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@#Objective To investigate the effects of targeted silencing of CXCL5 on the related biological functions of laryngeal squamous cell carcinoma(LSCC)cell line AMC-HN-8,and analyze the regulation through TCGA database.Methods RNA-seq data related to LSCC were obtained from TCGA database,and the expression differences of CXCL5 gene in LSCC and the adjacent tissues were analyzed. Total 60 samples of LSCC and the adjacent tissues from January 2019 to December 2020 were selected from the First Hospital of Shanxi Medical University,and the expression of CXCL5 protein in LSCC tissues was detected by immunohistochemical staining. Human LSCC cell line AMC-HN-8 was cultured and the mRNA transcription level of CXCL5 in AMC-HN-8 cells was detected by qPCR. Two groups of SiRNA with high knock-down efficiency were screened,CCK8 assay was used to detect the cell proliferation,Transwell test was used to measure the cell invasion and migration,and flow cytometry was used to detect the cell cycle and apoptosis. The correlation between CXCL5and tumor immune invasion level of LSCC was analyzed by ssGSEA,and CXCL5 co-expression gene network was constructed and analyzed for GO and KEGG enrichment.Results Compared with the adjacent tissues and the cells in control group,the expression of CXCL5 in LSCC tissues and cells increased,which was consistent with the analysis of TCGA database;Inhibition of CXCL5 expression in AMC-HN-8 cells inhibited the proliferation,invasion and migration of tumor cells,and promoted the apoptosis through inhibiting the cell cycle in G1 phase;The immune cell scores in DC,neutrophils,NK and TH17 cells were different.Conclusion CXCL5gene is highly expressed in LSCC tissues,which might be one of the targets of LSCC targeted therapy.
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Abstract Objective: With the increasing incidence and mortality of laryngeal squamous cell carcinoma worldwide, researchers continue to search for novel prognostic factors and treatment methods for preventing early laryngeal squamous cell carcinoma from becoming advanced laryngeal squamous cell carcinoma. This study aims to determine if tumor budding is an independent risk factor associated with the survival of patients with laryngeal squamous cell carcinoma. Methods: 268 cases of laryngeal squamous cell carcinoma were studied, and tumor budding was analyzed for associations with clinicopathological features and clinical outcomes. Results: Tumor budding was divided into low-grade tumor budding (0-6/0.785mm2) and high-grade tumor budding (≥7/0.785 mm2) based on the results of the receiver operating characteristics curve analysis. Logistic regression analysis showed that smaller tumor cell nests, the low levels of tumor-infiltrating lymphocytes, and higher pathological T staging were the risk factors for high-grade tumor budding (p < 0.05). In the low-grade tumor budding group, there was no statistic difference in survival between patients without tumor budding and those with 1 -6/0.785 mm2 tumor budding. Multivariate survival analysis showed high-grade tumor budding (p < 0.001) was independent prognostic factors for disease-free survival and overall survival in laryngeal squamous cell carcinoma. High-grade tumor budding was also an independent prognostic factor for disease-free survival (p = 0.037) and overall survival (p = 0.009) in T1-2N0 laryngeal squamous cell carcinoma. Conclusions: Smaller tumor cell nests, the low levels of tumor-infiltrating lymphocytes, and higher pathological T staging were closely associated with high-grade tumor budding in laryngeal squamous cell carcinoma. High-grade tumor budding may be an adverse risk factor that affects not only the disease-free survival and overall survival of laryngeal squamous cell carcinoma patients but also the survival of T1-2N0 laryngeal squamous cell carcinoma patients. Level of Evidence: Level 4.
