Objective:Through integrated bioinformatics analysis,the goal of this work was to find new,characterised N7-methylguanosine modification-related long non-coding RNAs(m7G-lncRNAs)that might be used to predict the progn...Objective:Through integrated bioinformatics analysis,the goal of this work was to find new,characterised N7-methylguanosine modification-related long non-coding RNAs(m7G-lncRNAs)that might be used to predict the prognosis of laryngeal squamous cell carcinoma(LSCC).Methods:The clinical data and LSCC gene expression data for the current investigation were initially retrieved from the TCGA database&sanitised.Then,using co-expression analysis of m7G-associated mRNAs&lncRNAs&differential expression analysis(DEA)among LSCC&normal sample categories,we discovered lncRNAs that were connected to m7G.The prognosis prediction model was built for the training category using univariate&multivariate COX regression&LASSO regression analyses,&the model’s efficacy was checked against the test category data.In addition,we conducted DEA of prognostic m7G-lncRNAs among LSCC&normal sample categories&compiled a list of co-expression networks&the structure of prognosis m7G-lncRNAs.To compare the prognoses for individuals with LSCC in the high-&low-risk categories in the prognosis prediction model,survival and risk assessments were also carried out.Finally,we created a nomogram to accurately forecast the outcomes of LSCC patients&created receiver operating characteristic(ROC)curves to assess the prognosis prediction model’s predictive capability.Results:Using co-expression network analysis&differential expression analysis,we discovered 774 m7G-lncRNAs and 551 DEm7G-lncRNAs,respectively.We then constructed a prognosis prediction model for six m7G-lncRNAs(FLG−AS1,RHOA−IT1,AC020913.3,AC027307.2,AC010973.2 and AC010789.1),identified 32 DEPm7G-lncRNAs,analyzed the correlation between 32 DEPm7G-lncRNAs and 13 DEPm7G-mRNAs,and performed survival analyses and risk analyses of the prognosis prediction model to assess the prognostic performance of LSCC patients.By displaying ROC curves and a nomogram,we finally checked the prognosis prediction model's accuracy.Conclusion:By creating novel predictive lncRNA signatures for clinical diagnosis&therapy,our findings will contribute to understanding the pathogenetic process of LSCC.展开更多
Summary: To investigate the expression of hypoxia inducible factor-1 alpha (HIF-1α) and its relationship to apoptosis and proliferation in laryngeal squamous cell carcinoma (LSCC), immunohistochemical method was used...Summary: To investigate the expression of hypoxia inducible factor-1 alpha (HIF-1α) and its relationship to apoptosis and proliferation in laryngeal squamous cell carcinoma (LSCC), immunohistochemical method was used to detect the expression of HIF-1α and PCNA. Tunnel technique was used to detect in situ cell apoptosis in LSCC. Our results showed that the expression of HIF-1α was related to the clinical stages of cancer and lymph node metastasis (P<0.05). The relationship between HIF-1α and PCNA was statistically significant (P<0.05) and no relationship was found between HIF-1α and apoptosis (P>0.05) It is concluded that HIF-1α plays a role in the carcinogenesis of laryngeal carcinoma and is correlated with proliferation, but bears no relationship with the apoptosis of tumor cells in LSCC.展开更多
n order to study the expressions of vascular endothelial growth factor (VEGF) and cyclooxygenase-2 (COX-2) in human laryngeal squamous cell carcinoma (LSCC) and its significance, the expression of VEGF mRNA and ...n order to study the expressions of vascular endothelial growth factor (VEGF) and cyclooxygenase-2 (COX-2) in human laryngeal squamous cell carcinoma (LSCC) and its significance, the expression of VEGF mRNA and COX-2 mRNA in 62 cases of LSCC and 54 adjacent noncancerous laryngeal tissues and 9 normal human laryngeal mucous tissues was detected by using techniques of semi-quantitative RT-PCR. It was found that the expression level of VEGF and COX-2 mRNA was significantly increased in LSCC as compared with that in the normal human laryngeal mucous tissues (both P〈0. 01), and the expression level of VEGF and COX-2 mRNA were significantly increased in stage Ⅲ+ Ⅳtissues of LSCC as compared with the stage Ⅰ + Ⅱ tissues of LSCC (P 〈0.01). There was a high positive correlation between VEGF and COX-2 expression in LSCC (r= 0. 756,P〈0.01). These data raise the possibility that VEGF and COX-2 may play key roles in the growth, invasion and metastasis of LSCC.展开更多
Objective:To evaluate the short-term effects of neoadjuvant chemotherapy with pingyangmycin(PYM)in the treat-ment of laryngeal squamous cell carcinoma.Methods:24 cases of laryngeal squamous cell carcinoma were treated...Objective:To evaluate the short-term effects of neoadjuvant chemotherapy with pingyangmycin(PYM)in the treat-ment of laryngeal squamous cell carcinoma.Methods:24 cases of laryngeal squamous cell carcinoma were treated with PYM before the operation,and the surgeries were undergone within one week after neoadjuvant chemotherapy.PCNA,p53,Bcl-2 and CD44v6 were detected in the specimens of tumor,retreated tumor and normal tissue using immunohistochemical methods.Results:Apoptosis could be detected more often in specimens with tumor and retreated tumor after chemotherapy than that before.The expression of PCNA,p53,Bcl-2 and CD44v6 in tumor tissue after neoadjuvant chemotherapy with PYM was weaker than that before the chemotherapy.There was significant difference in the positive ratio of PCNA,p53,Bcl-2 and CD44v6 be-tween retreated tumor and tumor.Conclusion:After neoadjuvant chemotherapy with PYM,a large number of tumor cells died.The amplification and metastasis of tumor were suppressed by neoadjuvant chemotherapy with PYM.展开更多
OBJECTIVE To investigate the prognostic value of measuring Ki67 and VEGF expression in laryngeal squamous cell carcinoma (LSCC). METHODS The expression of Ki67 and VEGF in 32 LSCC tissues was studied by immunohistoche...OBJECTIVE To investigate the prognostic value of measuring Ki67 and VEGF expression in laryngeal squamous cell carcinoma (LSCC). METHODS The expression of Ki67 and VEGF in 32 LSCC tissues was studied by immunohistochemical staining. Of these cases, 5 recurred (recurrent group), 3 cases metastasized (metastatic group), 8 cases died (deceased group) and 24 cased survived (survival group) over a 3 year period of follow-up after their operation. RESULTS The expression of Ki67 and VEGF in the deceased group was higher compared to that in the survival group (P<0.01). Overexpression of Ki67 was found in the recurrent group and in the metastatic group (P< 0.05). VEGF expression was higher in the recurrent group than in the non recurrent group (P<0.05). With Cox-regression of multivariate analysis, Ki67 (RR:3.236; P=0.001), the clinical T stage (RR: 1.382; P=0.029) and metastasis in lymph nodes (RR:0.316; P=0.033) were shown to be independent prognostic factors for survival of LSCC patients. CONCLUSION Ki67 and VEGF expression is related to the prognosis of LSCC. Overexpression of the 2 markers indicated poor prognosis of the disease, a finding which might be helpful for the treatment of laryngocar-cinoma.展开更多
