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1.
Biomed Res Int ; 2022: 2067540, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35036428

RESUMO

BACKGROUND: This study is aimed at constructing a risk signature to predict survival outcomes of ORCA patients. METHODS: We identified differentially expressed autophagy-related genes (DEARGs) based on the RNA sequencing data in the TCGA database; then, four independent survival-related ARGs were identified to construct an autophagy-associated signature for survival prediction of ORCA patients. The validity and robustness of the prognostic model were validated by clinicopathological data and survival data. Subsequently, four independent prognostic DEARGs that composed the model were evaluated individually. RESULTS: The expressions of 232 autophagy-related genes (ARGs) in 127 ORCA and 13 control tissues were compared, and 36 DEARGs were filtered out. We performed functional enrichment analysis and constructed protein-protein interaction network for 36 DEARGs. Univariate and multivariate Cox regression analyses were adopted for searching prognostic ARGs, and an autophagy-associated signature for ORCA patients was constructed. Eventually, 4 desirable independent survival-related ARGs (WDR45, MAPK9, VEGFA, and ATIC) were confirmed and comprised the prognostic model. We made use of multiple ways to verify the accuracy of the novel autophagy-related signature for survival evaluation, such as receiver-operator characteristic curve, Kaplan-Meier plotter, and clinicopathological correlational analyses. Four independent prognostic DEARGs that formed the model were also associated with the prognosis of ORCA patients. CONCLUSIONS: The autophagy-related risk model can evaluate OS for ORCA patients independently since it is accurate and stable. Four prognostic ARGs that composed the model can be studied deeply for target treatment.


Assuntos
Autofagia , Biomarcadores Tumorais , Modelos Biológicos , Neoplasias Bucais , Proteínas de Neoplasias , Nomogramas , Transcriptoma , Biomarcadores Tumorais/biossíntese , Biomarcadores Tumorais/genética , Bases de Dados de Ácidos Nucleicos , Intervalo Livre de Doença , Humanos , Neoplasias Bucais/genética , Neoplasias Bucais/metabolismo , Neoplasias Bucais/mortalidade , Proteínas de Neoplasias/biossíntese , Proteínas de Neoplasias/genética , Taxa de Sobrevida
2.
J Clin Oncol ; 40(3): 272-281, 2022 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-34871101

RESUMO

PURPOSE: The objective of this study was to explore the potential role and safety of neoadjuvant chemotherapy (NACT) in tumor shrinkage and resultant mandibular preservation in oral cancers compared with conventional surgical treatment. METHODS: This study was a single-center, randomized, phase II trial of treatment-naive histologically confirmed squamous cell carcinoma of the oral cavity with cT2-T4 and N0/N+, M0 (American Joint Committee on Cancer, seventh edition) stage, necessitating resection of the mandible for paramandibular disease in the absence of clinicoradiologic evidence of bone erosion. The patients were randomly assigned (1:1) to either upfront surgery (segmental resection) followed by adjuvant treatment (standard arm [SA]) or two cycles of NACT (docetaxel, cisplatin, and fluorouracil) at 3-week intervals (intervention arm [IA]), followed by surgery dictated by postchemotherapy disease extent. All patients in the IA received adjuvant chemoradiotherapy, and patients in the SA were treated as per final histopathology report. The primary end point was mandible preservation rate. The secondary end points were disease-free survival and treatment-related toxicity. RESULTS: Sixty-eight patients were enrolled over 3 years and randomly assigned to either SA (34 patients) or IA (34 patients). The median follow-up was 3.6 years (interquartile range, 0.95-7.05 years). Mandibular preservation was achieved in 16 of 34 patients (47% [95% CI, 31.49 to 63.24]) in the IA. The disease-free survival (P = .715, hazard ratio 0.911 [95% CI, 0.516 to 1.607]) and overall survival (P = .747, hazard ratio 0.899 [95% CI, 0.510 to 1.587]) were similar in both the arms. Complications were similar in both arms, but chemotherapy-induced toxicity was observed in the majority of patients (grade III: 14, 41.2%; grade IV: 11, 32.4%) in the IA. CONCLUSION: NACT plays a potential role in mandibular preservation in oral cancers with acceptable toxicities and no compromise in survival. However, this needs to be validated in a larger phase III randomized trial.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Mandíbula/cirurgia , Osteotomia Mandibular , Neoplasias Bucais/terapia , Terapia Neoadjuvante , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimiorradioterapia Adjuvante , Quimioterapia Adjuvante , Cisplatino/uso terapêutico , Progressão da Doença , Docetaxel/uso terapêutico , Feminino , Fluoruracila/uso terapêutico , Humanos , Índia , Masculino , Mandíbula/patologia , Osteotomia Mandibular/efeitos adversos , Osteotomia Mandibular/mortalidade , Pessoa de Meia-Idade , Neoplasias Bucais/mortalidade , Neoplasias Bucais/patologia , Terapia Neoadjuvante/efeitos adversos , Terapia Neoadjuvante/mortalidade , Intervalo Livre de Progressão , Estudos Prospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Fatores de Tempo , Carga Tumoral
3.
Anticancer Res ; 42(1): 97-104, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34969714