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Abstract Objective This study aimed to investigate the molecular mechanism of miR-150-5p regulating the malignant biological behavior of Human Epidermoid cancer cell (HEp-2) by targeting peptidyl-prolyl cis/trans isomerase NIMA-Interacting-1 (PIN1). Methods Firstly, qRT-PCR and Western blot were adopted to detect the expression levels of miR-150-5p and PIN1 in cancer tissue and paracancerous tissues of patients with LSCC, and those in human bronchial epithelial cells (16 HBE) and HEp-2. Next, the targeted relationship between miR-150-5p and PIN1 was assessed by bioinformatics website and dual-luciferase reporter assay, followed by their correlation analysis. Besides, after interfering with miR-150-5p or PIN1 expression in HEp-2 cells, CCK-8, cell colony formation assay, and transwell assay were utilized to detect the proliferation, viability, and invasion of cells, respectively. Subsequently, the protein levels of MMP-2, MMP-9, and EMT-related proteins in HEp-2 cells were checked by Western blot. Results Expression of miR-150-5p was down-regulated in LSCC tissues and HEp-2 cells. Moreover, miR-150-5p suppressed proliferation and invasion of HEp-2 cells, affected protein expression related to MMP and EMT, thereby inhibiting development of cancer. The expression of PIN1 was significantly increased in cancer tissues and HEp-2 cells, and there was a targeted relationship and negative correlation between miR-150-5p and PIN1 in cancer tissue. However, overexpression of PIN1 could reverse the effect of miR-150-5p on the proliferation and invasion of HEp-2 cells. Conclusion In a nutshell, there is a targeted relationship between PIN1 and miR-150-5p. Besides, miR-150-5p can inhibit the proliferation and invasion of HEp-2 cells by regulating the expression of PIN1. Level of evidence 3.
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Abstract Objectives We aimed to explore the heterogeneity and differentiation trajectories of epithelial cells and NK/T-cells in Laryngeal Squamous Cell Carcinoma (LSCC). Methods We downloaded the GSE150321 data set containing LSCC01 and LSCC02 samples single cell RNA data from Gene Expression Omnibus. The UMAP analysis was performed to identify the cell subpopulations and cell locations of subpopulations. Seurat package was used to analyze the differential expression of genes. The function of differential expression genes was analyzed using DAVID database. The monocle2 package was used to analyze differentiation trajectories. We used the CellChat package to observe the signaling pathways and ligand-receptor pairs for epithelial cells and NK/T-cells. Results All the LSCC cells were divided into 16 subpopulation that included 7 epithelial cell subsets, 3 T-cell subsets. The function analysis indicated that epithelial cells and NK/T-cells mainly participated in different process, such as cell cycle, immune response, and cell migration. Then, the results of differentiation trajectory indicated that the ability of migration, and the activation of the immune system increases, while the ability of apoptosis, and glucose metabolic process decreases as pseudotime. Migration-related epithelial cells act on all T-cells via the CNTN2-CNTN2 ligand-receptor pair, which suggested that CNTN2 might be an important biomarker for regulating migration of epithelial cells. Conclusions Our study characterized the heterogeneity of LSCC, which provided novel insights into LSCC and identified a new mechanism and target for clinical LSCC threapies. Evidence IV.
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OBJECTIVES@#Laryngeal squamous cell carcinoma (LSCC) is a common malignant tumor of head and neck. Screening of target genes for malignant tumor therapy is one of the focuses of cancer research, with proto-oncogene and tumor suppressor gene as the breakthrough. It has become an urgent need to find the target gene related to the treatment and prognosis of LSCC.This study aims to explore the role of Lin28B and C-myc in LSCC by detecting the expressions of these two proteins and analyze the correlation between the expression of Lin28B and C-myc and clinicopathological features and prognosis of LSCC.@*METHODS@#We detected the expression of Lin28B and C-myc proteins in 102 specimens of LSCC and 90 specimens of adjacent tissues by immunochemistry, and analyzed the correlation between Lin28B and C-myc protein expressions in LSCC as well as the correlation between the expressions of the two proteins and the clinicopathological features of LSCC. At the same time, the Kaplan-Meier method was used to analyze the relation between Lin28B and C-myc protein levels with the postoperative survival rate of LSCC patients.@*RESULTS@#The protein levels of Lin28B and C-myc in the LSCC tissnes were significantly higher than those in the adjacent tissues (both P<0.05),and there was a positive correlation between the expression of Lin28B and C-myc in LSCC (r＝0.476, P<0.05). The expression of Lin28B protein was closely related to age, lymph node metastasis, clinical stage, tumor size, and pathological differentiation of LSCC patients (all P<0.05). while the expression of C-myc protein was closely related to lymph node metastasis, clinical stage, tumor size, and pathological differentiation of LSCC patients (all P<0.05). A relevant survival analysis showed that in patients with higher level of Lin28B (P＝0.001) or C-myc protein (P<0.001), the postoperative survival rate was relatively low.@*CONCLUSIONS@#Lin28B and C-myc proteins are highly expressed in LSCC with a positive correlation. Furthermore, they are closely related to lymph node metastasis, clinical stage, tumor size, pathological differentiation and prognosis, suggesting that both Lin28B and C-myc might be involved in the occurrence and development of LSCC.
