RESUMO
Objective:To detect the differences in types and levels of amino acids in the peripheral serum of patients with laryngeal squamous cell carcinoma and non-tumor patients, and explore their relationship with clinical parameters of laryngeal squamous cell carcinoma as well as their clinical value in diagnosis. Methods:High-performance liquid chromatography-tandem mass spectrometryï¼HPLC-MSï¼ was employed to detect the serum amino acid contents and levels of 62 patients diagnosed with laryngeal carcinoma and 141 non-tumor patients at the First Affiliated Hospital of Jinzhou Medical University between September 2018 and February 2021. The study compared the differences in 22 non-essential and essential amino acids found in the serum between the experimental group and the control group. An ROC curve and risk scoring formula of multivariate linear logic regression model was utilized to evaluate the efficiency of serum amino acids in the early diagnosis of laryngeal carcinoma. Results:There were significant differences in the contents of fourteen types of amino acids between the experimental and control groups, with thirteen amino acids showing higher levels in the experimental groupï¼P<0.05ï¼. Seven of these amino acids were essential, including phenylalanine, threonine, leucine, valine, histidine, tyrosine, and citrulline. The other six amino acids were non-essential, including arginine, asparagine, cysteine, glycine, ornithine, and proline. Interestingly, the content of homocysteine in the experimental group was lower than that in the control groupï¼P=0.024ï¼. Further analysis showed that patients with laryngeal squamous cell carcinoma in TNM stage â and â ¡ had higher serum methionine levels compared to those in stages â ¢ and â £ï¼P=0.026ï¼. In addition, the content of serum histidine was higher in patients with poorly differentiated squamous cell carcinoma compared to those with well-differentiated squamous cell carcinomaï¼P=0.041ï¼. The level of asparagine in the serum of patients with laryngeal squamous cell carcinoma older than 64 years old was lower than that in patients younger than 64 years oldï¼P=0.033ï¼. The level of tryptophan in the serum of patients with a smoking history was lower than that in patients without a smoking historyï¼P=0.033ï¼. The level of citrulline in the serum of patients with a history of alcohol consumption was higher than that in patients with no history of alcohol consumptionï¼P=0.003ï¼. ROC curve analysis showed that out of the 14 different amino acids between the experimental and control groups, citrulline and cysteine were relatively effective as independent factors in the diagnosis of laryngeal squamous cell carcinoma, with an AUC of 0.856 and 0.850, respectively. Arginine was the most sensitive factor in the diagnosis of laryngeal squamous cell carcinomaï¼AUC=0.855ï¼. However, citrulline alone had the highest specificityï¼0.830ï¼ in the diagnosis of laryngeal squamous cell carcinoma, and the combination of 12 amino acids significantly improved the diagnostic efficiency of laryngeal squamous cell carcinoma, with an AUC of 0.946, sensitivity of 0.887, and specificity of 0.894. A risk score formula for a multivariate logistic regression model was established based on the differential amino acid content in the serum. The risk score of laryngeal squamous cell carcinoma group was higher than that of the non-tumor groupï¼P<0.001ï¼. The AUC of risk score in the diagnosis of laryngeal squamous cell carcinoma was 0.953 with sensitivity and specificity of 0.957 and 0.855. Conclusion:This study found that there are differences in the contents of 14 amino acids among which 13 amino acids were increased in serum of patients with laryngeal squamous cell carcinoma, and were associated with age, clinical stage, pathological differentiation, smoking, and drinking. Combined detection of 12 amino acids can improve the diagnostic efficiency of laryngeal squamous cell carcinoma and serve as potential markers for the auxiliary diagnosis of laryngeal squamous cell carcinoma using peripheral blood samples. Additionally, the established risk score model was found to be more effective in the diagnosis of laryngeal squamous cell carcinoma, indicating its important potential value as an auxiliary diagnostic tool.