RESUMO

BACKGROUND/AIM: We compared postoperative radiotherapy (PORT) to surgery only (SO), and supraomohyoidal neck dissection (SOHND) to modified radical neck dissection (MRND) in patients with pT1-T2 squamous cell carcinomas of the oral cavity (OSCC) and a single cervical lymph node metastasis (pN1) in terms of overall survival (OS), oral cancer specific survival (OCSS), and regional recurrence-free survival (RRFS), in a prospective cohort study. PATIENTS AND METHODS: We included patients with pT1-T2 pN1 OSCC with no distant metastasis and estimated the survival probabilities using the Kaplan-Meier method and calculated hazards ratios (HR) for PORT vs. SO and MRND vs. SOHND using adjusted Cox regression models. RESULTS: A total of 51 patients (26 SO vs. 25 PORT, 9 SOHND vs. 42 MRND) were evaluated. Patients who received PORT were more likely to be younger and healthier. OS at 5 years was 41% and 87% in the SO and PORT groups, respectively. OS at 5 years was 52% and 67% in the in the SOHND and MRND groups, respectively. Both OCSS and RRFS were improved by PORT. Extending neck dissection was not associated with improved OS (HR = 0.83). CONCLUSION: PORT is associated with preferable OS, OCSS, and RRFS in pT1-2 pN1 oral cancer and should be recommended regularly.


Assuntos
Carcinoma de Células Escamosas/radioterapia , Linfonodos/patologia , Neoplasias Bucais/radioterapia , Esvaziamento Cervical/métodos , Radioterapia Adjuvante/métodos , Idoso , Carcinoma de Células Escamosas/mortalidade , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/mortalidade , Metástase Neoplásica , Estudos Prospectivos , Análise de Sobrevida
4.
BMC Cancer ; 21(1): 1309, 2021 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-34876079

RESUMO

BACKGROUND: Treatment of clinical N0 neck tumours is controversial in early-stage oral squamous cell carcinoma (OSCC), possibly because T1N0M0 and T2N0M0 merge together at early stages. The purposes of this study were to compare survival outcomes only for T2N0M0 cases based upon treatment elective neck dissection versus neck observation. METHODS: T2N0M0 OSCC cases were identified in the Surveillance, Epidemiology, and End Results database of the United States National Cancer Institute between 2004 and 2015. Survival curves for different variable values were generated using Kaplan-Meier estimates and compared using the log-rank test. Variables that achieved significance at P < 0.05 were entered into multivariable analyses via the Cox proportional hazards multivariate regression. RESULTS: A total of 2857 patients were selected, and 2313 cases were available for disease specific survival (DSS). The 5-year and 10-year overall survival (OS) were 66.7 and 46% for patients receiving elective neck dissection (END), respectively, and 56.4 and 37.2% for patients with neck observation (P < 0.0001). The 5-year and 10-year DSS were 73.6 and 64% for the END group, respectively, versus 64.5 and 54.5% for the neck observation group (P < 0.0001). More importantly, performing END was independently associated with favourable DSS and OS for patients with T2N0M0 OSCC [hazard ratio (HR) = 0.769, P = 0.0069 for DSS; HR = 0.829, P = 0.0031 for OS, neck observation group as reference] according to multivariate survival analysis. CONCLUSION: END is recommended for T2N0M0 OSCC cases and it is associated with improved DSS and OS.


Assuntos
Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/terapia , Neoplasias Bucais/mortalidade , Neoplasias Bucais/terapia , Esvaziamento Cervical/mortalidade , Conduta Expectante/estatística & dados numéricos , Idoso , Carcinoma de Células Escamosas/patologia , Procedimentos Cirúrgicos Eletivos/métodos , Procedimentos Cirúrgicos Eletivos/mortalidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/patologia , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Programa de SEER , Análise de Sobrevida
5.
Biomed Res Int ; 2021: 5436894, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34904115

RESUMO

BACKGROUND: Cancer is primarily caused by smoking, alcohol, betel quit, a series of genetic alterations, and epigenetic abnormalities in signaling pathways, which result in a variety of phenotypes that favor the development of OSCC. Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer, accounting for 80-90% of all oral malignant neoplasms. Oral cancer is relatively common, and it is frequently curable when detected and treated early enough. The tumor-node-metastasis (TNM) staging system is used to determine patient prognosis; however, geographical inaccuracies frequently occur, affecting management. OBJECTIVE: To determine the additional relationship between factors discovered by searching for sociodemographic and metastasis factors, as well as treatment outcomes, which could help improve the prediction of the survival rate in cancer patients. Material and Methods. A total of 56 patients were recruited from the ambulatory clinic at the Hospital Universiti Sains Malaysia (USM). In this retrospective study, advanced computational statistical modeling techniques were used to evaluate data descriptions of several variables such as treatment, age, and distant metastasis. The R-Studio software and syntax were used to implement and test the hazard ratio. The statistics for each sample were calculated using a combination model that included methods such as bootstrap and multiple linear regression (MLR). RESULTS: The statistical strategy showed R demonstrates that regression modeling outperforms an R-squared. It demonstrated that when data is partitioned into a training and testing dataset, the hybrid model technique performs better at predicting the outcome. The variable validation was determined using the well-established bootstrap-integrated MLR technique. In this case, three variables are considered: age, treatment, and distant metastases. It is important to note that three things affect the hazard ratio: age (ß 1: -0.006423; p < 2e - 16), treatment (ß 2: -0.355389; p < 2e - 16), and distant metastasis (ß 3: -0.355389; p < 2e - 16). There is a 0.003469102 MSE for the linear model in this scenario. CONCLUSION: In this study, a hybrid approach combining bootstrapping and multiple linear regression will be developed and extensively tested. The R syntax for this methodology was designed to ensure that the researcher completely understood the illustration. In this case, a hybrid model demonstrates how this critical conclusion enables us to better understand the utility and relative contribution of the hybrid method to the outcome. The statistical technique used in this study, R, demonstrates that regression modeling outperforms R-squared values of 0.9014 and 0.00882 for the predicted mean squared error, respectively. The conclusion of the study establishes the superiority of the hybrid model technique used in the study.