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Humans , Squamous Cell Carcinoma of Head and Neck , Proto-Oncogene Proteins c-myc/metabolism , Laryngeal Neoplasms/diagnosis , Carcinoma, Squamous Cell/genetics , Lymphatic Metastasis , Prognosis , Head and Neck Neoplasms , Biomarkers, Tumor/metabolism , RNA-Binding Proteins/geneticsABSTRACT
Abstract Objective: This study aimed to investigate the demographic and clinicopathological characteristics, and survival outcomes of subglottic Squamous Cell Carcinoma (SCC) based on the Surveillance, Epidemiology, and End Results (SEER) database. Methods: Demographic and clinicopathological information, including age, sex, race, tumor size, histologic grade, clinical/TNM stage, tumor invasion extent, Lymph Node Metastasis (LNM) extent, size of metastatic lymph nodes, LNM ratio and treatment data, of 842 subglottic SCC patients diagnosed between 1996 and 2016 were acquired. Kaplan-Meier survival analyses were performed to assess the effects of clinicopathological characteristics, treatment modalities, surgical procedures, and adjuvant therapies on overall survival and cancer-specific survival. Results: Subglottic SCC was more frequent among males aged 60-70 years, with low-grade but locally advanced lesions without local or distant metastases. Age and several primary tumor/LNM related variables were independent risk factors for overall survival and cancer specific survival. Advanced-stage and high-grade disease led to unfavorable prognosis. The most common treatment modality and surgical procedure were surgery plus radiotherapy and total laryngectomy, respectively. Surgery plus radiotherapy provided favorable 5-year survival outcomes, while total laryngectomy had the worst. Surgery plus adjuvant therapy showed better survival outcomes than surgery alone. Conclusion: This study confirmed the rarity of subglottic SCC. Patients with subglottic SCCs suffered poor prognosis especially for those with advanced-stage or high-grade lesions. The prognosis of subglottic SCC remained poor over the years, despite recent progress in cancer therapies. Surgery plus adjuvant therapy improved the survival outcome. Although larynx preservation surgery was beneficial for early-stage disease, total laryngectomy was favored for patients with advanced tumors. Level of evidence: Level 4.
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Abstract Introduction: Gelsolin protein has important cellular functions, including cell motility and apoptosis. Altered gelsolin expression has been reported in several types of neoplasms, but clinicopathological features of gelsolin are currently unclear in patients with laryngeal squamous cell carcinoma. Objectives: Our aim is to investigate the clinicopathological significance of gelsolin as a prognostic biomarker for laryngeal squamous cell carcinoma. Methods: Tissue specimens from 168 patients with laryngeal squamous cell carcinoma were immunohistochemically assessed for the Gelsolin expression. Prognostic significance of Gelsolin and its interaction with clinical parameters was analysed. Results: Gelsolin expression was confirmed in 70.2% of cases. Gelsolin expression is significantly associated with tumor stage, tumor grade, and locoregional recurrence. Kaplan-Meier survival curves revealed that Gelsolin expression inversely correlated with both disease-specific and overall survival. Conclusion: This research is the first to demonstrate that Gelsolin expression is associated with a poor prognosis in laryngeal squamous cell carcinoma. Gelsolin is a novel promising biomarker and attractive target for the treatment of laryngeal squamous cell carcinoma.