Background: Despite recent advances in clinical management of laryngeal squamous cell carcinoma (LSCC), the overall 5-year survival continues to be poor. Consequently, biomarkers of treatment response will need to be ...Background: Despite recent advances in clinical management of laryngeal squamous cell carcinoma (LSCC), the overall 5-year survival continues to be poor. Consequently, biomarkers of treatment response will need to be identified. Proteomic strategies are one way to attempt to identify such biomarkers. Methods: The Medline, Embase and Cochrane Library databases were systematically searched until 1st March 2014 using the terms “larynx”, “squamous cell carcinoma”, “proteomic”, and “biomarker”. Articles which met inclusion criteria were assessed for the type of biomarker investigated, the proteomic technique used, and whether any validation had been performed. Results: Six studies identified biomarkers, including UCRP, ceramides, uPA, MT1-MMP, stratifin, transferrin, albumin, S100 calcium-binding protein A9, stathmin, enolase, PLAU, IGFBP7, MMP14, THBS1, and transthyretin. Transferrin was the only biomarker to appear in more than one study. Conclusions: Our review identified several potential biomarkers of outcome in LSCC. Well designed studies will need to further validate their use in the future.展开更多
Laryngeal squamous cell carcinoma(LSCC) remains a highly morbid and fatal disease. Historically, it has been a model example for organ preservation and treatment stratification paradigms. Unfortunately, survival for L...Laryngeal squamous cell carcinoma(LSCC) remains a highly morbid and fatal disease. Historically, it has been a model example for organ preservation and treatment stratification paradigms. Unfortunately, survival for LSCC has stagnated over the past few decades. As the era of next-generation sequencing and personalized treatment for cancer approaches, LSCC may be an ideal disease for consideration of further treatment stratification and personalization. Here, we will discuss the important history of LSCC as a model system for organ preservation, unique and potentially targetable genetic signatures of LSCC, and methods for bringing stratified, personalized treatment strategies to the 21^(st) century.展开更多
OBJECTIVE To investigate the clinical and functional association of mi R-194 in human laryngeal squamous cell carcinoma(LSCC).METHODS Cell growth was measured by MTT assay.Cel cycle distribution was detected using PI ...OBJECTIVE To investigate the clinical and functional association of mi R-194 in human laryngeal squamous cell carcinoma(LSCC).METHODS Cell growth was measured by MTT assay.Cel cycle distribution was detected using PI staining by flow cytometric analysis.Cell migration and invasion were examined by wound healing assay and transwell assay.The 3′-UTR activity was detected by luciferase assay.The expression level of proteins and mR NA were analysed by Western blotting,immunohistochemistry and q RT-PCR.Mouse xenograft model was established to observe the tumor growth in vivo.RESULTS The expression level of miR-194 is significantly lower in clinical LSCC tissues compared with normal tissues,and is correlated with lymph node metastasis and TNM stage.Kaplan-Meier analysis shows that high miR-194 expression predicts a favorable outcome for LSCC patients.Functional assays show that enforced expression of mi R-194 inhibits the growth,migration,invasion and drug-resistance of LSCC cells.Moreover,Wee1 is identified as a novel functional target of mi R-194.Exogenous expression of Wee1 protein in mi R-194-over expressing cells partially reverses the suppressive effects of mi R-194 on LSCC cells.In addition,Wee1 was abnormally overexpressed in clinical LSCC tissues,and its protein levels were inversely correlated with miR-194 expression.High Wee1 protein level was also associated with TNM stage,lymph node metastasis and poor prognosis.CONCLUSION Our study provides new sights into the role of miR-194/Wee1 axis in LSCC,and suggests a novel miR-194/Wee1-based clinical intervention target for LSCC patients.展开更多
Objective:Laryngeal squamous cell carcinoma(LSCC) is a common malignant tumor in Northeast China and is frequently associated with well-established risk factors like smoking and alcohol abuse.Human papilloma virus...Objective:Laryngeal squamous cell carcinoma(LSCC) is a common malignant tumor in Northeast China and is frequently associated with well-established risk factors like smoking and alcohol abuse.Human papilloma virus(HPV) is an epitheliotropic oncogenic virus that has been detected in a variety of head and neck tumors including LSCC.This retrospective study was to investigate the prevalence of HPV infection in patients with LSCC.Methods:In situ hybridization was performed in 99 patients with LSCC to detect the expression of HPV-16 E6 mRNA.Results:The positive rate of HPV16 E6 mRNA was 36.36%(36/99) in laryngeal squamous cell carcinoma(LSCC),whereas only 3 of 50(6%) specimens of the normal laryngeal mucosa as a control group showed positive results(P0.05).Additionally,there was no corelation between HPV16 and age,gender,clinical stage,nodal status and tumor site(P0.05).Conclusion:The results suggest that the increased prevalence of HPV infection compared to normal laryngeal mucosa and the fact that high-risk HPV types(especially type 16) were the most frequently identified do not allow the exclusion of HPV as a risk factor in laryngeal squamous cell carcinoma.However,their clinical value remains to be further investigated.展开更多