Assuntos
Sobrevivência Celular/fisiologia , Neoplasias Bucais/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Humanos , Modelos Lineares , Metástase Linfática/patologia , Malásia , Neoplasias Bucais/patologia , Análise Multivariada , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Taxa de Sobrevida
6.
BMC Cancer ; 21(1): 1327, 2021 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-34903206

RESUMO

BACKGROUND: It is a basic task in high-throughput gene expression profiling studies to identify differentially expressed genes (DEGs) between two phenotypes. RankComp, an algorithm, could analyze the highly stable within-sample relative expression orderings (REOs) of gene pairs in a particular type of human normal tissue that are widely reversed in the cancer condition, thereby detecting DEGs for individual disease samples measured by a particular platform. METHODS: In the present study, Gene Expression Omnibus (GEO) Series (GSE) GSE75540, GSE138206 were downloaded from GEO, by analyzing DEGs in oral squamous cell carcinoma based on online datasets using the RankComp algorithm, using the Kaplan-Meier survival analysis and Cox regression analysis to survival analysis, Gene Set Enrichment Analysis (GSEA) to explore the potential molecular mechanisms underlying. RESULTS: We identified 6 reverse gene pairs with stable REOs. All the 12 genes in these 6 reverse gene pairs have been reported to be associated with cancers. Notably, lower Interferon Induced Protein 44 Like (IFI44L) expression was associated with poorer overall survival (OS) and Disease-free survival (DFS) in oral squamous cell carcinoma patients, and IFI44L expression showed satisfactory predictive efficiency by receiver operating characteristic (ROC) curve. Moreover, low IFI44L expression was identified as risk factors for oral squamous cell carcinoma patients' OS. IFI44L downregulation would lead to the activation of the FRS-mediated FGFR1, FGFR3, and downstream signaling pathways, and might play a role in the PI3K-FGFR cascades. CONCLUSIONS: Collectively, we identified 6 reverse gene pairs with stable REOs in oral squamous cell carcinoma, which might serve as gene signatures playing a role in the diagnosis in oral squamous cell carcinoma. Moreover, high expression of IFI44L, one of the DEGs in the 6 reverse gene pairs, might be associated with favorable prognosis in oral squamous cell carcinoma patients and serve as a tumor suppressor by acting on the FRS-mediated FGFR signaling.


Assuntos
Neoplasias Bucais , Carcinoma de Células Escamosas de Cabeça e Pescoço , Proteínas Supressoras de Tumor , Regulação para Baixo/genética , Feminino , Humanos , Masculino , Neoplasias Bucais/diagnóstico , Neoplasias Bucais/genética , Neoplasias Bucais/metabolismo , Neoplasias Bucais/mortalidade , Prognóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico , 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/mortalidade , Transcriptoma/genética , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo
7.
Cell Rep Med ; 2(10): 100426, 2021 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-34755137

RESUMO

Oral cavity squamous cell carcinoma (OCSCC) is a prevalent surgically treated subset of head and neck cancer with frequent recurrence and poor survival. Immunotherapy has demonstrated efficacy in recurrent/metastatic head and neck cancer. However, whether antitumor responses could be fostered by neoadjuvant presurgical immunotherapy remains unclear. Using a Simon's two-stage design, we present results of a single-arm phase-II trial where 12 patients with stage II-IVA OCSCC received 3 to 4 biweekly doses of 3 mg/kg nivolumab followed by definitive surgical resection with curative intent. Presurgical nivolumab therapy in this cohort shows an overall response rate of 33% (n = 4 patients; 95% CI: 12%-53%). With a median follow up of 2.23 years, 10 out of 12 treated patients remain alive. Neoadjuvant nivolumab is safe, well-tolerated, and is not associated with delays in definitive surgical treatment in this study. This work demonstrates feasibility and safety for incorporation of nivolumab in the neoadjuvant setting for OCSCC (ClinicalTrials.gov: NCT03021993).