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Abstract Objective: This study aims to explore the effect and mechanism of miR-375 in Laryngeal Squamous Cell Carcinoma (LSCC) cell progression. Methods: LSCC cells (LSC-1 and TU177) were transfected with miR-375-mimic, miR-375-inhibitor or miR-375-mimic + oe-CST1. The expression of miR-375, CST1, MMP-2, and MMP-9 was measured. The effect of miR-375-mimic, miR-375-inhibitor or miR-375-mimic + oe-CST1 on cell biological functions, including cell proliferation, migration, invasion, and apoptosis, was also assessed. The potential relationship between CST1 and miR-375 was predicted by Jefferson software and validated by dual luciferase reporter gene assay. Results: Downregulated miR-375 expression was found in LSCC cells. Overexpression of miR-375 inhibited the viability and migration and promoted apoptosis of LSCC cells. Jefferson database and dual luciferase reporter gene assay confirmed that miR-375 directly targeted CST1. Over-expression of CST1 could reverse the anti-cancer effect of miR-375 overexpression in LSCC cells. Conclusion: Collected evidence showed that miR-375/CST1 axis was implicated in LSCC progression. Level of evidence: Level 3
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Objective To explore the influence of miR-200 c on the biological behavior of laryngeal carcinoma Hep-2 cells and determine whether miR-200 c exerts its biological function through peptidyl-prolyl cis/trans isomerase (PIN1) in laryngeal carcinoma. Methods A qRT-PCR assay for the expression of miR-200 c was performed in laryngeal carcinoma tissues. Hep-2 cells were transfected with miR-200 c related small RNAs. Transwell assay detected the migration ability of the cells. Immunofluorescence assay was used to detect the abnormal amplification of the centrosome. A dual luciferase reporter gene system was used to detect the binding ability between miR-200 c and PIN1. Western blotting detected the protein expression level of PIN1. Results The expression of miR-200 c in laryngeal carcinoma was significantly increased. miR-200 c inhibited the migration of Hep-2 cells and could weaken the abnormal amplification of centrosome.PIN1 was confirmed as one of the target genes of miR-200 c. miR-200 c inhibited the expression of PIN1 at the translation level and could inhibit Hep-2 cell migration and abnormal centrosome amplification by regulating PIN1. Conclusion miR-200 c can inhibit the migration ability of laryngeal carcinoma cells and abnormal centrosome amplification by regulating PIN1.
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OBJECTIVE@#To investigate the effect of sputum ubiquitin ligase (Cbl-b) gene known-down on the cytotoxicity of H9 T lymphocytes against human laryngeal squamous cancer Hep-2 cells and explore the underlying mechanism.@*METHODS@#CD4 T lymphocytes isolated from 12 patients with laryngeal squamous carcinoma and 12 healthy individuals were examined for Cbl-b mRNA expressions using RT-PCR. H9 T lymphocytes cultured in 96-well plates were transfected with Cbl-b siRNA via liposomes followed by treatment with an anti-IL-2 monoclonal antibody, with H9 T lymphocytes transfected with a scrambled sequence as the negative control. The expressions of Cbl-b mRNA and protein in the cells were detected using real-time fluorescent quantitative PCR and Western blotting, respectively. The killing effect of the treated T lymphocytes against Hep-2 cells was assessed using the cell counting kit (CCK-8). The positive expression rates of CD69 and CD25 on the surface of H9 T lymphocytes were determined using flow cytometry, and the levels of interleukin-2 (IL-2) and interferon-gamma (INF-γ) in the culture supernatants of H9 T lymphocytes were detected with ELISA.@*RESULTS@#The CD4 T lymphocytes from patients with laryngeal squamous carcinoma showed significantly increased Cbl-b mRNA level compared with those from healthy individuals ( < 0.05). Transfection of H9 T lymphocytes with Cbl-b siRNA significantly reduced the expression levels of Cbl-b mRNA and protein ( < 0.05), which were not significantly affected by subsequent treatment of the cells with the anti-IL-2 antibody (>0.05). At different target-effector ratios, the Cbl-b siRNA-transfected cells showed significantly higher Hep-2 cell killing rates and higher positivity rates of CD69 and CD25 expressions than the blank and negative control cells and the cells with both Cbl-b siRNA transfection and anti-IL-2 treatment ( < 0.05). Cbl-b silencing in H9 T lymphocytes resulted in significantly increased levels of IL-2 and INF-γ in the supernatant as compared with those in the blank and negative control groups ( < 0.05).@*CONCLUSIONS@#Cbl-b gene silencing effectively enhances the killing effect of H9 T lymphocytes against Hep-2 cells probably as the result of enhanced IL-2 secretion and T lymphocyte activation.
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Humans , Carcinoma, Squamous Cell , Genetics , Therapeutics , Gene Silencing , Laryngeal Neoplasms , Genetics , Therapeutics , Lymphocyte Activation , RNA, Small Interfering , T-LymphocytesABSTRACT
Objective@#To observe the expression and clinical significance of galectin-1 in Chinese laryngeal squamous cell carcinoma patients.@*Methods@#Immunohistochemical technique was used to test the galecin-1 protein expression in the 50 laryngeal squamous cell carcinoma patients and Western blot method was used to test the galecin-1 protein expression in the 3 of the patients. SAS 9.4 software was used to analyze the relationship between the galectin-1 protein and the clinical degrees, pathological grades and lymph node metastasis in all the cases.@*Results@#In the 50 laryngeal squamous cell carcinoma patients, the positive rate of galectin-1 protein was 74% (37/50). The expression of galectin-1 protein was correlated with the severity of clinical staging, pathological differentiation and lymph node metastasis.@*Conclusions@#High expression of galectin protein related with the occurrence and development of head and neck squamous cell carcinomas.
