, lymphatic, and visceral metastases, the so-called metinel nodes. Metinel node-derived lymphocytes may be used to treat disseminated solid cancer, and clinical trials should evaluate the effect of such treatment.
| S-EPMC2277445 | biostudies-other
Project description:Lymph nodes are important peripheral immune organs in which numerous important immune responses occur. During the process of lymphatic metastasis, lymph nodes are also sites through which tumor cells must pass. Therefore, it is essential to develop a drug delivery system that can specifically transfer immunostimulatory medicine into lymph nodes to block lymphatic metastasis. Here, we developed a nucleic acid drug delivery system containing cationic agarose (C-agarose) and CpG oligodeoxynucleotides. C-agarose has a high affinity for Siglec-1 on the surface of lymph node sinus macrophages, which have a high specificity for targeting lymph nodes. Subcutaneous implantation of C-agarose+CpG gel caused the accumulation of CpG in the lymph node sinus macrophages and generated antitumor immune responses in the lymph node. C-agarose+CpG gel treatment decreased the metastasis size in the tumor-draining lymph node (TDLN) and lung metastatic nodules and suppressed tumor growth in both a mouse 4T1 breast cancer model and a B16F10 melanoma model. On this basis, this study proposes a nonsurgical invasive lymph node targeting immunotherapy concept that may provide a new approach for antitumor metastasis.
| S-EPMC6529739 | biostudies-literature
Project description:ObjectiveTo develop and validate a novel RNA-seq-based nomogram for preoperative prediction of lymph node metastasis (LNM) for patients with oral squamous cell carcinoma (OSCC).MethodsRNA-seq data for 276 OSCC patients (including 157 samples with LNM and 119 without LNM) were downloaded from TCGA database. Differential expression analysis was performed between LNM and non-LNM of OSCC. These samples were divided into a training set and a test set by a ratio of 9 : 1 while the relative proportion of the non-LNM and LNM groups was kept balanced within each dataset. Based on clinical features and seven candidate RNAs, we established a prediction model of LNM for OSCC using logistic regression analysis. Tenfold crossvalidation was utilized to examine the accuracy of the nomogram. Decision curve analysis was performed to evaluate the clinical utility of the nomogram.ResultsA total of 139 differentially expressed RNAs were identified between LNM and non-LNM of OSCC. Seven candidate RNAs were screened based on FPKM values, including NEURL1, AL162581.1 (miscRNA), AP002336.2 (lncRNA), CCBE1, CORO6, RDH12, and AC129492.6 (pseudogene). Logistic regression analysis revealed that the clinical N stage (p < 0.001) was an important factor to predict LNM. Moreover, three RNAs including RDH12 (p value < 0.05), CCBE1 (p value < 0.01), and AL162581.1 (p value < 0.05) could be predictive biomarkers for LNM in OSCC patients. The average accuracy rate of the model was 0.7661, indicating a good performance of the model.ConclusionOur findings constructed an RNA-seq-based nomogram combined with clinicopathology, which could potentially provide clinicians with a useful tool for preoperative prediction of LNM and be tailored for individualized therapy in patients with OSCC.
| S-EPMC7479460 | biostudies-literature
Project description:Circular RNAs (circRNAs) have been identified as a novel class of non-conding RNAs, which are stable and have covalently single-stranded loop configuration.With the improvement of RNA-sequencing and bioimofrmatics, numerous dysregulated expression of circRNAs has been identified in kinds of physiological and pathological processes, especially in tumorigenesis. To date, however, the discovery of cirtical circRNA abnormalities, as well as their functions and underlying mechanisms, in the progress of esophageal squamous cell carcinoma (ESCC), is still unknown.
2021-08-31 | GSE150476 | GEO
Project description:BackgroundThe authors aimed to create a novel model to predict lymphatic metastasis in thymic epithelial tumors.MethodsData of 1018 patients were collected from the Surveillance, Epidemiology, and End Results database from 2004 to 2015. To construct a nomogram, the least absolute shrinkage and selection operator (LASSO) regression model was used to select candidate features of the training cohort from 2004 to 2013. A simple model called the Lymphatic Node Metastasis Risk Scoring System (LNMRS) was constructed to predict lymphatic metastasis. Using patients from 2014 to 2015 as the validation cohort, the predictive performance of the model was determined by receiver operating characteristic (ROC) curves.ResultsThe LASSO regression model showed that age, extension, and histology type were significantly associated with lymph node metastasis, which were used to construct the nomogram. Through analysis of the area under the curve (AUC), the nomogram achieved a AUC value of 0.80 (95 % confidence interval [Cl] 0.75-0.85) in the training cohort and 0.82 (95 % Cl 0.70-0.93) in the validation cohort, and had closed calibration curves. Based on the nomogram, the authors constructed the LNMRS model, which had an AUC of 0.80 (95 % Cl 0.75-0.85) in the training cohort and 0.82 (95% Cl 0.70-0.93) in the validation cohort. The ROC curves indicated that the LNMRS had excellent predictive performance for lymph node metastasis.ConclusionThis study established a nomogram for predicting lymph node metastasis. The LNMRS model, constructed to predict lymphatic involvement of patients, was more convenient than the nomogram.