Objective: To study the correlation between Ki67 and vascular endothelial growth factor(VEGF) and the significance of their expression in laryngeal squamous cell carcinoma(LSCC). Methods: The expressions of Ki67...Objective: To study the correlation between Ki67 and vascular endothelial growth factor(VEGF) and the significance of their expression in laryngeal squamous cell carcinoma(LSCC). Methods: The expressions of Ki67 and VEGF in 40 cases of LSCC and 5 cases of normal laryngeal mucosa were examined by immunohistochemical staining. Results: The expression levels of Ki67 and VEGF in LSCC tissue were higher than in normal laryngeal mucosa (Ki67: P〈0.001, VEGF: P〈0.001). The two indexes' levels in patients of different age or different sex had no significant difference (P〉0.05). They were higher in LSCC with metastasis of lymph nodes than in patients without metastasis (Ki67: P=0.034, VEGF: P=0.006). The expressions of the two genes elevated correspondingly along with the development of LSCC T stage (P〈0.05). In addition, correlation analysis indicated that the expression of Ki67 had a positive correlation with VEGF in LSCC(r=0.823, P〈0.01). Conclusion: Ki67 and VEGF are objective indexes for the biological behavior of LSCC, and they might be helpful to the diagnosis, treatment and prognosis of laryngocarcinoma.展开更多
Objective: Patients with head and neck cancer often suffer from malnutrition. This study aims to investigate the influence of body mass index(BMI) on the prognosis of laryngeal squamous cell carcinoma(LSCC).Methods: A...Objective: Patients with head and neck cancer often suffer from malnutrition. This study aims to investigate the influence of body mass index(BMI) on the prognosis of laryngeal squamous cell carcinoma(LSCC).Methods: A total of 473 patients with LSCC initially treated at Sun Yat-sen University Cancer Center between January 2005 and July 2009 were retrospectively reviewed. Survival analysis was performed by the Kaplan-Meier method and Cox regression model.Results: Low BMI before treatment was significantly associated with poor overall survival in patients with LSCC(P<0.001). BMI was an independent prognostic factor for patients with LSCC.Conclusion: Leanness before treatment was associated with poor prognosis in patients with LSCC. Good nutritional status is favorable to improve survival in patients with LSCC.展开更多
Elevated levels of high mobility group protein B1(HMGB1)play a significant role in the pathogenesis of many diseases,but is particularly important for the formation of malignant tumors.Nonetheless,the function of HMGB...Elevated levels of high mobility group protein B1(HMGB1)play a significant role in the pathogenesis of many diseases,but is particularly important for the formation of malignant tumors.Nonetheless,the function of HMGB1 and the underlying mechanism of laryngeal squamous cell carcinoma(LSCC)remain incompletely understood,causing uncertainty.Here we found immunohistochemistry from 97 LSCC tissues showed HMGB1 was upreg-ulated,which was associated with poor differentiation.HMGB1 knockdown could significantly inhibit wound closure and colony formation.The full-genome gene expression microarray was performed to investigate the mechanism.After knockdown of HMGB1 by siRNA,among the expressed differential genes,10 genes were ran-domly selected for validation.Then,shRNA lentivirus targeting these genes were constructed to explore their role in LSCC by cell proliferation assay.LSM6 downregulation was dramatically promoted by HMGB1 knockdown,resulting in higher expression in LSCC tissues.Furthermore,downregulation of LSM6 could significantly suppress cell proliferation,migration and colony formation.This study indicated that HMGB1 promoted LSCC cell malig-nant phenotypes through regulation of LSM6.We anticipate that HMGB1-LSM6 could be a putative therapeutic target for LSCC.展开更多
Objective: To study the prognostic value of the pathological margin and molecular margin marked by eIF4E and P53 protein in laryngeal carcinoma. Methods: The prognostic value of pathological and molecular margin was s...Objective: To study the prognostic value of the pathological margin and molecular margin marked by eIF4E and P53 protein in laryngeal carcinoma. Methods: The prognostic value of pathological and molecular margin was studied in 253 cases and 67 cases respectively, the latter were pathological negative margin chosen from the former. Immunohistochemisty was used to detect the expression of eIF4E and p53 proteins. Results: The rate of pathological, p53 and eIF4E positive margins was 20.2%, 19.4% and 32.8% respectively. The recurrent rate of those with positive margins was higher than that of negative margins, which including pathological margin (70.6% vs 35.1%, P =0.0000), p53 margin (69.2% vs 33.3%, P =0.018) and eIF4E margin (63.6% vs 28.9%, P =0.018); The survival rate of those with negative margins was higher than those with positive margins, including pathological margin (the 5-year cumulative survival rate was 37.52% and 64.37% respectively, P =0.0023), p53 margin (the 5-year cumulative survival rate was 24.62% and 75.69% respectively, P =0.0012) and eIF4E margin (the 5-year cumulative survival rate was 43.31% and 77.52% respectively, P =0.0006). Conclusion: The prognosis of those with both pathological and molecular positive margins was worse than that of the negative margins; Both the eIF4E and p53 were useful markers to pick out the poor prognostic patients from those with pathological negative margin, and the former seemed to be more potential.展开更多
Objective: To investigate the expression of K-ras in human laryngeal squamous cell carcinoma cell lines (Hep-2) and its significance for establishing a solid foundation for further study of the relationship between...Objective: To investigate the expression of K-ras in human laryngeal squamous cell carcinoma cell lines (Hep-2) and its significance for establishing a solid foundation for further study of the relationship between human laryngeal squamous cell carcinoma and K-ras gene point mutations. Methods: The expression of K-ras in human laryngeal squamous cell carcinoma cell lines (Hep-2) and human pancreatic carcinoma cell lines (MIAPaCa-2) was detected by using RT-PCR. Results: The expression of K-ras mRNA in Hep-2 and MIAPaCa-2 was strong and positive. Conclusion: The expression of K-ras mRNA in human laryngeal squamous cell carcinoma cell lines (Hep-2) is positive. Development of laryngeal carcinoma might be related to the activation of K-ras gene point mutation.展开更多