Assuntos
Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias Bucais/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Nivolumabe/uso terapêutico , Receptor de Morte Celular Programada 1/genética , Idoso , Antineoplásicos Imunológicos/uso terapêutico , Carcinoma de Células Escamosas/imunologia , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/cirurgia , Estudos de Coortes , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/imunologia , Neoplasias Bucais/mortalidade , Neoplasias Bucais/cirurgia , Terapia Neoadjuvante/métodos , Recidiva Local de Neoplasia/imunologia , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/cirurgia , Estadiamento de Neoplasias , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , Análise de Sobrevida , Resultado do Tratamento
8.
Anticancer Res ; 41(11): 5405-5413, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34732409

RESUMO

BACKGROUND/AIM: Oral squamous cell carcinoma (OSCC) is a highly invasive malignancy with poor prognosis. Recent reports suggest that Sonic Hedgehog (SHH) plays a key role in tumor progression and worsens the response to therapy, possibly through an association with a cancer stem cell (CSC) phenotype. The objective of our study was to investigate the relationship between SHH expression and CSC markers in OSCC. MATERIALS AND METHODS: A total of 67 OSCC specimens were immunostained for SHH and CSC markers using specific antibodies and expression was correlated with clinicopathological parameters. RESULTS: SHH expression was significantly correlated with CD133 (p=0.026, r=0.272) and SRY-box transcription factor 2 (SOX2; p<0.001, r=0.793). SHH and SOX2 expression were associated with worse survival in OSCC (p=0.003 and p=0.003, respectively). In multivariate analysis SHH and CD44 were independent prognostic biomarkers in patients with OSCC (p=0.001 and p=0.008, respectively). CONCLUSION: Our study revealed that SHH overexpression is closely associated with CSC markers, contributing to tumor progression and worse outcomes of patients with OSCC.


Assuntos
Biomarcadores Tumorais/análise , Proteínas Hedgehog/análise , Neoplasias Bucais/química , Células-Tronco Neoplásicas/química , Carcinoma de Células Escamosas de Cabeça e Pescoço/química , Antígeno AC133/análise , Progressão da Doença , Feminino , Humanos , Receptores de Hialuronatos/análise , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/mortalidade , Neoplasias Bucais/patologia , Neoplasias Bucais/cirurgia , Células-Tronco Neoplásicas/patologia , Estudos Retrospectivos , Fatores de Transcrição SOXB1/análise , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/cirurgia , Resultado do Tratamento
9.
Anticancer Res ; 41(11): 5785-5791, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34732452

RESUMO

BACKGROUND/AIM: This study was conducted to compare the efficacy and safety of the weekly cetuximab plus paclitaxel (wCmab-PTX) regimen with those of the EXTREME regimen in patients with recurrent or metastatic oral squamous cell carcinoma (R/M OSCC). PATIENTS AND METHODS: This multicenter retrospective study involved a chart review of the clinical records of R/M OSCC patients treated with wCmab-PTX in each institution between January 2013 and December 2017. Data were collected, and the efficacy, safety, and treatment outcomes were analyzed. RESULTS: The best overall response and disease control rates were 48.4% and 61.3%, respectively. The median PFS and OS were 6 and 13 months, respectively. There was no significant difference in prognosis with or without previous platinum administration. The grade 3-4 adverse events were leukopenia (16.1%), followed by acne-like rash (12.9%), and neutropenia (9.7%). All adverse events, excluding more than grade 3 infusion reactions, were tolerable and manageable. CONCLUSION: wCmab-PTX may be considered as a treatment option for R/M patients with OSCC that is refractory to platinum-based chemotherapy, or progressive disease after receiving chemotherapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Cetuximab/administração & dosagem , Neoplasias Bucais/tratamento farmacológico , Recidiva Local de Neoplasia , Paclitaxel/administração & dosagem , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cetuximab/efeitos adversos , Progressão da Doença , Esquema de Medicação , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/mortalidade , Neoplasias Bucais/patologia , Paclitaxel/efeitos adversos , Intervalo Livre de Progressão , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/secundário , Fatores de Tempo
10.
Sci Rep ; 11(1): 22273, 2021 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-34782680

RESUMO

The distribution of lip, oral cavity, and pharynx (LOCP) cancer mortality rates in small domains (defined as the combination of province, age group, and gender) remains unknown in Spain. As many of the LOCP risk factors are preventable, specific prevention programmes could be implemented but this requires a clear specification of the target population. This paper provides an in-depth description of LOCP mortality rates by province, age group and gender, giving a complete overview of the disease. This study also presents a methodological challenge. As the number of LOCP cancer cases in small domains (province, age groups and gender) is scarce, univariate spatial models do not provide reliable results or are even impossible to fit. In view of the close link between LOCP and lung cancer, we consider analyzing them jointly by using shared component models. These models allow information-borrowing among diseases, ultimately providing the analysis of cancer sites with few cases at a very disaggregated level. Results show that males have higher mortality rates than females and these rates increase with age. Regions located in the north of Spain show the highest LOCP cancer mortality rates.