Assuntos
Aminoácidos , Carcinoma de Células Escamosas , Neoplasias Laríngeas , Humanos , Neoplasias Laríngeas/sangue , Neoplasias Laríngeas/diagnóstico , Masculino , Feminino , Pessoa de Meia-Idade , Aminoácidos/sangue , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/diagnóstico , Cromatografia Líquida de Alta Pressão , Espectrometria de Massas em Tandem , Curva ROC , Estudos de Casos e ControlesRESUMO
BACKGROUND: The growing understanding of cancer biology and the establishment of new treatment modalities has not yielded the expected results in terms of survival for Laryngeal Squamous Cell Cancer (LSCC). Early diagnosis, as well as prompt identification of patients with high risk of relapse would ensure greater chance of therapeutic success. However, this goal remains a challenge due to the absence of specific biomarkers for this neoplasm. METHODS: Serum samples from 45 LSCC patients and 23 healthy donors were collected for miRNA expression profiling by TaqMan Array analysis. Additional 20 patients and 42 healthy volunteers were included for the validation set, reaching an equal number of clinical samples for each group. The potential diagnostic ability of the such identified three-miRNA signature was confirmed by ROC analysis. Moreover, each miRNA was analyzed for the possible correlation with HNSCC patients' survival and TNM status by online databases Kaplan-Meier (KM) plotter and OncomiR. In silico analysis of common candidate targets and their network relevance to predict shared biological functions was finally performed by PANTHER and GeneMANIA software. RESULTS: We characterized serum miRNA profile of LSCC patients identifying a novel molecular signature, including miR-223, miR-93 and miR-532, as circulating marker endowed with high selectivity and specificity. The oncogenic effect and the prognostic significance of each miRNA was investigated by bioinformatic analysis, denoting significant correlation with OS. To analyse the molecular basis underlying the pro-tumorigenic role of the signature, we focused on the simultaneously regulated gene targets-IL6ST, GTDC1, MAP1B, CPEB3, PRKACB, NFIB, PURB, ATP2B1, ZNF148, PSD3, TBC1D15, PURA, KLF12-found by prediction tools and deepened for their functional role by pathway enrichment analysis. The results showed the involvement of 7 different biological processes, among which inflammation, proliferation, migration, apoptosis and angiogenesis. CONCLUSIONS: In conclusion, we have identified a possible miRNA signature for early LSCC diagnosis and we assumed that miR-93, miR-223 and miR-532 could orchestrate the regulation of multiple cancer-related processes. These findings encourage the possibility to deepen the molecular mechanisms underlying their oncogenic role, for the desirable development of novel therapeutic opportunities based on the use of short single-stranded oligonucleotides acting as non-coding RNA antagonists in cancer.
Assuntos
Carcinoma de Células Escamosas , Biologia Computacional , Detecção Precoce de Câncer , Regulação Neoplásica da Expressão Gênica , Neoplasias Laríngeas , MicroRNAs , Humanos , Neoplasias Laríngeas/sangue , Neoplasias Laríngeas/genética , Neoplasias Laríngeas/diagnóstico , MicroRNAs/sangue , MicroRNAs/genética , Masculino , Feminino , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/diagnóstico , Pessoa de Meia-Idade , Perfilação da Expressão Gênica , Curva ROC , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Estimativa de Kaplan-Meier , Estudos de Casos e Controles , Redes Reguladoras de Genes , IdosoRESUMO
BACKGROUND: Exosomes are nanosized vesicles released from all cells into surrounding biofluids, including cancer cells, and represent a very promising direction in terms of minimally invasive approaches to early disease detection. They carry tumor-specific biological contents such as DNA, RNA, proteins, lipids, and sugars, as well as surface molecules that are able to pinpoint the cellular source. By the above criteria, exosomes may be stratified according to the presence of tissue and disease-specific signatures and, due to their stability in such biofluids as plasma and serum, they represent an indispensable source of vital clinical insights from liquid biopsies, even at the earliest stages of cancer. Therefore, our work aimed to isolate and characterize LCa patients' derived exosomes from serum by Flow Cytometry in order to define a specific epitope signature exploitable for early diagnosis. METHODS: Circulating exosomes were collected from serum collected from 30 LCa patients and 20 healthy volunteers by the use of antibody affinity method exploiting CD63 specific surface marker. Membrane epitopes were then characterized by Flow cytometry multiplex analysis and compared between LCa Patients and Healthy donors. Clinical data were also matched to obtain statistical correlation. RESULTS: A distinct overexpression of CD1c, CD2, CD3, CD4, CD11c, CD14, CD20, CD44, CD56, CD105, CD146, and CD209 was identified in LCa patients compared to healthy controls, correlating positively with tumor presence. Conversely, CD24, CD31, and CD40, though not overexpressed in tumor samples, showed a significant correlation with nodal involvement in LCa patients (p < 0.01). CONCLUSION: This approach could allow us to set up a cost-effective and less invasive liquid biopsy protocol from a simple blood collection in order to early diagnose LCa and improve patients' outcomes and quality of life.
Assuntos
Detecção Precoce de Câncer , Exossomos , Neoplasias Laríngeas , Humanos , Exossomos/metabolismo , Detecção Precoce de Câncer/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Neoplasias Laríngeas/diagnóstico , Neoplasias Laríngeas/sangue , Neoplasias Laríngeas/patologia , Idoso , Estudos de Casos e Controles , Citometria de Fluxo , Epitopos/imunologia , Epitopos/sangue , Biomarcadores Tumorais/sangue , AdultoRESUMO
BACKGROUND: We aimed to investigate the postoperative prognosis in patients with early-stage laryngeal squamous cell carcinoma (LSCC) in association with the preoperative blood markers and clinicopathological characteristics and to develop nomograms for individual risk prediction. METHODS: The clinical data of 353 patients with confirmed early-stage LSCC between 2009 and 2018 were retrospectively retrieved from the First Affiliated Hospital with Nanjing Medical University. All patients were randomly divided into the training and testing groups in a 7:3 ratio. Univariate and multivariate analyses were performed, followed by the construction of nomograms to predict recurrence-free survival (RFS) and overall survival (OS). Finally, the nomograms were verified internally, and the predictive capability of the nomograms was evaluated and compared with that of tumour T staging. RESULTS: Univariate and multivariate analyses identified platelet counts (PLT), fibrinogen (FIB), and platelet to lymphocyte ratio (PLR) were independent factors for RFS, and FIB, systemic immune-inflammation index (SII), and haemoglobin (HGB) were independent prognostic factors for OS. The nomograms showed higher predictive C-indexes than T staging. Furthermore, decision curve analysis (DCA) revealed that the net benefit of the nomograms' calculation model was superior to that of T staging. CONCLUSIONS: We established and validated nomograms to predict postoperative 1-, 3- and 5-year RFS and OS in patients with early-stage LSCC based on significant blood markers and clinicopathological characteristics. These models might help clinicians make personalized treatment decisions.