Objective: To discuss the effect and mechanism of miR-34 a on the proliferation, apoptosis and invasion of laryngeal carcinoma cells. Methods: The laryngeal squamous carcinoma Hep2 cells were transiently transfected w...Objective: To discuss the effect and mechanism of miR-34 a on the proliferation, apoptosis and invasion of laryngeal carcinoma cells. Methods: The laryngeal squamous carcinoma Hep2 cells were transiently transfected with miR-34 a mimics and miR-34 a NC. The MTT, colony-forming assay, Hoechst staining and Annexin V-PI double staining flow cytometry were employed to detect the effect of miR-34 a on the viability and apoptosis of laryngeal squamous carcinoma Hep2 cells; Transwell assay to defect the effect of miR-34 a on the migration and invasion of laryngeal squamous carcinoma Hep2 cells; western blot and RTPCR assay to defect the effect of miR-34 a mimics on the expression of survivin and Ki-67 m RNA in laryngeal squamous carcinoma Hep2 cells. Results: Compared with miR-34 a NC group, the cell viability in miR-34 mimics group was significantly decreased(P<0.01), the cell apoptosis rate was significantly increased(P<0.01), the abilities of cell migration and invasion were significantly reduced(P<0.01) and the expression of survivin and Ki-67 m RNA was significantly decreased(P<0.01). Conclusions: The increased expression of miR-34 a can induce the apoptosis of Hep2 laryngeal carcinoma cells and inhibit the cell proliferation and invasion, which is related to the down-regulated expression of survivin and Ki-67.展开更多
Objective: To investigate PIK3CA mutation in Chinese patients with lung squamous cell carcinoma (LSCC) and explore their relationship with clinicopathological profiles. Methods: Tumor samples from 123 cases of LSC...Objective: To investigate PIK3CA mutation in Chinese patients with lung squamous cell carcinoma (LSCC) and explore their relationship with clinicopathological profiles. Methods: Tumor samples from 123 cases of LSCC were included in this study. PIK3CA mutations in exon 9 and 20 were screened by pyrosequencing and confirmed by clone sequencing or amplification refractory mutation system (ARMS). Denaturing performance liquid chromatography (DHPLC) was employed for evaluation of EGFR mutation in exon 19, 21 and KRAS mutation. Results: PIK3CA mutations were found in 3 (2.4%) patients. The mutation type included E545K, E452Q and H1047R. Of these three patients, one coupled with EGFR mutation, and the other two coupled with PIK3CA amplification. All the three patients shared the same clinicopathologic characteristics: male, less than 60 years old, had smoke history, stage III and carried wild-type KRAS. Conclusions: The frequency of PIK3CA mutation is low in Chinese patients with LSCC. The mutational status of PIK3CA is not mutually exclusive to EGFR mutation.展开更多
The studies described herein emphasize HPVDNA detection by applying consensus primers and multiple primers of modified polymerase chain reaction (PCR) to 124 cases of fresh tissue samples with different lesions of lar...The studies described herein emphasize HPVDNA detection by applying consensus primers and multiple primers of modified polymerase chain reaction (PCR) to 124 cases of fresh tissue samples with different lesions of larynx. The consensus primers used were able to detect 9 types of HPVsDNAs ( HPV 6 , 11 , 16 , 18, 31 , 33,35, 42, and 583 , from which the positive cases were picked out for further identification of their genometypes of HPV-DNA by using multiple primers PCR. The results areas follows : (1)In the group of laryngeal carcinoma,the total positive rate of HPV infection was 49. 1 %(28/57) : 15. 8%(9/57)for HPV18, 12. 3%(7/57)for HPV16,5. 3 %(3/57) dual infection for HPV16 and HPV18 , 3. 5%(2/57) for mixed infection of HPV6/11 and HPV18 , and 12. 3%(7/57)for the other types. (2) In the cervical metastatic lymphnode group, 3 of the 14 cases (21. 4%) of cervical metastatic lymphnode showed positive HPV, among which there was 1 case of HPV16 infection , 1 case of HPV18 infection ,and 1 case of HPV16 and HPV18 dual infection, resulting in a rate at 7. 1% for the respective cases immediately above. (3) In the pecarcinomatous lesion group ,the positive rate of HPV infection tmixed infection of HPV6/11 and HPV18) was 11. 1 %(1/9). (4)In the vocal cord polypus group , the rate of positive reaction (HPV6/11) was 7.1% (1/14). (5) In the nomal laryngeal tissue group , 15 cases of normal laryngeal tissue adjacent to the carcinoma and 15 cases of normal laryngeal tissue opposite to the carcinoma were HPV-DNA negative.The results showed that the occurrence and development of laryngeal carcinoma were closely related to HPV infection. The distribution of genometypes of HPV varied in different lesions of larynx. The carcinogenic action of HPV in laryngeal carcinoma is also discussed in this paper.展开更多
Tumor-associated macrophages(TAMs) can elicit contrasting effects on tumor progression,depending on different tumor microenvironment.This study aimed to explore the correlation between TAM infiltration and clinicopath...Tumor-associated macrophages(TAMs) can elicit contrasting effects on tumor progression,depending on different tumor microenvironment.This study aimed to explore the correlation between TAM infiltration and clinicopathologic characteristics,metastasis,and prognosis of supraglottic laryngeal carcinoma.TAMs in intratumoral and peritumoral regions of 84 specimens of supraglottic laryngeal carcinoma tissues were detected by immunohistochemical staining with monoclonal CD68 antibody.The density of peritumoral CD68+ TAMs in recurrence cases(9/11) and in dead cases(17/23) were significantly higher than those in non-recurrence cases(33/73) and in survival cases(25/61),with significant differences(P = 0.024 and 0.007,respectively).The Kaplan-Meier survival analysis showed a significant relationship between the infiltration of both intratumoral and peritumoral CD68 + TAMs and the overall survival of patients.The 5year survival rate was significantly lower in the group with a high density of intratumoral CD68+ TAMs than in the group with a low density(39.6% vs.82.5%,P < 0.05).Similarly,the 5-year survival rate was significantly lower in the group with a high density of peritumoral CD68+ TAMs than in the group with a low density(50.6% vs.73.1%,P < 0.05).Cox regression analysis revealed that T classification,distant metastasis,and intratumoral or peritumoral CD68 + TAMs were independent factors for disease-free survival,whereas T classification and intratumoral CD68 + TAMs were independent factors for overall survival.The results indicate that TAM infiltration in supraglottic laryngeal carcinoma can be used to predict metastasis and prognosis and is an independent factor for prognosis.展开更多
基金supported by a grant Hebei Provincial Health Commission project from the Foundation of Basic Research(No.20191843).