| S-EPMC8677650 | biostudies-literature
Project description:BackgroundThe aims of this study were to determine intra (ILVD) and peritumoral (PLVD) lymphatic vessel density (LVD), and to investigate the relationship of LVD with occult metastasis and prognosis.MethodsEighty-seven oral squamous cell carcinomas, in clinical stages I or II, arising in the tongue or floor of the mouth were stained with podoplanin. Lymphatic vessels were quantified in intra and peritumoral areas by sequential analysis and hot spot evaluation. Associations of the ILVD and PLVD with clinicopathologic parameters were determined by Chi-square or Fisher's exact test. The 5 and 10-year survival rates were calculated by the Kaplan-Meier and compared using the log-rank test.ResultsNo significant association was observed between ILVD or PLDV and clinicopathologic variables including occult lymph node metastasis, or clinical follow-up. However, ILVD showed a significant association with regional recurrence (p = 0.040). The perineural invasion was associated with PLVD (p = 0.041). Disease-specific (p = 0.044) and disease-free survivals (p = 0.016) had significant association with PLVD.ConclusionsThe intra or peritumoral lymphatic vessel density had no predictive value for occult lymph node metastasis in the early stages of oral cancer arising in the tongue or floor of mouth.
| S-EPMC7948342 | biostudies-literature
Project description:BackgroundSentinel lymph node metastasis is a common and early event in the metastatic process of head and neck squamous cell carcinoma (HNSCC) and is the most powerful prognostic factor for survival of HNSCC patients. 3-O-acetyloleanolic acid (3AOA), a pentacyclic triterpenoid compound isolated from seeds of Vigna sinensis K., has been reported to have potent anti-angiogenesis and anti-tumor activities. However, its effects on tumor-related lymphangiogenesis and lymph node metastasis are not yet understood.MethodsThe in vitro inhibitory effects of 3AOA on VEGF-A-induced lymphangiogenesis were investigated via in vitro experiments using mouse oral squamous cell carcinoma (SCCVII) cells and human lymphatic microvascular endothelial cells (HLMECs). The in vivo inhibitory effects of 3AOA on VEGF-A-induced lymphangiogenesis and sentinel lymph node metastasis were investigated in an oral cancer sentinel lymph node (OCSLN) animal model.Results3AOA inhibited tumor-induced lymphangiogenesis and sentinel lymph node metastasis in an OCSLN animal model, and reduced expression of VEGF-A, a lymphangiogenic factor in hypoxia mimetic agent CoCl2-treated SCCVII cells. 3AOA inhibited proliferation, tube formation, and migration of VEGF-A-treated HLMECs. The lymphatic vessel formation that was stimulated in vivo in a by VEGF-A Matrigel plug was reduced by 3AOA. 3AOA suppressed phosphorylation of vascular endothelial growth factor (VEGFR) -1 and - 2 receptors that was stimulated by VEGF-A. In addition, 3AOA suppressed phosphorylation of the lymphangiogenesis-related downstream signaling factors PI3K, FAK, AKT, and ERK1/2. 3AOA inhibited tumor growth, tumor-induced lymphangiogenesis, and sentinel lymph node metastasis in a VEGF-A-induced OCSLN animal model that was established using VEGF-A overexpressing SCCVII cells.Conclusion3AOA inhibits VEGF-A-induced lymphangiogenesis and sentinel lymph node metastasis both in vitro and in vivo. The anti-lymphangiogenic effects of 3AOA are probably mediated via suppression of VEGF-A/VEGFR-1 and VEGFR-2 signaling in HLMECs, and can be a useful anti-tumor agent to restrict the metastatic spread of oral cancer.
| S-EPMC6034267 | biostudies-literature