Assuntos
Neoplasias Laríngeas , Nomogramas , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Neoplasias Laríngeas/cirurgia , Neoplasias Laríngeas/patologia , Neoplasias Laríngeas/sangue , Neoplasias Laríngeas/mortalidade , Estudos Retrospectivos , Prognóstico , Estadiamento de Neoplasias , Carcinoma de Células Escamosas de Cabeça e Pescoço/cirurgia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/sangue , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Idoso , Taxa de Sobrevida , Seguimentos , Adulto , Biomarcadores Tumorais/sangueRESUMO
OBJECTIVES: The systemic inflammatory response is strongly involved in the progression of malignant tumors, and it is useful for predicting survival time and determining therapeutic effects. The inflammatory biomarkers, neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR) are used to assess post-treatment survival and recurrence in various malignant tumors.(Walsh et al., 2005; Burt et al., 2011; Smith et al., 2009) 1,2,3 These indicators may be effective as predictive markers for head and neck malignancies. METHODS: The participants were 125 glottic laryngeal and supraglottic cancer cases who received primary treatment in our department from 2010 to 2016. The NLR, LMR, and PLR for each patient were calculated in addition to the association with overall survival (OS) rate, disease-specific survival (DSS) rate, and laryngeal preservation rate for tumor location, T and N classification, TNM stage classification, treatment, and smoking. We investigated whether inflammatory biomarkers are useful for predicting prognosis. RESULTS: The cutoff values for NLR, LMR, and PLR on the ROC curve were 1.88, 5.57, and 108, respectively. Multivariate analysis with LMR 5.57 as the cutoff value showed significant differences in OS, DSS, and laryngeal preservation. However, setting the cutoff values for NLR 1.88 and PLR 108 showed significant differences only in OS and laryngeal preservation. CONCLUSION: LMR may be a total survival predictor of laryngeal cancer, including OS, DSS, and laryngeal preservation.
Assuntos
Neoplasias Laríngeas , Neutrófilos , Humanos , Neoplasias Laríngeas/mortalidade , Neoplasias Laríngeas/sangue , Neoplasias Laríngeas/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Prognóstico , Idoso , Biomarcadores Tumorais/sangue , Adulto , Linfócitos , Taxa de Sobrevida , Inflamação/sangue , Idoso de 80 Anos ou mais , Valor Preditivo dos Testes , Estudos Retrospectivos , Monócitos , Estadiamento de Neoplasias , Contagem de Plaquetas , PlaquetasRESUMO
OBJECTIVE: Diagnostic role of autoantibodies (AAb) as serological biomarkers has not been specifically investigated in laryngeal cancer (LC) previously. The study investigates the presence of anti-LC AAbs and their potential as a biomarker for early diagnosis of LC, to improve patient outcome. METHOD: Anti-LC AAb levels were investigated in LC patients (n = 30) and healthy individuals (n = 30) by indirect enzyme-linked immunosorbent assay (ELISA). Patient AAb levels were analyzed with various clinical factors, primarily tumor stage. RESULTS: AAb levels were significantly higher in LC patients than in the control group (P = .019). The diagnostic performance of AAb-level testing for LC detection presented a sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of 70% each. The positive likelihood (LR+) and negative likelihood (LR-) ratios were 2.33 and 0.43, respectively. AAb levels were independent of cancer stage (P = .708), duration since first appearance of symptoms (P = .228), duration of medical attention (P = .231), and degree of risk-factor exposure (P = .478). CONCLUSION: Significant level of AAbs could be detected among LC patients with good diagnostic performance, irrespective of stage. Thus, anti-LC AAbs reflect potential to be utilized as predictive biomarkers in early diagnostics of LC.
Assuntos
Autoanticorpos , Biomarcadores Tumorais , Ensaio de Imunoadsorção Enzimática , Neoplasias Laríngeas , Humanos , Neoplasias Laríngeas/diagnóstico , Neoplasias Laríngeas/sangue , Neoplasias Laríngeas/imunologia , Autoanticorpos/sangue , Masculino , Pessoa de Meia-Idade , Feminino , Biomarcadores Tumorais/sangue , Idoso , Sensibilidade e Especificidade , AdultoRESUMO
ABSTRACT: Laryngeal cancer (LC) as one of common malignant tumors in the head and neck region accounted for 1% to 5% of new cancer cases and was ranked as the third otolaryngology cancer. However, some patients with LC were diagnosed at the advanced stage, which can cause delayed diagnosis and treatment. It is an urgent task to seek effective biomarkers for the early diagnosis of LC aimed at alleviating suffering.A combination of dried blood spot sampling and direct infusion mass spectrometry technology was applied to 39 patients with LC and 53 healthy individuals. Multiple algorithms towards 93 metabolites including amino acids and carnitine/acylcarnitines were run for selecting differential metabolites. Furthermore, leave-one-out cross-validation method was used to evaluate diagnostic performance of selected metabolite biomarkers.A biomarker panel consisting of arginine, proline, hexacosanoic carnitine, ornithine /citrulline, and 3-hydroxy-octadecenoylcarnitine exhibited potential to distinguish patients with LC from healthy individuals, with a sensitivity of 0.8974 and a specificity of 0.8302 in leave-one-out cross-validation model.The metabolomic analysis of LC patients is beneficial to screen disease-associated biomarkers and develop new diagnostic approaches.