文摘Objective:Through integrated bioinformatics analysis,the goal of this work was to find new,characterised N7-methylguanosine modification-related long non-coding RNAs(m7G-lncRNAs)that might be used to predict the prognosis of laryngeal squamous cell carcinoma(LSCC).Methods:The clinical data and LSCC gene expression data for the current investigation were initially retrieved from the TCGA database&sanitised.Then,using co-expression analysis of m7G-associated mRNAs&lncRNAs&differential expression analysis(DEA)among LSCC&normal sample categories,we discovered lncRNAs that were connected to m7G.The prognosis prediction model was built for the training category using univariate&multivariate COX regression&LASSO regression analyses,&the model’s efficacy was checked against the test category data.In addition,we conducted DEA of prognostic m7G-lncRNAs among LSCC&normal sample categories&compiled a list of co-expression networks&the structure of prognosis m7G-lncRNAs.To compare the prognoses for individuals with LSCC in the high-&low-risk categories in the prognosis prediction model,survival and risk assessments were also carried out.Finally,we created a nomogram to accurately forecast the outcomes of LSCC patients&created receiver operating characteristic(ROC)curves to assess the prognosis prediction model’s predictive capability.Results:Using co-expression network analysis&differential expression analysis,we discovered 774 m7G-lncRNAs and 551 DEm7G-lncRNAs,respectively.We then constructed a prognosis prediction model for six m7G-lncRNAs(FLG−AS1,RHOA−IT1,AC020913.3,AC027307.2,AC010973.2 and AC010789.1),identified 32 DEPm7G-lncRNAs,analyzed the correlation between 32 DEPm7G-lncRNAs and 13 DEPm7G-mRNAs,and performed survival analyses and risk analyses of the prognosis prediction model to assess the prognostic performance of LSCC patients.By displaying ROC curves and a nomogram,we finally checked the prognosis prediction model's accuracy.Conclusion:By creating novel predictive lncRNA signatures for clinical diagnosis&therapy,our findings will contribute to understanding the pathogenetic process of LSCC.
文摘Summary: To investigate the expression of hypoxia inducible factor-1 alpha (HIF-1α) and its relationship to apoptosis and proliferation in laryngeal squamous cell carcinoma (LSCC), immunohistochemical method was used to detect the expression of HIF-1α and PCNA. Tunnel technique was used to detect in situ cell apoptosis in LSCC. Our results showed that the expression of HIF-1α was related to the clinical stages of cancer and lymph node metastasis (P<0.05). The relationship between HIF-1α and PCNA was statistically significant (P<0.05) and no relationship was found between HIF-1α and apoptosis (P>0.05) It is concluded that HIF-1α plays a role in the carcinogenesis of laryngeal carcinoma and is correlated with proliferation, but bears no relationship with the apoptosis of tumor cells in LSCC.
文摘n order to study the expressions of vascular endothelial growth factor (VEGF) and cyclooxygenase-2 (COX-2) in human laryngeal squamous cell carcinoma (LSCC) and its significance, the expression of VEGF mRNA and COX-2 mRNA in 62 cases of LSCC and 54 adjacent noncancerous laryngeal tissues and 9 normal human laryngeal mucous tissues was detected by using techniques of semi-quantitative RT-PCR. It was found that the expression level of VEGF and COX-2 mRNA was significantly increased in LSCC as compared with that in the normal human laryngeal mucous tissues (both P〈0. 01), and the expression level of VEGF and COX-2 mRNA were significantly increased in stage Ⅲ+ Ⅳtissues of LSCC as compared with the stage Ⅰ + Ⅱ tissues of LSCC (P 〈0.01). There was a high positive correlation between VEGF and COX-2 expression in LSCC (r= 0. 756,P〈0.01). These data raise the possibility that VEGF and COX-2 may play key roles in the growth, invasion and metastasis of LSCC.
文摘Objective:To evaluate the short-term effects of neoadjuvant chemotherapy with pingyangmycin(PYM)in the treat-ment of laryngeal squamous cell carcinoma.Methods:24 cases of laryngeal squamous cell carcinoma were treated with PYM before the operation,and the surgeries were undergone within one week after neoadjuvant chemotherapy.PCNA,p53,Bcl-2 and CD44v6 were detected in the specimens of tumor,retreated tumor and normal tissue using immunohistochemical methods.Results:Apoptosis could be detected more often in specimens with tumor and retreated tumor after chemotherapy than that before.The expression of PCNA,p53,Bcl-2 and CD44v6 in tumor tissue after neoadjuvant chemotherapy with PYM was weaker than that before the chemotherapy.There was significant difference in the positive ratio of PCNA,p53,Bcl-2 and CD44v6 be-tween retreated tumor and tumor.Conclusion:After neoadjuvant chemotherapy with PYM,a large number of tumor cells died.The amplification and metastasis of tumor were suppressed by neoadjuvant chemotherapy with PYM.
基金This work was supported by the National Brilliant Youth Science Foundation of China(No. 39925035) Ministry of Education Colleges and Universities Core Teachers Foundation of China (2000), College and University Doctoral Studies Special Purpose Scientific Research Foundation of China(2002).