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Objective@#To investigate the effect of c-Met inhibitor AMG-102 on proliferation and radiosensitivity in laryngeal squamous carcinoma cells.@*Methods@#The effects of AMG-102 on proliferation and radiosensitivity of laryngeal squamous carcinoma cell lines Hep-2 and KBV200 were detected by 3-(4, 5-dimethy-2-thiazolyl)-2, 5-diphenyl-2H tetrazolium bromide (MTT) assay and colony formation assay, respectively. The apoptosis of Hep-2 and KBV200 cells was detected by flow cytometry. The expression levels of c-Met, phospho-Met (p-Met), cleaved caspase-3 and Akt/p-Akt, Erk/p-Erk were detected by Western blot. Specific small interfering RNA targeting c-Met or plasmid of c-Met were transfected into Hep-2 and KBV200 cells to investigate the cell sensitivity to AMG-102.@*Results@#Compared with KBV200 cells, Hep-2 cells were more sensitive to AMG-102 with IC50 of 14 and 9 μmol/L, respectively. The relative expression levels of c-Met and p-Met proteins in Hep-2 cells were 194.48±0.57 and 177.76±1.53, respectively, which were significantly higher than those in KBV200 cells (171.24±1.00 and 115.37±0.56, respectively, P<0.001 for both). Exogenous hepatocyte growth factor (HGF) was added to increase the expression level of p-Met protein in KBV200 cells. The results showed that AMG-102 significantly reduced the expression of p-Met in KBV200 cells treated with HGF (P<0.001). Compared with the dimethyl sulfoxide (DMSO) group, AMG-102 treatment combined with radiotherapy significantly increased the radiosensitivity of Hep-2 cells (SER=1.28, P<0.001). However, AMG-102 had little effect on the radiosensitivity of KBV200 cells (SER=1.18, P=0.002). Compared with the 4 Gy radiotherapy alone group and the 5 μmol/L of AMG-102 alone treatment group, the apoptosis rate of Hep-2 cells in the combined treatment group was significantly increased. Meanwhile, the expression level of cleaved caspase-3 protein was also markedly increased. However, there were no significant changes in the apoptotic rate and cleaved caspase-3 expression in each treatment group of KBV200 cells. Compared with DMSO treatment group, the expression levels of p-Met, p-Akt and p-Erk were significantly decreased in the 4 Gy radiotherapy group, 5 μmol/L of AMG-102 treatment group and combined treatment group of Hep-2 cells. And the levels of p-Met, p-Akt and p-Erk in the combined treatment group were significantly lower than those in the 4 Gy radiotherapy alone group and 5 μmol/L of AMG-102 treatment alone group. By contrast, in KBV200 cells, the expression of p-Met, p-Akt and p-Erk in each group was not changed. The relative expression of p-Met in Hep-2 cells before and after radiotherapy at 30 min, 1 h, 4 h, 8 h, 24 h were 99.89±0.61, 138.62±1.00, 163.07±5.00, 87.80±1.85, 90.67±0.65 and 94.09±1.41, respectively. The level of p-Met was slightly increased after radiotherapy at 30 min and 1 h (P<0.001 for all), whereas it was significantly decreased from 4 h to 24 h after radiotherapy (P<0.05 for all). By contrast, the expression of p-Met in KBV200 cells did not change with time after radiotherapy (P>0.05). The sensitivity of Hep-2 cells to AMG-102 was decreased after silencing of c-Met, while the sensitivity of KBV200 cells to AMG-102 was not significantly changed (P>0.05). Moreover, the radiosensitivity of Hep-2 cells in c-Met knockdown group had a slightly increasing trend (SER=1.07, P=0.068). After the treatment with 10 μmol/L of AMG-102, the proliferation rate of c-Met ectopically expressed KBV200 cells was 60.05%±3.23%, It was significantly lower than that of the blank control 90.08%±1.04% and siRNA negative control (90.12%±1.01%, P<0.001). The results suggested that the overexpression of c-Met in KBV200 cells increased the radiosensitivity to AMG-102, whereas depletion of c-Met resulted in resistance to AMG-102 in Hep-2 cells. Furthermore, the radiosensitivity of KBV200 cells that overexpressed c-Met showed a decreased trend (SER=0.7, P=0.005).@*Conclusions@#c-Met inhibitor AMG-102 has a significant inhibitory effect on the proliferation of c-Met overexpressing laryngeal squamous carcinoma cells, leading to increased radiosensitivity. It suggests that molecular targeted therapy against c-Met receptor is more effective in c-Met overexpressed subtype of laryngeal squamous cell carcinoma.