Assuntos
Teste em Amostras de Sangue Seco , Neoplasias Laríngeas/diagnóstico , Metabolômica/métodos , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Carnitina/análogos & derivados , Feminino , Humanos , Neoplasias Laríngeas/sangue , Masculino , Espectrometria de Massas , Pessoa de Meia-IdadeRESUMO
Stress contributes to various aspects of malignancy and could influence survival in laryngeal cancer patients. Among antioxidant mechanisms, zinc and the antioxidant enzymes superoxide dismutase 2, catalase and glutathione peroxidase 1 play a major role. The aim of this study was a prospective evaluation of the survival of patients with laryngeal cancer in relation to serum levels of zinc in combination with functional genotype differences of three key antioxidant enzymes. The study group consisted of 300 patients treated surgically for laryngeal cancer. Serum zinc levels and common polymorphisms in SOD2, CAT and GPX1 were analyzed. The risk of death in patients with the lowest zinc levels was increased in comparison with patients with the highest levels. Polymorphisms of antioxidant genes by themselves were not correlated with survival, however, serum zinc level impact on survival was stronger for SOD2 TC/TT and CAT CC variants. GPX1 polymorphisms did not correlate with zinc levels regarding survival. In conclusion, serum zinc concentration appears to be an important prognostic factor for survival of patients diagnosed with laryngeal cancer. When higher zinc levels were correlated with polymorphisms in SOD2 and CAT a further increase in survival was observed.
Assuntos
Genótipo , Neoplasias Laríngeas , Estresse Oxidativo , Zinco/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Laríngeas/sangue , Neoplasias Laríngeas/genética , Neoplasias Laríngeas/mortalidade , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/sangue , Proteínas de Neoplasias/genética , Taxa de SobrevidaRESUMO
Actin-binding proteins (ABPs) and various signaling systems are involved in the process of squamous cell carcinoma of the larynx and hypopharynx (SCCLH) metastasis. The clinical significance of these proteins has not yet been determined. We analyzed the relationship between the mRNA levels of cofilin 1 (CFL1), profilin 1 (PFN1), adenylyl cyclase-associated protein 1 (CAP1), SNAI1 and RND3 and SCCLH metastasis. The serum levels of the above ABPs were estimated and the relationship between them and their mRNA expressions was analyzed. The expression levels of ABP mRNAs were measured by real-time RT-PCR in paired tissue samples taken from 54 patients with SCCLH (T1-4N0-1M0). Expression analysis was performed using the 2-ΔΔCT method. The levels of ABPs in the blood serum were measured by ELISA. Statistical analysis was carried out using the SPSS Statistica 20.0 software package. No significant difference in the mRNA gene expression in tumor tissue of patients with T1-3N0M0 SCCLH and patients with T2-4N1-2M0 SCCLH was found. High expression of RND3 mRNA was accompanied by an increase in mRNA expression of all studied ABPs. In the blood serum of T2-4N1-2M0 patients, the level of PFN1 was lower by 21% and the level of CAP1 was higher by 75% than those observed in T1-4N0M0 patients. The data obtained showed that RND3 is involved in the regulation of molecular cascades of SCCLH metastasis. PFN1 and CAP1 serum levels can be good classifiers of metastases in patients with SCCLH.