Assuntos
Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias Pulmonares/mortalidade , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Feminino , Geografia Médica , Neoplasias de Cabeça e Pescoço/epidemiologia , Humanos , Neoplasias Labiais/epidemiologia , Neoplasias Labiais/mortalidade , Neoplasias Pulmonares/epidemiologia , Masculino , Modelos Teóricos , Neoplasias Bucais/epidemiologia , Neoplasias Bucais/mortalidade , Neoplasias Faríngeas/epidemiologia , Neoplasias Faríngeas/mortalidade , Vigilância da População , Fatores de Risco , Espanha/epidemiologia , Análise Espacial
11.
Sci Rep ; 11(1): 19770, 2021 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-34611254

RESUMO

Postoperative adjuvant therapy has been indicated by advanced T classification for T3-4 oral squamous cell carcinoma (OSCC) and the significance of perineural invasion (PNI) and lymphovascular invasion (LVI) in treatment for T3-4 OSCC remains unclear. Ninety-eight cumulative patients with T3-4 OSCC who underwent curative surgery between Jan 2002 and Dec 2010 were recruited and analyzed. Twenty-seven (27.6%) patients were PNI/LVI double positive. PNI/LVI double positive demonstrated independent predictive values for higher neck metastasis (LN+), higher distant metastasis (DM) and low 5-year disease-specific survival (DSS) rates (p < 0.001, p = 0.017, and p < 0.001, respectively) after controlling for other pathologic features of the primary tumors. A high DM rate of 33.3% was noted in PNI/LVI double-positive patients. Among the PNI/LVI double negative, single positive to double positive subgroups, increasing LN+, DM rates and decreasing DSS rate were observed. Among the 44 LN+ patients, PNI/LVI double positive remained associated with a markedly high DM rate of 42.9% and a poor 5-year DSS of 27.7%. PNI/LVI double positive plays important roles in prognostication and potential clinical application for T3-4 OSCC by independently predicting LN+, DM, and poor DSS, and can be used as a good marker to select DM high-risk patients for novel adjuvant therapy trials.


Assuntos
Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Neoplasias Bucais/mortalidade , Neoplasias Bucais/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/terapia , Feminino , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/terapia , Análise Multivariada , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , Vigilância em Saúde Pública , Análise de Sobrevida
12.
Int J Biol Sci ; 17(13): 3476-3492, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34512160

RESUMO

Ferroptosis is a newly recognized mechanism of regulated cell death. It was reported to be highly associated with immune therapy and chemotherapy. However, its mechanism of regulation in the tumor microenvironment (TME) and influence on oral squamous cell carcinoma (OSCC) therapy are unknown. We identified a ferroptosis-specific gene-expression signature, an FPscore, developed by a principal component analysis (PCA) algorithm to evaluate the ferroptosis regulation patterns of individual tumor. Multi-omics analysis of ferroptosis regulation patterns was conducted. Three distinct ferroptosis regulation subtypes, which linked to outcomes and the clinical relevance of each patient, were established. A high FPscore of patients with OSCC was associated with a favorable prognosis, a ferroptosis-related immune-activation phenotype, potential sensitivities to the chemotherapy and immunotherapy. Importantly, a high FPscore correlated with a low gene copy number burden and high immune checkpoint expressions. We validated the prognostic value of the FPscore using independent immunotherapy and pan-cancer cohorts. Comprehensive evaluation of individual tumors with distinct ferroptosis regulation patterns provides new mechanistic insights, which may be clinically relevant for the application of combination therapies in OSCC.


Assuntos
Ferroptose , Neoplasias Bucais/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Transcriptoma , Microambiente Tumoral , Biomarcadores Tumorais/metabolismo , Estudos de Casos e Controles , Variações do Número de Cópias de DNA , Humanos , Neoplasias Bucais/mortalidade , Neoplasias Bucais/terapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia
13.
Medicine (Baltimore) ; 100(36): e27127, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34516504

RESUMO

ABSTRACT: In Malaysia, oral cancer is very common and the reported 5-year survival of such patients is nearly 50% after treatment with surgery and radiotherapy, much lower than most of the developed countries. This study aimed to investigate the socio-demographic and clinicopathological parameters that influence the mortality rate of the patients suffering from oral squamous cell carcinoma (OSCC) in the Kelantanse population.In this retrospective study, data regarding socio-demographic, clinicopathological factors, and treatment outcome associated with OSCC were gathered from the archives of the medical records office of Hospital Universiti Sains Malaysia. For statistical analysis, simple and multiple logistic regression were performed. The significance level was set to P < .25.A total of 211 OSCC cases were registered in Hospital Universiti Sains Malaysia from January 1, 2000 to December 31, 2018. Majority of them were male (57.82%), non-smoker (54.97%), non-alcohol consumer (91.94%), and non-betel quid chewer (93.83%) Malay (60.66%) patients. The tongue was the most commonly involved part of the oral cavity (41.52%). Histologically, the majority of the cases had moderately-differentiated OSCC (52.82%). Most of the patients were diagnosed at stage IV at the time of diagnosis (61.61%). When this study was performed, the survival status of the majority of the patients was alive (68.24%).Within the analyzed socio-demographic and clinicopathological parameters, gender, alcohol consumption, T-classification, histological grading, and treatment status have been demonstrated as an independent risk factors for mortality rate in multivariate analysis. Hence, these parameters need to be taken into account for the individualized therapy management of OSCC patients.