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@# Objective: To explore the expressions of melanoma antigen (MAGE) -A9, -A11 and Ki67 in laryngeal squamous cell carcinoma (LSCC) tissues, and to analyze their correlation with clinicopathological features and the prognosisof LSCC patients. Methods: A total of 73 pairs of LSCC tissuesand corresponding para-cancerous tissues resected from LSCC patients, who were treated at the Fourth Hospital of Hebei Medical University from 2012 to 2014,were collected for this study. At the same time, testicular tissues from 3 patients with prostate cancer after castration were selected as positive control. The protein expressions of MAGE-A9, MAGE-A11 and Ki67 in LSCC tissues and its para-cancerous tissues were detected by immunohistochemistry. Results: The expression rates of MAGEA9, MAGE-A11 protein and Ki67 in LSCC tissues were 47.94% (35/73), 49.32% (36/73) and 46.58% (34/73) respectively, which were significantly higher than those in para-cancerous tissues. The protein expressions of MAGE-A9 and MAGE-A11 were correlated with clinical stage and lymphatic metastasis of LSCC (P<0.05). The expression of Ki67LI was correlated with tumor size, clinical stage and lymphatic metastasis of LSCC (P<0.05). The correlation analysis showed that the expressions of MAGE-A9 and MAGE-A11 were positively correlated with Ki67 (r=0.258, P＝0.027; r=0.672, P=0.001). Kaplan-Meier survival curve analysis showed that the survival rates of patients with high expression of MAGE-A9 protein (P=0.009), MAGE-A11 protein (P=0.031) and Ki67LI (P=0.040) were significantly lower than those with low expressions. And the survival time of patients with both high expressions of MAGE-A9 and Ki67LI (P=0.001) or both high expressions of MAGE-A11 and Ki67 (P=0.001) was significantly shorter than that of patients with low expression (both or single). Univariate and multivariate Cox regression analysis further indicated that MAGE-A9 protein (P=0.028) and MAGE-A11 protein (P=0.042) were independent prognostic factors for overall survival of LSCC patients. Conclusion: MAGE-A9, MAGE-A11 and Ki67 are tumor-associated antigens of LSCC, which can be used as prognostic indicators for LSCC.
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Objective To investigate the expression of heparanase (HPA) and NF-E2 associated factor (NRF2) in laryngeal squamous cell carcinoma.Methods We collected 81 cases of laryngeal squamous cell carcinoma in our hospital from February 2015 to February 2017 as group A,and then selected 77 cases of polyp of vocal cord pathological specimens as group B.The expression of HPA was detected by immunohistochemistry,and the expression of NRF2 was detected by western blot.Results The positive expression rate of HPA and the expression of NRF in the group A and B were 81.48％,19.48％ and 0.844±0.113,0.202±0.094,the difference was statistically significant (P＜ 0.05).The positive expression rates of HPA in patients with lymph node metastasis and TNM stage Ⅲ to Ⅳ were 93.02％ and 94.87％,which were significantly higher than those without lymph node metastasis and stage Ⅰ to Ⅱ (P＜0.05).The positive expression rates of HPA in patients with low and middle differentiation were 93.75％ and 100.00％,which were significantly higher than those with high differentiation (P＜0.05).The expression of NRF2 in patients with lymph node metastasis and TNM stage Ⅲ to Ⅳ were 0.901± 0.122 and 0.885 ± 0.105,which significantly higher than those without lymph node metastasis and stage Ⅰ to Ⅱ (P＜0.05).The expression of NRF2 in patients with moderate and low differentiation were 0.854± 0.101 and 0.878 ± 0.099,which were significantly higher than patients with stage Ⅰ to Ⅱ (P＜0.05).Conclusion The expression of HPA and NRF2 in laryngeal squamous cell carcinoma are significantly increased,which are related to lymph node metastasis,TNM stage and pathological grade.