Assuntos
Neoplasias Hipofaríngeas/metabolismo , Neoplasias Laríngeas/metabolismo , Proteínas dos Microfilamentos/genética , Adulto , Idoso , Carcinoma de Células Escamosas/patologia , Proteínas de Ciclo Celular/análise , Proteínas de Ciclo Celular/sangue , Proteínas de Ciclo Celular/genética , Cofilina 1/análise , Cofilina 1/sangue , Cofilina 1/genética , Proteínas do Citoesqueleto/análise , Proteínas do Citoesqueleto/sangue , Proteínas do Citoesqueleto/genética , Citoesqueleto/metabolismo , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Neoplasias Hipofaríngeas/sangue , Neoplasias Hipofaríngeas/genética , Neoplasias Laríngeas/sangue , Masculino , Proteínas dos Microfilamentos/metabolismo , Pessoa de Meia-Idade , Profilinas/análise , Profilinas/sangue , Profilinas/genética , RNA Mensageiro/genética , Federação Russa , Soro/metabolismo , Transdução de Sinais/genética , Fatores de Transcrição da Família Snail/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Proteínas rho de Ligação ao GTP/genéticaRESUMO
BACKGROUND: Laryngeal squamous cell carcinoma (LSCC) brings a heavy blow to the patient's voice. Transfer RNA (tRNA) is a common RNA, the roles of tRNAs in LSCC are largely unknown. METHODS: The tRNA expression profile in LSCC tissues and adjacent normal tissues was measured by a tRNA qRT-PCR array. The expression level of tRNAIni CAT in LSCC tissues and plasmas was detected by qRT-PCR. The receiver operating characteristic (ROC) curve was established. tRNAIni CAT was upregulated by a lentivirus vector in the LSCC cell line. Moreover, tRNAIni CAT was upregulated in LSCC xenograft nude mouse model and the xenografts were used for pathological analysis and transmission electron microscope (TEM) observation. RESULTS: The top 10 upregulated tRNAs were tRNALys CTT -1, tRNALeu TAA , tRNAPhe GAA , tRNALeu CAG , tRNATyr ATA , tRNAMet CAT , tRNATyr GTA -1, tRNAThr CGT , tRNATyr GTA -2, tRNAAla AGC ; and the top 10 downregulated tRNAs were tRNAIni CAT , mt-tRNAGlu TTC , tRNAVal CAC -3, mt-tRNATrp TCA , mt-tRNATyr GTA , mt-tRNALys TTT , mt-tRNAThr TGT , mt-tRNAAsp GTC , mt-tRNAAsn GTT , mt-tRNAPro TGG . tRNAIni CAT was downregulated in LSCC tissues and plasma. The area under the ROC curve (AUC) in LSCC tissues and the plasma of patients with LSCC was 0.717 and 0.808, respectively. tRNAIni CAT inhibited LSCC cell proliferation and promoted apoptosis. The in vivo results showed that tRNAIni CAT inhibited the growth of the xenografts and promoted apoptosis. CONCLUSIONS: This is the first study to provide tRNA expression profiles for LSCC tissues. tRNAIni CAT may be used as a new biomarker for the early diagnosis of LSCC. tRNAIni CAT inhibits cell proliferation and promotes apoptosis in vitro and in vivo.
Assuntos
Apoptose/genética , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Neoplasias Laríngeas/genética , Neoplasias Laríngeas/patologia , RNA de Transferência/metabolismo , Animais , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/diagnóstico , Linhagem Celular Tumoral , Proliferação de Células/genética , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Proteínas de Fluorescência Verde/metabolismo , Humanos , Neoplasias Laríngeas/sangue , Neoplasias Laríngeas/diagnóstico , Camundongos Endogâmicos BALB C , Camundongos Nus , RNA de Transferência/sangue , RNA de Transferência/genética , Curva ROC , Regulação para Cima/genética , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
OBJECTIVES: To determine the serum hypoxia-inducible factor-1, -2 and -3 (HIF-1, -2 and -3) levels in patients with laryngeal neoplasm, and to investigate their role in differential diagnosis, prediction of tumour characteristic and extension, and prognosis and survival. STUDY DESIGN: Prospective, cohort study at a tertiary referral centre. SETTINGS: The study was conducted in a tertiary medical centre. PARTICIPANTS: Patients with benign, premalignant and malignant laryngeal neoplasms were included. Sixty-four patients with a laryngeal neoplasm were enrolled. MAIN OUTCOME MEASURES: Serum HIF-1, -2 and -3 levels were measured from blood samples that were drawn before treatment, using ELISA. RESULTS: A statistically significant difference between benign (HIF-1, -2, -3:4046,1 pg/mL; 2581,5 pg/mL; 1321,0 pg/mL), premalignant (HIF-1, -2, -3:3630,3 pg/mL; 3229,7 pg/mL; 2549,8 pg/mL) and malignant (HIF-1, -2, -3:3576,7 pg/mL; 2595,8 pg/mL; 1106,3 pg/mL) laryngeal neoplasms was not detected when serum HIF-1, -2 and -3 levels were compared. However, high serum HIF-2 level adversely affected survival and locoregional control and had more than 7-fold increase in hazard ratio. Moreover, serum HIF-2 was an independent prognostic factor for 2-year overall, disease-free, distant metastasis-free survival and locoregional control. CONCLUSION: This is the first clinical study in which the diagnostic, predictive and prognostic roles of hypoxia-related biomolecules were examined in laryngeal neoplasms. Hypoxia-inducible factor-2 is a prognostic factor in larynx cancer irrespective of treatment modality.
Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/sangue , Biomarcadores Tumorais/sangue , Neoplasias Laríngeas/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Humanos , Hipóxia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos ProspectivosRESUMO
Recent studies have described the dichotomous function of IL-9 in various cancer diseases. However, its function has still not been analysed in laryngeal squamous cell carcinoma (LSCC). In the present study, we evaluated five single nucleotide polymorphisms (SNPs) of IL-9 (rs1859430, rs2069870, rs11741137, rs2069885, and rs2069884) and determined their associations with the patients' five-year survival rate. Additionally, we analysed serum IL-9 levels using an enzyme-linked immunosorbent assay. Three hundred LSCC patients and 533 control subjects were included in this study. A significant association between the patients' survival rate and distribution of IL-9 rs1859430 variants was revealed: patients carrying AA genotype had a higher risk of dying (p = 0.005). Haplotypes A-G-C-G-G of IL-9 (rs1859430, rs2069870, rs11741137, rs2069885, and rs2069884) were associated with 47% lower odds of LSCC occurrence (p = 0.035). Serum IL-9 levels were found detectable in three control group subjects (8.99 ± 12.03 pg/mL). In summary, these findings indicate that the genotypic distribution of IL-9 rs1859430 negatively influences the five-year survival rate of LSCC patients. The haplotypes A-G-C-G-G of IL-9 (rs1859430, rs2069870, rs11741137, rs2069885, and rs2069884) are associated with the lower odds of LSCC development.
Assuntos
Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/mortalidade , Predisposição Genética para Doença , Interleucina-9/sangue , Interleucina-9/genética , Neoplasias Laríngeas/sangue , Neoplasias Laríngeas/genética , Polimorfismo de Nucleotídeo Único/genética , Carcinoma de Células Escamosas/sangue , Estudos de Casos e Controles , Feminino , Frequência do Gene/genética , Haplótipos/genética , Humanos , Desequilíbrio de Ligação/genética , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , Taxa de SobrevidaRESUMO
Aims: To investigate the prognostic relevance of platelet volume indices for survival in laryngeal cancer. Patients & methods: The study included 640 patients with laryngeal cancer. We analyzed the optimal cutoff values through receiver operating characteristic analysis, then analyzed the univariate factor and multivariate variables. Kaplan-Meier curves and log-rank tests were conducted to compare the overall survival (OS) and recurrence-free survival rates between the groups. Results: In multivariate analysis, elevated platelet distribution width (PDW) and PDW/platelet count ratio were significantly correlated with poor prognosis for OS; however, elevated mean platelet volume (MPV) and MPV/platelet count ratio suggested a notable correlation with favorable prognosis for OS. Meanwhile, elevated PDW and decreased MPV were significantly correlated with poor prognosis for recurrence-free survival. Conclusions: Our findings indicate that elevated PDW and decreased MPV could serve as independent biomarkers for worse survival in laryngeal cancer.
Assuntos
Plaquetas/patologia , Neoplasias Laríngeas/sangue , Neoplasias Laríngeas/mortalidade , Idoso , Biomarcadores/sangue , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Volume Plaquetário Médio , Pessoa de Meia-Idade , Contagem de Plaquetas , Prognóstico , Curva ROC , Taxa de SobrevidaRESUMO
BACKGROUND: Although elevated serum gamma-glutamyltransferase (GGT) is a known indicator of increased risk of several cancers, the clinical value of repeated measurements of GGT has not been determined. Therefore, we aimed to investigate whether repeatedly elevated serum GGT levels are associated with the risk of respiratory cancer incidence. METHODS: We included participants who had undergone the Korean Health screening four times during 2009-2012 and had previously undergone four consecutive examinations. Those who were diagnosed with respiratory cancer before the date of examination were excluded. The participants obtained one GGT point if their GGT levels were in the highest quartile (the quartile 4 group). We analyzed the association between GGT points and respiratory cancer incidence by Cox proportional hazard models. RESULTS: During mean follow-up of 6.39 ± 1.2 years, 3,559,109 participants were enrolled. Of them, 8,944 (0.34%) men and 1,484 (0.14%) women were newly diagnosed with respiratory cancer. In multivariate analysis adjusted for confounding factors, male participants with 4 GGT points had a significantly higher hazards of developing respiratory cancer than those with 0 GGT points (hazard ratio [HR]: 1.39; 95% confidence interval [CI]: 1.31-1.48). Among female, participants with the highest points of GGT also had sixfold increased risk of developing laryngeal cancer. However, no significant association was observed between GGT points and lung cancer incidence among women (HR: 0.95; 95% CI: 0.81-1.11). CONCLUSION: Repeatedly elevated serum levels of GGT were associated with a higher risk of respiratory cancer incidence, especially in men. This finding suggests that physicians can identify a person with a higher risk of respiratory cancer through a simple repeated measurement of GGT.
Assuntos
Neoplasias Laríngeas/sangue , Neoplasias Pulmonares/sangue , gama-Glutamiltransferase/sangue , Adulto , Biomarcadores Tumorais/sangue , Estudos de Coortes , Feminino , Seguimentos , Humanos , Incidência , Neoplasias Laríngeas/enzimologia , Neoplasias Laríngeas/epidemiologia , Neoplasias Laríngeas/patologia , Neoplasias Pulmonares/enzimologia , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/patologia , Masculino , Prognóstico , República da Coreia/epidemiologia , Fatores de RiscoRESUMO
BACKGROUND: There were heterogeneous or even conflicting data regarding the ability of platelet-to-lymphocyte ratio (PLR) for predicting the prognosis of laryngeal/hypopharyngeal squamous cell carcinoma (LHSCC). The discrepancies were found to be largely due to the cutoff value of PLR. AIMS: The aims of this study were to rationally select an optimal PLR cutoff value and to analyze the relationship between pretreatment PLR and the prognosis. METHODS: A total of 180 male patients were eligible for this retrospective study. We included another 180 healthy male individuals as controls. The relationship between PLR and age in patients and the controls was determined. The optimal cutoff values of PLR were identified. PLR value was then dichotomized into two categories, and the relationship between PLR and the clinicopathologic parameters were calculated. Kaplan-Meier curves were used to evaluate the overall survival (OS), and the association between PLR and the OS was analyzed. RESULTS: The linear regression analysis showed a positive correlation between age and PLR in the control group, but not the patients. The optimal cutoff value of PLR was 112.5. The high PLR value group of patients exhibited significantly decreased OS. PLR was related to prognosis, as revealed by the univariate Cox regression. CONCLUSION: Patients with LHSCC have abnormal high PLR, and a high pretreatment PLR portends adverse survival.