Assuntos
Carcinoma de Células Escamosas/mortalidade , Neoplasias Bucais/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/etiologia , Estudos Transversais , Feminino , Humanos , Malásia , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/etiologia , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Adulto Jovem
14.
Anticancer Res ; 41(9): 4515-4522, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34475077

RESUMO

BACKGROUND/AIM: The role of tumour-infiltrating CD45Ro+ T-cells in oral squamous cell carcinoma (OSCC) is unclear. This study aimed to evaluate prognostic biomarkers for OSCC. PATIENTS AND METHODS: We determined the density of tumour-infiltrating CD45Ro+ T cells in the parenchyma and stroma at the tumour centre (TCe) and invasive front (IF) and examined the association between the density of these cells and histopathological status in 142 patients. RESULTS: Five-year overall survival (OS) and recurrence-free survival were favourable in patients with high CD45Ro+ T-cell density in the TCe stroma. OS was favourable in patients with high CD45Ro+ T-cell density in the IF stroma. Stepwise Cox regression model analysis indicated that CD45Ro+ T-cells in the stroma of the IF and TCe were an independent prognostic factor for OS. CONCLUSION: CD45Ro+ T-cells in the stroma of the IF and TCe play a role in cancer immune surveillance and may be a useful prognostic factor.


Assuntos
Carcinoma de Células Escamosas/mortalidade , Antígenos Comuns de Leucócito/metabolismo , Linfócitos do Interstício Tumoral/imunologia , Neoplasias Bucais/mortalidade , Linfócitos T/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/imunologia , Prognóstico , Análise de Regressão , Estudos Retrospectivos , Análise de Sobrevida
15.
Bioengineered ; 12(1): 7248-7262, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34585646

RESUMO

RNA binding proteins (RBPs) play a pivotal role in various biological processes, and aberrant expression of RBPs is closely associated with tumorigenesis and progression. However, the role of RBPs in oral cavity squamous cell carcinoma (OCSCC) is yet unveiled. In this study, RNA sequences and clinical information of OCSCC samples were acquired from The Cancer Genome Atlas (TCGA) database. A total of 650 RBPs, with significantly different expression between healthy and OCSCC samples, were identified using the limma package. A prognostic model was constructed by Lasso-Cox analysis, resulting in the determination of 7 prognosis-related RBPs: ERMP1, RNASE3, ARL4D, CSRP2, ULK1, ZC3H12D, and RPS28. Based on the prognostic model, the risk scores of the OCSCC samples were calculated. The capability of the prognostic model was further evaluated using the receiver operating characteristic curve (ROC). The areas under ROC were 0.764, 0.771, and 0.809 at 1, 3 and 5-year respectively in the TCGA dataset. Internal and external validation showed satisfactory predictive capability for prognosis in OCSCC. In addition, a nomogram was created to graphically present the model. To further validate the analytical data, qRT-PCR was performed on normal and OCSCC cell lines. The mRNA expression of the 7 prognostic genes was in accordance with the analytical results. Functional analysis and gene connection networks were used to describe the biological functions and underlying interactions among the 7 prognostic genes Overall, 7 prognosis-related RBPs were identified, which could be used to predict clinical prognosis and to identify potential therapeutic targets for OCSCC.


Assuntos
Neoplasias Bucais , Proteínas de Ligação a RNA , Carcinoma de Células Escamosas de Cabeça e Pescoço , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Biologia Computacional , Perfilação da Expressão Gênica , Humanos , Neoplasias Bucais/diagnóstico , Neoplasias Bucais/genética , Neoplasias Bucais/metabolismo , Neoplasias Bucais/mortalidade , Prognóstico , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico , 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/mortalidade , Transcriptoma/genética
16.
Cancer Med ; 10(20): 6947-6958, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34558224

RESUMO

BACKGROUND: We compared the clinical outcomes of patients with oral cavity squamous cell carcinoma (OCSCC) with cN+pN0 versus cN0pN0 disease. METHODS: A total of 1309 OCSCC patients with pN0 disease were included. Of them, 1019 and 290 cases had cN0pN0 and cN+pN0 disease, respectively. For comparison purposes, we also examined 799 patients with pN+disease (cN0pN+/cN+pN+, n = 239/560). Subgroup analysis was performed in a propensity score-matched cohort with cN0pN0 and cN+pN0 disease (n = 284 each). RESULTS: Compared with cN0pN0, patients with cN+pN0 had a higher prevalence of the following variables: betel chewing, pT3-4, depth ≥10 mm, perineural invasion, and treatment with surgery and adjuvant therapy. The prognosis of patients with cN+pN0 (mean: 52 nodes) and cN0pN0 (mean: 39 nodes) disease was similar both in the original cohort and after propensity score matching. However, the 5-year outcomes were more favorable for cN+pN0/cN0pN0 compared with cN0pN+/cN+pN+ (local control, 88%/88%/83%/81%; neck control, 94%/93%/82%/76%; distant metastases, 4%/3%/13%/31%; disease-free survival, 84%/83%/68%/52%; disease-specific survival, 92%/92%/77%/57%; overall survival, 81%/82%/59%/42%; all p values <0.001; cN+pN0 versus cN0pN0, all p values >0.05). cN+pN0 disease (vs. cN0pN0) was not significantly associated with local control, neck control, distant metastases, and survivals either in univariable or multivariable analyses. CONCLUSIONS: Despite a higher risk factor burden, the prognosis of patients with cN+pN0 disease did not differ from that of cases with cN0pN0. The higher nodal yield and the more frequent use of adjuvant therapy in cN+pN0 disease may explain the lack of significant differences in terms of neck control compared with cN0pN0 disease.