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Objective: To investigate the prognostic value of SIAH2 expression in laryngeal squamous cell carcinoma (LSCC). Methods: The qualitative expression of SIAH2 in 119 laryngeal tissues was studied by immunohistochemical staining. Western blot was used to examine the quantitative expression of SIAH2. Survival rates were calculated using the Kaplan-Meier method. Correlation between SIAH2 expression and LSCC patients'prognosis was analyzed by the Log-rank test. The Cox proportional hazards regression model was used to examine the independent predictive factors of LSCC. Results: The SIAH2 expression in LSCC (77.19%) was higher than that in the laryngeal atypical hyperplasia (53.13%) and normal laryngeal tissues (26.67%), and significant differences were observed (χ2=21.02, P=0.000). The expression of SIAH2 was significantly correlated to the histological grade, clinical stage, and lymph node metastasis (P<0.05). The relative expression of SIAH2 in normal laryngeal tissue (1.25±0.04), laryngeal atypical hyperplasia (1.38 ± 0.05), and LSCC (1.44±0.07) was observed to increase gradually (F=61.811, P<0.001). The 5-year survival rate of SIAH2 (+) and SIAH2 (-) patients was 18.18% and 58.33%, respectively (χ2=5.720, P=0.017), and the median survival time of SIAH2 (+) and SIAH2 (-) patients was 25 and 60 months, respectively (P<0.05 ). The multivariate regression analysis revealed that the higher expression of SIAH2 was an independent prognostic factor for the overall survival. Conclusions:SIAH2 may be involved in the tumorigenesis and progression of LSCC as an oncogene. Overexpression of the marker indicated poor prognosis of the disease, a finding which might allow SIAH2 to be used as a potential target gene for the treatment of LSCC.
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@#[Abstract] Objective: To search valuable candidate molecular markers for LSCC by screening and identifying differentially expressed long non-coding RNAs (lncRNAs) in metastatic laryngeal squamous cell carcinoma (LSCC) with high throughput gene microarray technique. Methods: Four pairs of LSCC tissues and corresponding para-cancer tissues that pathologically confirmed with lymph node metastasis were collected from Bio-sample lab of Otorhinolaryngology Department, the Second Hospital of Hebei Medical University. After total RNA extraction, the SBC-lncRNA (human 4x180k) chip assay was then applied to detect the differentially expressed lncRNAs and mRNAs, and Fold-change and Student's t-test methods were used to identify differentially expressed genes; the Fold Change (linear)≤0.5 or≥2.0, P<0.05 was used to identify the differentially expressed genes. The reliability of the chip results was confirmed by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Results: The gene expression profiles of metastatic LSCC tissues and corresponding para-cancer tissues were significantly different. There were 3 073 differentially expressed lncRNAs, including 1 967 up-regulated and 1 106 down-regulated lncRNAs in cancer tissues. There were 2 809 differentially expressed mRNAs, including 1 791 up-regulated and 1 018 down-regulated mRNAs in cancer tissues. The differentially expressed lncRNAs were mainly involved in cell proliferation and apoptosis, immune response biological process, and were associated with cytokine and cytokine receptor interaction, chemokine signaling pathway, cell cycle regulation, P53 signaling pathway, etc. In addition, 10 significantly differentially expressed lncRNAs were chosen and validated by qRT-PCR in 25 cases of LSCC tissues, and the results were in agree with microarray detection. Conclusions: There were obvious differences in lncRNAs expression between metastasis LSCC and corresponding para-cancer tissues; in-depth analysis of these differences may has important significance on clarifying the mechanisms of invasion and metastasis of LSCC, which can provide the theoretical basis for biomarker screening and effective targeted therapy for LSCC.·
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Actualmente se realiza un diagnóstico anual de 650.000 nuevos casos de carcinoma escamoso de cabeza y cuello en el mundo, siendo el carcinoma escamoso de laringe una patología neoplásica que compete al otorrinolaringólogo. La incidencia mundial del cáncer escamoso de laringe se estima en 3,9 por cada 100.000 habitantes con una mortalidad general de 2,0 por cada 100.000 habitantes. En Chile el registro de cáncer se realiza en base a los cinco registros poblacionales de cáncer que existen. No se tienen datos exactos respecto a incidencia y mortalidad por carcinoma escamoso de laringe, siendo la estimación de la incidencia de 1,2 casos por cada 100.000 habitantes y la estimación de mortalidad ajustada por edad de 0,7 casos por cada 100.000 habitantes. Se han descrito diversos factores de riesgo ambientales y estilos de vida para este cáncer, por lo tanto, las estrategias de prevención primaria en salud son claves a la hora de generar un impacto en la incidencia del carcinoma escamoso de laringe.