Assuntos
Carcinoma de Células Escamosas/sangue , Neoplasias Hipofaríngeas/sangue , Neoplasias Laríngeas/sangue , Contagem de Linfócitos , Contagem de Plaquetas , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/cirurgia , Humanos , Neoplasias Hipofaríngeas/mortalidade , Neoplasias Hipofaríngeas/cirurgia , Estimativa de Kaplan-Meier , Neoplasias Laríngeas/mortalidade , Neoplasias Laríngeas/cirurgia , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Valores de Referência , Estudos RetrospectivosRESUMO
BACKGROUND/AIM: Prognosis of advanced stages of laryngeal squamous cell carcinoma (LSCC) remains poor. To clarify therapeutic targets and improve survival rate, identification of new specific and prognostic biomarkers of LSCC is required. The study aimed to evaluate the impact of IL-10:rs1800871, rs1800872, rs1800896 single nucleotide polymorphisms (SNPs), and IL-10 serum levels on LSCC development and determine associations of selected SNPs with patient survival rate. PATIENTS AND METHODS: A total of 300 LSCC patients and 533 controls were included in the study. Genotyping was carried out using RT-PCR; IL-10 serum levels were analyzed by ELISA. RESULTS: Significant associations were identified between IL-10 rs1800871 variants and advanced stage of LSCC patient group in the codominant, recessive and additive models (OR=0.473, p=0.027; OR=0.510, p=0.040; and OR=0.733; p=0.037). Significant variants of IL-10 rs1800872 were determined in the codominant, recessive and additive models (OR=0.473, p=0.027; OR=0.510, p=0.040; and OR=0.733, p=0.037). The distribution of IL-10 SNPs genotypes did not impact LSCC patient survival rate (respectively, p=0.952; p=0.952; p=0.991). CONCLUSION: IL-10:rs1800871 and rs1800872 SNPs are associated with advanced stage of LSCC. The genotypic distribution of IL-10 SNPs does not influence the survival rate of LSCC patients.
Assuntos
Interleucina-10/sangue , Interleucina-10/genética , Neoplasias Laríngeas/sangue , Neoplasias Laríngeas/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/sangue , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Feminino , Humanos , Neoplasias Laríngeas/mortalidade , Neoplasias Laríngeas/patologia , Masculino , Polimorfismo Genético , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Taxa de SobrevidaRESUMO
OBJECTIVES: Treatment effects in patients with laryngeal squamous cell carcinoma may vary significantly even among those with the same TNM stage. Routine preoperative blood and coagulation tests are economical and easily available hematological indicators. This study aimed to investigate the clinical predictive significance of pretreatment evaluation of plasma fibrinogen (FIB) level, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) in patients with laryngeal carcinoma. METHODS: Clinicopathological and demographic data from 203 patients who underwent surgery for laryngeal carcinoma were collected and analyzed. The optimal cutoff values for FIB, NLR, and PLR were determined using receiver operating characteristic curve analysis. Univariate and multivariate Cox regression analyses were used to study the relationship between blood markers and patient survival. RESULTS: The optimal cutoff values for FIB, NLR, and PLR were 3.05 g/L, 2.41, and 110.94, respectively. Preoperative hyperfibrinemia (FIB >3.05 g/L) was an independent prognostic factor for overall survival (OS) and disease-free survival in patients with laryngeal carcinoma. An NLR >2.41 was associated with reduced OS in patients with laryngeal carcinoma, while PLR >110.94 had no effect on prognosis in these patients. CONCLUSIONS: Fibrinogen and NLR were valuable markers in predicting survival in patients with laryngeal carcinoma and may be used to inform clinicians in designing individual treatment strategies.