Assuntos
Neoplasias Bucais/mortalidade , Neoplasias Bucais/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Idoso , Análise de Variância , Areca , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Humanos , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/cirurgia , Pescoço , Esvaziamento Cervical , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , Pontuação de Propensão , Radioterapia Adjuvante , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/cirurgia , Fatores de Tempo
17.
J Immunol Res ; 2021: 6203759, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34497859

RESUMO

BACKGROUND: Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer, which remains a major cause of morbidity and mortality in patients with head and neck cancers. However, the critical immune-related signatures and their prognostic values have rarely been investigated. MATERIALS AND METHODS: Gene differential analysis was used to measure the differences of gene expression between the groups. Correlation analysis was used to assess the association between the gene expression levels and immune-related risk score/DNA methylation levels. The gene set enrichment analysis (GSEA) was used to identify the pathways or cell types enriched by those identified differentially expressed genes (DEGs). RESULTS: In this study, we identified four immune-related gene signatures, including CTSG, TNFRSF4, LCORL, and PLAU, that were significantly associated with the overall survival in OSCC patients from the Cancer Genome Atlas (TCGA) OSCC cohort. Moreover, these four immune-related signatures were differentially expressed between the OSCC and nontumor tissues. The two groups (high and low risk) stratified by the immune-related risk scores had significantly different OS and mortality rates. The gene expression patterns and prognostic values of these immune-related signatures were also verified in two independent validation cohorts. Furthermore, the downregulated genes in the high-risk group (which were also upregulated in the low-risk group) were significantly enriched in the cell type-specific signatures of type 2 T helper cell (Th2), plasmacytoid dendritic cell (pDC), and memory B cell. In contrast, the upregulated genes in the high-score group were enriched in growth factor receptor-related signaling pathways, such as the VEGFA-VEGFR2 signaling pathway, PI3K-Akt signaling pathway, focal adhesion-PI3K-Akt-mTOR signaling pathway, and PDGF pathway, suggesting that those pathways were inversely correlated with immune cell infiltration. CONCLUSION: In summary, the immune-related signatures had the potential for predicting the risk of OSCC patients. Moreover, the present study also improved our understanding of the association between the growth factor receptor pathways and immune cell infiltration in OSCC.


Assuntos
Biomarcadores Tumorais/imunologia , Carcinoma de Células Escamosas/imunologia , Carcinoma de Células Escamosas/mortalidade , Suscetibilidade a Doenças/imunologia , Neoplasias Bucais/imunologia , Neoplasias Bucais/mortalidade , Animais , Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/diagnóstico , Biologia Computacional/métodos , Bases de Dados Genéticas , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Imunidade/genética , Masculino , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Transdução de Sinais , Transcriptoma
18.
BMC Cancer ; 21(1): 922, 2021 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-34391381

RESUMO

OBJECTIVE: Tongue and mouth floor squamous cell carcinoma (T/MF SCC) exhibits a high rate of local recurrence and cervical lymph node metastasis. The effect of the tumor microenvironment on T/MF SCC remains unclear. MATERIALS AND METHODS: Transcriptome and somatic mutation data of patients with T/MF SCC were obtained from HNSC projects of the Cancer Genome Atlas. Immune infiltration quantification in early- (clinical stage I-II) and advanced-stage (clinical stage III-IV) T/MF SCC was performed using single sample Gene Set Enrichment Analysis and MCPcounter. Differentially expressed gene data were filtered, and their function was assessed through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. Kaplan-Meier survival curve analysis and Cox regression model were conducted to evaluate the survival of patients with the CCL22 signature. Maftools was used to present the overview of somatic mutations. RESULTS: In T/MF SCC, T helper (Th)2 cell counts were significantly increased in patients with early-stage disease compared to those with advanced-stage disease. Expression of the Th2 cell-related chemokine, CCL22, was downregulated in patients with advanced-stage T/MF SCC. Univariate and multivariate Cox analyses revealed that CCL22 was a good prognostic factor in T/MF SCC. A nomogram based on the expression of CCL22 was constructed to serve as a prognostic indicator for T/MF SCC. NOTCH1 mutations were found at a higher rate in patients with advanced-stage T/MF SCC than in those with early-stage T/MF SCC, resulting in the inhibition of the activation of the NOTCH1-Th2 cell differentiation pathway. The expression levels of CCL22, GATA-3, and IL4 were higher in patients with early-stage T/MF SCC than in those with advanced-stage T/MF SCC. CONCLUSION: In T/MF SCC, high expression of CCL22 may promote the recruitment of Th2 cells and help predict a better survival. Mutations in NOTCH1 inhibit the differentiation of Th2 cells, facilitating tumor progression through a decrease in Th2 cell recruitment and differentiation.