文摘OBJECTIVE To investigate the prognostic value of measuring Ki67 and VEGF expression in laryngeal squamous cell carcinoma (LSCC). METHODS The expression of Ki67 and VEGF in 32 LSCC tissues was studied by immunohistochemical staining. Of these cases, 5 recurred (recurrent group), 3 cases metastasized (metastatic group), 8 cases died (deceased group) and 24 cased survived (survival group) over a 3 year period of follow-up after their operation. RESULTS The expression of Ki67 and VEGF in the deceased group was higher compared to that in the survival group (P<0.01). Overexpression of Ki67 was found in the recurrent group and in the metastatic group (P< 0.05). VEGF expression was higher in the recurrent group than in the non recurrent group (P<0.05). With Cox-regression of multivariate analysis, Ki67 (RR:3.236; P=0.001), the clinical T stage (RR: 1.382; P=0.029) and metastasis in lymph nodes (RR:0.316; P=0.033) were shown to be independent prognostic factors for survival of LSCC patients. CONCLUSION Ki67 and VEGF expression is related to the prognosis of LSCC. Overexpression of the 2 markers indicated poor prognosis of the disease, a finding which might be helpful for the treatment of laryngocar-cinoma.
文摘Background: Despite recent advances in clinical management of laryngeal squamous cell carcinoma (LSCC), the overall 5-year survival continues to be poor. Consequently, biomarkers of treatment response will need to be identified. Proteomic strategies are one way to attempt to identify such biomarkers. Methods: The Medline, Embase and Cochrane Library databases were systematically searched until 1st March 2014 using the terms “larynx”, “squamous cell carcinoma”, “proteomic”, and “biomarker”. Articles which met inclusion criteria were assessed for the type of biomarker investigated, the proteomic technique used, and whether any validation had been performed. Results: Six studies identified biomarkers, including UCRP, ceramides, uPA, MT1-MMP, stratifin, transferrin, albumin, S100 calcium-binding protein A9, stathmin, enolase, PLAU, IGFBP7, MMP14, THBS1, and transthyretin. Transferrin was the only biomarker to appear in more than one study. Conclusions: Our review identified several potential biomarkers of outcome in LSCC. Well designed studies will need to further validate their use in the future.
基金J. Chad Brenner received funding from NIH (Grants No. U01DE025184 and P30: CA046592 S1)Andrew C. Birkeland and Rebecca Hoesli received support from University of Michigan Otolaryngology Resident Research (Grant No. T32DC005356)Megan L. Ludwig was supported by NIH (Grant No. T-32-GM007315)
文摘Laryngeal squamous cell carcinoma(LSCC) remains a highly morbid and fatal disease. Historically, it has been a model example for organ preservation and treatment stratification paradigms. Unfortunately, survival for LSCC has stagnated over the past few decades. As the era of next-generation sequencing and personalized treatment for cancer approaches, LSCC may be an ideal disease for consideration of further treatment stratification and personalization. Here, we will discuss the important history of LSCC as a model system for organ preservation, unique and potentially targetable genetic signatures of LSCC, and methods for bringing stratified, personalized treatment strategies to the 21^(st) century.
基金The project supported by National Natural Science Foundation of China(31271444,81201726)the Guangdong Natural Science Funds(2015TQ01R350,2014A030313057)the Guangdong Science and Technology Program(2016A050502027,2013B021800088)
文摘OBJECTIVE To investigate the clinical and functional association of mi R-194 in human laryngeal squamous cell carcinoma(LSCC).METHODS Cell growth was measured by MTT assay.Cel cycle distribution was detected using PI staining by flow cytometric analysis.Cell migration and invasion were examined by wound healing assay and transwell assay.The 3′-UTR activity was detected by luciferase assay.The expression level of proteins and mR NA were analysed by Western blotting,immunohistochemistry and q RT-PCR.Mouse xenograft model was established to observe the tumor growth in vivo.RESULTS The expression level of miR-194 is significantly lower in clinical LSCC tissues compared with normal tissues,and is correlated with lymph node metastasis and TNM stage.Kaplan-Meier analysis shows that high miR-194 expression predicts a favorable outcome for LSCC patients.Functional assays show that enforced expression of mi R-194 inhibits the growth,migration,invasion and drug-resistance of LSCC cells.Moreover,Wee1 is identified as a novel functional target of mi R-194.Exogenous expression of Wee1 protein in mi R-194-over expressing cells partially reverses the suppressive effects of mi R-194 on LSCC cells.In addition,Wee1 was abnormally overexpressed in clinical LSCC tissues,and its protein levels were inversely correlated with miR-194 expression.High Wee1 protein level was also associated with TNM stage,lymph node metastasis and poor prognosis.CONCLUSION Our study provides new sights into the role of miR-194/Wee1 axis in LSCC,and suggests a novel miR-194/Wee1-based clinical intervention target for LSCC patients.
文摘Objective:Laryngeal squamous cell carcinoma(LSCC) is a common malignant tumor in Northeast China and is frequently associated with well-established risk factors like smoking and alcohol abuse.Human papilloma virus(HPV) is an epitheliotropic oncogenic virus that has been detected in a variety of head and neck tumors including LSCC.This retrospective study was to investigate the prevalence of HPV infection in patients with LSCC.Methods:In situ hybridization was performed in 99 patients with LSCC to detect the expression of HPV-16 E6 mRNA.Results:The positive rate of HPV16 E6 mRNA was 36.36%(36/99) in laryngeal squamous cell carcinoma(LSCC),whereas only 3 of 50(6%) specimens of the normal laryngeal mucosa as a control group showed positive results(P0.05).Additionally,there was no corelation between HPV16 and age,gender,clinical stage,nodal status and tumor site(P0.05).Conclusion:The results suggest that the increased prevalence of HPV infection compared to normal laryngeal mucosa and the fact that high-risk HPV types(especially type 16) were the most frequently identified do not allow the exclusion of HPV as a risk factor in laryngeal squamous cell carcinoma.However,their clinical value remains to be further investigated.