The annual diagnosis of head and neck squamous cell carcinoma is 650,000 new cases. The laryngeal carcinoma is a malignant disease that should include an otolaryngologist in its evaluation. The global incidence of laryngeal carcinoma is estimated at 3.9 per 100,000 inhabitants with an overall mortality rate of 2.0 per 100,000 inhabitants. In Chile the cancer registry is based on the five population cancer registries that exist. There is no accurate data on incidence and mortality from laryngeal carcinoma, being an estimated incidence of 1.2 cases per 100,000 inhabitants and an age-adjusted mortality of 0.7 cases per 100.00 inhabitants. There have been described various environmental risk factors and lifestyles for this cancer, therefore, primary prevention strategies are key to generate an impact on the incidence of larynx carcinoma.
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Humans , Carcinoma, Squamous Cell/mortality , Laryngeal Neoplasms/mortality , Carcinoma, Squamous Cell/epidemiology , Carcinoma, Squamous Cell/prevention & control , Chile/epidemiology , Diseases Registries , Incidence , Laryngeal Neoplasms/epidemiology , Laryngeal Neoplasms/prevention & control , Risk FactorsABSTRACT
Objective To explore the FOXP3-related mechanism underlying head and neck squamous cell carcinoma.Methods We used cbioportal to identify the co-expressed genes of FOXP3 in 279 samples from head and neck squamous cell carcinoma in TCGA database.We used String database to establish the co-expression network of FOXP3.The function of co-expression network was identified through DAVID database.We used miRTarBase and StarBase database to screen the microRNA,lncRNA and circRNA that regulate FOXP3.Finally,Cytoscape software was used to establish FOXP3-related ceRNA network.Results We found 950 FOXP3 related co-expressed gene.(Spearman score over 0.5) These genes were enriched in immune response including T cell,leukocyte and lymphocyte activation.CeRNA network revealed that 2 microRNAs (i.e.,miR-31-5p and miR-210-3p),42 lncRNAs (e.g.,XIST,TUG1,JRK and LINC00473) and 31 circRNAs (e.g.,ZNF223 _hsa_ circ_ 000898 and ISY1 _hsa _circ _001090) could regulate FOXP3.Conclusion We established FOXP3-related ceRNA network and identified 42 lncRNAs and 31 circRNAs that regulate FOXP3.The data generated from this study could provide a new cut point in research and treatment of head and neck squamous cell carcinoma.
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Non-coding RNAs (ncRNAs) are a class of RNAs that do not encode proteins, including microRNAs (miRNAs), long non-cod-ing RNAs (lncRNAs), and circular RNAs (circRNAs). The ncRNAs play a vital role not only in the regulation of biological processes but al-so in the development of a variety of diseases, including cancer. The ncRNAs show significant clinical value in the diagnosis, prognosis, and therapy of laryngeal cancer (LC). Laryngeal squamous cell carcinoma (LSCC), the most common pathological type of LC, shows a re-cent trend in increasing incidences with a serious impact on human health and quality of life. In this paper, we summarize the research progress in recent years, and review the role of miRNAs, lncRNAs, and circRNAs in the development and progression of LC.
ABSTRACT
@#Laryngeal SCCA usually presents with hoarseness when the glottis is involved, dysphagia if the supraglottis is involved, and difficulty of breathing and stridor in subglottic invovlement. A neck mass as an initial presentation of laryngeal carcinoma is commonly linked to the involvement of the supraglottis due to its rich lymphatic drainage. About 70% of supraglottic tumours present with advanced disease (stages III-IV),1 while 75% of glottic tumours present with localized disease (stages I-II).1 Smoking and alcohol consumption are considered highly significant etiologic factors but evidence has suggested a possible role for human papilloma virus (HPV) infection, ras oncogene activation, and gastroesophageal reflux as well.2 To the best of our knowledge, laryngeal squamous cell carcinoma has not been associated with herpes simplex virus (HSV). We report a case of laryngeal squamous cell carcinoma with an unusual presentation and peculiar histopathology, and discuss its potential association with herpes simplex virus.