Assuntos
Carcinoma de Células Escamosas/etiologia , Carcinoma de Células Escamosas/metabolismo , Quimiocina CCL22/genética , Neoplasias Bucais/etiologia , Neoplasias Bucais/metabolismo , Receptor Notch1/genética , Células Th2/imunologia , Células Th2/metabolismo , Adulto , Idoso , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Quimiotaxia de Leucócito/genética , Quimiotaxia de Leucócito/imunologia , Biologia Computacional/métodos , Feminino , Fator de Transcrição GATA3/genética , Fator de Transcrição GATA3/metabolismo , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Contagem de Linfócitos , Linfócitos do Interstício Tumoral , Masculino , Pessoa de Meia-Idade , Soalho Bucal/metabolismo , Soalho Bucal/patologia , Neoplasias Bucais/mortalidade , Neoplasias Bucais/patologia , Mutação , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais
19.
J Surg Oncol ; 124(8): 1284-1295, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34416792

RESUMO

BACKGROUND: Guidelines recommended for resection of oral cancer define a free margin of ≥5 mm as clear and safe (R0). This statement was questioned recently based on the assumption that different surgical margins may hold different risk categories. The aim of this study was to investigate the impact of stratification of the surgical margins on the survival outcome of patients with oral cancer. METHODS: In a cohort of 753 patients, the hazard ratio for local recurrence-free survival (LRFS), overall survival (OS), and oral cancer-specific survival (OCSS) were estimated for R0 resection, the close margin of 1-4 mm, involved resection borders but with free frozen sections. Competing risk factors were considered in the statistical regression model. RESULTS: One hundred seventy-three (23%) patients developed local recurrence and 316 (42%) died in the 5 follow-up years. There was a gradual improvement in the LRFS, OCSS, OS with the increase of clear margin. OS showed a similar tendency. CONCLUSION: Not all patients with an R0cm status carry the same risk for impaired LRFS, OCSS, and OS. Their risk to develop recurrence is higher than those patients with R0 ≥5 mm but stratified risk management can be recommended according to the presented results.


Assuntos
Carcinoma de Células Escamosas/mortalidade , Margens de Excisão , Neoplasias Bucais/mortalidade , Idoso , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/patologia , Neoplasias Bucais/cirurgia , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Taxa de Sobrevida
20.
JCO Precis Oncol ; 52021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34381934

RESUMO

Telomerase reverse transcriptase (TERT) promoter mutations are prognostic in many cancers and have been observed in human papillomavirus (HPV)-negative head and neck squamous cell carcinomas (HNSCCs). However, the role of TERT promoter mutations in HPV-negative HNSCCs remains poorly understood in these cancers, which have increased risk for locoregional failure (LRF). PATIENTS AND METHODS: We retrospectively identified patients who were diagnosed with HNSCC between July 1, 2004, and October 12, 2017, at Memorial Sloan Kettering Cancer Center and whose tumors underwent next-generation sequencing using the MSK-IMPACT panel. Patients with HPV-positive oropharyngeal squamous cell carcinoma (SCC) were excluded. Cumulative incidence of LRF, patterns of failure, and overall survival were measured. RESULTS: We identified 117 patients with SCC of the oral cavity (OSCC), larynx, hypopharynx, or HPV-negative oropharynx whose tumors underwent next-generation sequencing. Sequencing was performed on 95 tumors that were obtained after recurrence and 22 that were obtained before recurrence. TERT promoter mutations were enriched in OSCC compared with laryngopharyngeal cancers (81.1% v 7.0%; P < .001), which was the largest genetic difference between these anatomic disease subsites. TERT promoter mutations were associated with LRF in OSCCs (Gray's test, P < .001) and in the overall cohort (Gray's test, P < .001). On multivariate analysis, TERT promoter mutations were associated with an increased risk for LRF (subdistribution hazard ratio, 2.82; 95% CI, 1.47 to 5.42; P = .0019), independent of oral cavity primary site and TP53 mutation status. CONCLUSION: TERT promoter status is associated with the cumulative incidence of LRF and patterns of failure. TERT promoter mutations may define a subset of OSCCs with unique pathogenesis that is associated with an increased risk of LRF. Validation in prospective cohorts is warranted.


Assuntos
Carcinoma de Células Escamosas/genética , Neoplasias Bucais/genética , Recidiva Local de Neoplasia/genética , Telomerase/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Boca/patologia , Neoplasias Bucais/mortalidade , Neoplasias Bucais/patologia , Mutação , Papillomaviridae/genética , Regiões Promotoras Genéticas/genética , Estudos Retrospectivos , Análise de Sobrevida , Proteína Supressora de Tumor p53/genética
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