基金This work was supported by a grant from the National Brilliant Youth Science Foundation of China (No. 39925035) The Colleges and Universities Backbone Teachers’ Foundation of Ministry of Education of China (2000) The Colleges and Universities Doctor Subject Point Special Purpose Scientific Research Foundation of China (2002).
文摘Objective: To study the correlation between Ki67 and vascular endothelial growth factor(VEGF) and the significance of their expression in laryngeal squamous cell carcinoma(LSCC). Methods: The expressions of Ki67 and VEGF in 40 cases of LSCC and 5 cases of normal laryngeal mucosa were examined by immunohistochemical staining. Results: The expression levels of Ki67 and VEGF in LSCC tissue were higher than in normal laryngeal mucosa (Ki67: P〈0.001, VEGF: P〈0.001). The two indexes' levels in patients of different age or different sex had no significant difference (P〉0.05). They were higher in LSCC with metastasis of lymph nodes than in patients without metastasis (Ki67: P=0.034, VEGF: P=0.006). The expressions of the two genes elevated correspondingly along with the development of LSCC T stage (P〈0.05). In addition, correlation analysis indicated that the expression of Ki67 had a positive correlation with VEGF in LSCC(r=0.823, P〈0.01). Conclusion: Ki67 and VEGF are objective indexes for the biological behavior of LSCC, and they might be helpful to the diagnosis, treatment and prognosis of laryngocarcinoma.
基金supported by the Science and Technology Planning Project of Guangdong Province, China (Grant No. 2010B031600237)
文摘Objective: Patients with head and neck cancer often suffer from malnutrition. This study aims to investigate the influence of body mass index(BMI) on the prognosis of laryngeal squamous cell carcinoma(LSCC).Methods: A total of 473 patients with LSCC initially treated at Sun Yat-sen University Cancer Center between January 2005 and July 2009 were retrospectively reviewed. Survival analysis was performed by the Kaplan-Meier method and Cox regression model.Results: Low BMI before treatment was significantly associated with poor overall survival in patients with LSCC(P<0.001). BMI was an independent prognostic factor for patients with LSCC.Conclusion: Leanness before treatment was associated with poor prognosis in patients with LSCC. Good nutritional status is favorable to improve survival in patients with LSCC.
基金The funding for this study was provided by the National Natural Science Foundation of China(grant numbers 82371156 and 82171145)the Jiangsu Provincial Medical Key Discipline Laboratory(grant number ZDXK202243).
文摘Elevated levels of high mobility group protein B1(HMGB1)play a significant role in the pathogenesis of many diseases,but is particularly important for the formation of malignant tumors.Nonetheless,the function of HMGB1 and the underlying mechanism of laryngeal squamous cell carcinoma(LSCC)remain incompletely understood,causing uncertainty.Here we found immunohistochemistry from 97 LSCC tissues showed HMGB1 was upreg-ulated,which was associated with poor differentiation.HMGB1 knockdown could significantly inhibit wound closure and colony formation.The full-genome gene expression microarray was performed to investigate the mechanism.After knockdown of HMGB1 by siRNA,among the expressed differential genes,10 genes were ran-domly selected for validation.Then,shRNA lentivirus targeting these genes were constructed to explore their role in LSCC by cell proliferation assay.LSM6 downregulation was dramatically promoted by HMGB1 knockdown,resulting in higher expression in LSCC tissues.Furthermore,downregulation of LSM6 could significantly suppress cell proliferation,migration and colony formation.This study indicated that HMGB1 promoted LSCC cell malig-nant phenotypes through regulation of LSM6.We anticipate that HMGB1-LSM6 could be a putative therapeutic target for LSCC.
文摘Objective: To study the prognostic value of the pathological margin and molecular margin marked by eIF4E and P53 protein in laryngeal carcinoma. Methods: The prognostic value of pathological and molecular margin was studied in 253 cases and 67 cases respectively, the latter were pathological negative margin chosen from the former. Immunohistochemisty was used to detect the expression of eIF4E and p53 proteins. Results: The rate of pathological, p53 and eIF4E positive margins was 20.2%, 19.4% and 32.8% respectively. The recurrent rate of those with positive margins was higher than that of negative margins, which including pathological margin (70.6% vs 35.1%, P =0.0000), p53 margin (69.2% vs 33.3%, P =0.018) and eIF4E margin (63.6% vs 28.9%, P =0.018); The survival rate of those with negative margins was higher than those with positive margins, including pathological margin (the 5-year cumulative survival rate was 37.52% and 64.37% respectively, P =0.0023), p53 margin (the 5-year cumulative survival rate was 24.62% and 75.69% respectively, P =0.0012) and eIF4E margin (the 5-year cumulative survival rate was 43.31% and 77.52% respectively, P =0.0006). Conclusion: The prognosis of those with both pathological and molecular positive margins was worse than that of the negative margins; Both the eIF4E and p53 were useful markers to pick out the poor prognostic patients from those with pathological negative margin, and the former seemed to be more potential.
基金This work was supported by a grant from the National Natural Science Foundation of China(No. 30070809).
文摘Objective: To investigate the expression of K-ras in human laryngeal squamous cell carcinoma cell lines (Hep-2) and its significance for establishing a solid foundation for further study of the relationship between human laryngeal squamous cell carcinoma and K-ras gene point mutations. Methods: The expression of K-ras in human laryngeal squamous cell carcinoma cell lines (Hep-2) and human pancreatic carcinoma cell lines (MIAPaCa-2) was detected by using RT-PCR. Results: The expression of K-ras mRNA in Hep-2 and MIAPaCa-2 was strong and positive. Conclusion: The expression of K-ras mRNA in human laryngeal squamous cell carcinoma cell lines (Hep-2) is positive. Development of laryngeal carcinoma might be related to the activation of K-ras gene point mutation.