Assuntos
Carcinoma de Células Escamosas/sangue , Fibrinogênio/análise , Neoplasias Laríngeas/sangue , Linfócitos , Neutrófilos , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Carcinoma de Células Escamosas/mortalidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Laríngeas/mortalidade , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Curva ROCRESUMO
PURPOSE: To explore the concentration of squamous cell carcinoma antigen (SCCA), cytokeratin fragment antigen 21-1 (CYFRA21-1) in patients with laryngeal squamous cell carcinoma (LSCC) and its correlation with tumorigenesis and progression. METHODS: A total of 78 patients with LSCC admitted to our hospital from February 2010 to January 2016 were enrolled as the research group (RG), and another 41 healthy volunteers from the same period were selected as the control group (CG). The serum concentrations of SCCA and CYFRA21-1 in patients with LSCC were detected by ELISA, whose diagnostic value in LSCC were further analyzed by ROC curve. The prognosis and survival curves of patients with LSCC were observed according to the median value of serum SCCA and CYFRA21-1 concentrations. RESULTS: The concentration of CYFRA21-1 and SCCA in the RG was significantly higher than that in the CG (p < 0.050). The SCCA and CYFRA21-1 identified a significant difference in smoking, lymphatic metastasis, TNM staging, and differentiation degree (p < 0.050). The survival rate of the SCCA low-concentration group was significantly better than that of the high-concentration group, p < 0.050. The survival rate of the CYFRA21-1 low-concentration group was markedly better than that of the high-concentration group, p < 0.050. CONCLUSIONS: SCCA and CYFRA21-1 are highly concentrated in LSCC patients, which have good diagnostic efficacy for LSCC. In addition, they play some certain role in the occurrence and development of LSCC, and are expected to be markers for early diagnosis and prognosis of this disease.
Assuntos
Antígenos de Neoplasias/sangue , Queratina-19/sangue , Neoplasias Laríngeas/sangue , Serpinas/sangue , Carcinoma de Células Escamosas de Cabeça e Pescoço/sangue , Biomarcadores Tumorais/sangue , Carcinogênese , Estudos de Casos e Controles , Progressão da Doença , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Neoplasias Laríngeas/etiologia , Neoplasias Laríngeas/mortalidade , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Curva ROC , Fumar/sangue , Carcinoma de Células Escamosas de Cabeça e Pescoço/etiologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Taxa de SobrevidaRESUMO
The aim is to estimate the prognostic value of lactate dehydrogenase (LDH) in patients undergoing surgical resection for laryngeal squamous cell carcinoma (LSCC). A total of 640 resected LSCC patients were included. Preoperative lactate dehydrogenase (LDH) was assessed. Kaplan-Meier survival analysis and Cox regression analysis were conducted for overall survival (OS) and recurrence-free survival (RFS). Kaplan-Meier analysis, univariate analysis and multivariate analysis demonstrated significant prognostic value for preoperative LDH. Although LDH was predictor of OS, it failed to be a predictor of RFS. The univariate HR and 95% CI of LDH were 0.484 and 0.357-0.658 (P < 0.0001). The multivariate analysis showed that LDH (HR = 0.518, 95% CI: 0.380-0.705, p < 0.0001) was related to OS. Elevated preoperative LDH >132 IU/L was significantly associated with better survival. Preoperative LDH might be an independent prognostic marker of OS in LSCC patients undergoing surgical resection.
Assuntos
Biomarcadores Tumorais/sangue , L-Lactato Desidrogenase/sangue , Neoplasias Laríngeas/mortalidade , Recidiva Local de Neoplasia/epidemiologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Idoso , Intervalo Livre de Doença , Estudos de Viabilidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Laríngeas/sangue , Neoplasias Laríngeas/cirurgia , Laringectomia/estatística & dados numéricos , Laringe/patologia , Laringe/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/prevenção & controle , Valor Preditivo dos Testes , Período Pré-Operatório , Prognóstico , Curva ROC , Estudos Retrospectivos , Medição de Risco/métodos , Medição de Risco/estatística & dados numéricos , Carcinoma de Células Escamosas de Cabeça e Pescoço/sangue , Carcinoma de Células Escamosas de Cabeça e Pescoço/cirurgiaRESUMO
OBJECTIVES: The study was designed to evaluate the tissue expression of NRP-1 and serum level of sNRP-1 in the same patients with intraepithelial laryngeal lesions or early staged laryngeal cancer to identify the clinical significance of these biomarkers in the diagnosis of laryngeal lesions. MATERIAL AND METHODS: A prospective analysis of tissue was performed on specimens and blood samples from 49 patients, who were admitted for surgical resection due to suspicious vocal fold lesions and were diagnosed as non-dysplasia, low-grade dysplasia, high-grade dysplasia and invasive cancers. RESULTS: ELISA was conducted on 48 blood samples. The minimum level of sNRP-1 was 0.15 ng/ml and maximum- 37.71 ng/ml. The Kruskal-Wallis one-way analysis of variance revealed no differences in sNRP-1 levels between different histopathological stages of vocal fold lesions (p = 0.234). IHC was conducted in 49 tissue samples. The evaluated mean scores of NRP-1 tissue expression were compared to histopathological stage of the lesion. The Kruskal-Wallis one-way analysis of variance revealed no differences in NRP-1 tissue expression between different histopathological stages of vocal fold lesions (p = 0.536). The correlation of tissue NRP-1 expression and serum levels of NRP-1 within analyzed group was insignificant. The Spearman's rank correlation coefficient was 0.076 (p = 0.606). CONCLUSIONS: The NRP-1 tissue expression and serum levels are unlikely to be a prognostic factor for identification of laryngeal dysplasia or early stage laryngeal cancer. Further studies investigating biomolecules involved in laryngeal carcinogenesis are necessary.