基金supported by Handan Science and Technology Bureau(Project No.1323108088)
文摘Objective: To discuss the effect and mechanism of miR-34 a on the proliferation, apoptosis and invasion of laryngeal carcinoma cells. Methods: The laryngeal squamous carcinoma Hep2 cells were transiently transfected with miR-34 a mimics and miR-34 a NC. The MTT, colony-forming assay, Hoechst staining and Annexin V-PI double staining flow cytometry were employed to detect the effect of miR-34 a on the viability and apoptosis of laryngeal squamous carcinoma Hep2 cells; Transwell assay to defect the effect of miR-34 a on the migration and invasion of laryngeal squamous carcinoma Hep2 cells; western blot and RTPCR assay to defect the effect of miR-34 a mimics on the expression of survivin and Ki-67 m RNA in laryngeal squamous carcinoma Hep2 cells. Results: Compared with miR-34 a NC group, the cell viability in miR-34 mimics group was significantly decreased(P<0.01), the cell apoptosis rate was significantly increased(P<0.01), the abilities of cell migration and invasion were significantly reduced(P<0.01) and the expression of survivin and Ki-67 m RNA was significantly decreased(P<0.01). Conclusions: The increased expression of miR-34 a can induce the apoptosis of Hep2 laryngeal carcinoma cells and inhibit the cell proliferation and invasion, which is related to the down-regulated expression of survivin and Ki-67.
基金supported by grants from National Natural Sciences Foundation Distinguished Young Scholars(81025012)National Natural Sciences Foundation General Program (81172235)+2 种基金the Capital Development Foundation(2007-1023)Beijing Health Systems Academic Leader(2011-2-22)Science and Technology Project of Beijing(Z090507017709015)
文摘Objective: To investigate PIK3CA mutation in Chinese patients with lung squamous cell carcinoma (LSCC) and explore their relationship with clinicopathological profiles. Methods: Tumor samples from 123 cases of LSCC were included in this study. PIK3CA mutations in exon 9 and 20 were screened by pyrosequencing and confirmed by clone sequencing or amplification refractory mutation system (ARMS). Denaturing performance liquid chromatography (DHPLC) was employed for evaluation of EGFR mutation in exon 19, 21 and KRAS mutation. Results: PIK3CA mutations were found in 3 (2.4%) patients. The mutation type included E545K, E452Q and H1047R. Of these three patients, one coupled with EGFR mutation, and the other two coupled with PIK3CA amplification. All the three patients shared the same clinicopathologic characteristics: male, less than 60 years old, had smoke history, stage III and carried wild-type KRAS. Conclusions: The frequency of PIK3CA mutation is low in Chinese patients with LSCC. The mutational status of PIK3CA is not mutually exclusive to EGFR mutation.
文摘The studies described herein emphasize HPVDNA detection by applying consensus primers and multiple primers of modified polymerase chain reaction (PCR) to 124 cases of fresh tissue samples with different lesions of larynx. The consensus primers used were able to detect 9 types of HPVsDNAs ( HPV 6 , 11 , 16 , 18, 31 , 33,35, 42, and 583 , from which the positive cases were picked out for further identification of their genometypes of HPV-DNA by using multiple primers PCR. The results areas follows : (1)In the group of laryngeal carcinoma,the total positive rate of HPV infection was 49. 1 %(28/57) : 15. 8%(9/57)for HPV18, 12. 3%(7/57)for HPV16,5. 3 %(3/57) dual infection for HPV16 and HPV18 , 3. 5%(2/57) for mixed infection of HPV6/11 and HPV18 , and 12. 3%(7/57)for the other types. (2) In the cervical metastatic lymphnode group, 3 of the 14 cases (21. 4%) of cervical metastatic lymphnode showed positive HPV, among which there was 1 case of HPV16 infection , 1 case of HPV18 infection ,and 1 case of HPV16 and HPV18 dual infection, resulting in a rate at 7. 1% for the respective cases immediately above. (3) In the pecarcinomatous lesion group ,the positive rate of HPV infection tmixed infection of HPV6/11 and HPV18) was 11. 1 %(1/9). (4)In the vocal cord polypus group , the rate of positive reaction (HPV6/11) was 7.1% (1/14). (5) In the nomal laryngeal tissue group , 15 cases of normal laryngeal tissue adjacent to the carcinoma and 15 cases of normal laryngeal tissue opposite to the carcinoma were HPV-DNA negative.The results showed that the occurrence and development of laryngeal carcinoma were closely related to HPV infection. The distribution of genometypes of HPV varied in different lesions of larynx. The carcinogenic action of HPV in laryngeal carcinoma is also discussed in this paper.
基金supported by grant from Pujiang Talent Project of the Shanghai Science and Technology Committee (No. 07pj14064)
文摘Tumor-associated macrophages(TAMs) can elicit contrasting effects on tumor progression,depending on different tumor microenvironment.This study aimed to explore the correlation between TAM infiltration and clinicopathologic characteristics,metastasis,and prognosis of supraglottic laryngeal carcinoma.TAMs in intratumoral and peritumoral regions of 84 specimens of supraglottic laryngeal carcinoma tissues were detected by immunohistochemical staining with monoclonal CD68 antibody.The density of peritumoral CD68+ TAMs in recurrence cases(9/11) and in dead cases(17/23) were significantly higher than those in non-recurrence cases(33/73) and in survival cases(25/61),with significant differences(P = 0.024 and 0.007,respectively).The Kaplan-Meier survival analysis showed a significant relationship between the infiltration of both intratumoral and peritumoral CD68 + TAMs and the overall survival of patients.The 5year survival rate was significantly lower in the group with a high density of intratumoral CD68+ TAMs than in the group with a low density(39.6% vs.82.5%,P < 0.05).Similarly,the 5-year survival rate was significantly lower in the group with a high density of peritumoral CD68+ TAMs than in the group with a low density(50.6% vs.73.1%,P < 0.05).Cox regression analysis revealed that T classification,distant metastasis,and intratumoral or peritumoral CD68 + TAMs were independent factors for disease-free survival,whereas T classification and intratumoral CD68 + TAMs were independent factors for overall survival.The results indicate that TAM infiltration in supraglottic laryngeal carcinoma can be used to predict metastasis and prognosis and is an independent factor for prognosis.