scholarly journals Pre-Therapeutic VEGF Level in Plasma Is a Prognostic Bio-Marker in Head and Neck Squamous Cell Carcinoma (HNSCC)

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3781
Author(s):  
Julia Siemert ◽  
Theresa Wald ◽  
Marlen Kolb ◽  
Isolde Pettinella ◽  
Ulrike Böhm ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Cox Regression ◽  
Neck Squamous Cell Carcinoma ◽  
Operating Characteristics ◽  
Event Free Survival ◽  
Free Survival ◽  
Study Protocols

Vascular endothelial growth factor (VEGF) is centrally involved in cancer angiogenesis. We hypothesized that pre-therapeutic VEGF levels in serum and plasma differ in their potential as biomarkers for outcomes in head and neck squamous cell carcinoma (HNSCC) patients. As prospectively defined in the study protocols of TRANSCAN-DietINT and NICEI-CIH, we measured VEGF in pretreatment serum and plasma of 75 HNSCC test cohort (TC) patients. We analyzed the prognostic value of VEGF concentrations in serum (VEGFSerum) and plasma (VEGFPlasma) for event-free survival (EFS) utilizing receiver-operating characteristics (ROC). Mean VEGF concentrations in plasma (34.6, 95% CI 26.0–43.3 ng/L) were significantly lower (p = 3.35 × 10−18) than in serum (214.8, 95% CI 179.6–250.0 ng/L) but, based on ROC (area under the curve, AUCPlasma = 0.707, 95% CI 0.573–0.840; p = 0.006 versus AUCSerum = 0.665, 95% CI 0.528–0.801; p = 0.030), superiorly correlated with event-free survival (EFS) of TC patients. Youden indices revealed optimum binary classification with VEGFPlasma 26 ng/L and VEGFSerum 264 ng/L. Kaplan–Meier plots demonstrated superiority of VEGFPlasma in discriminating patients regarding outcome. Patients with VEGFPlasma < 26 ng/L had superior nodal (NC), local (LC) and loco-regional control (LRC) leading to significant prolonged progression-free survival (PFS) and EFS. We successfully validated VEGFPlasma according the cut-off <26 ng/L as predictive for superior outcome in an independent validation cohort (iVC) of 104 HNSCC patients from the studies DeLOS-II and LIFE and found better outcomes including prolonged tumor-specific (TSS) and overall survival (OS). Outcomes in TC and iVC combined again was related to VEGFPlasma, and multivariate Cox regression revealed that VEGFPlasma was an independent outcome predictor. In HNSCC, pre-therapeutic VEGFPlasma is prognostic for outcomes.

scholarly journals Prognostic Biomarkers of Salvage Chemotherapy Following Nivolumab Treatment for Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2299 ◽  
Author(s):  
Takahiro Wakasaki ◽  
Ryuji Yasumatsu ◽  
Muneyuki Masuda ◽  
Toranoshin Takeuchi ◽  
Tomomi Manako ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Progression Free Survival ◽  
Salvage Chemotherapy ◽  
Neck Squamous Cell Carcinoma ◽  
Prognostic Biomarkers ◽  
Free Survival ◽  
Reactive Protein

Recent studies have suggested the benefit of salvage chemotherapy (SCT) after immune checkpoint inhibitor (ICI) treatment for recurrent and metastatic head and neck squamous cell carcinoma (R/M HNSCC). We retrospectively examined the outcome of SCT and the usefulness of the serum C-reactive protein level (CRP) and neutrophil-to-lymphocyte ratio (NLR) as prognostic biomarkers. Thirty-nine patients with R/M HNSCC were enrolled in this study. Twenty-five patients (64.1%) received combination chemotherapy of weekly paclitaxel and cetuximab (PC) as SCT, and 14 patients (35.9%) received tegafur-gimestat-otastat potassium (S1), an oral fluoropyrimidine. In all patients, the response rate, disease control rate, median progression-free survival (PFS), and median overall survival (OS) were 45.2%, 85.7%, 6.5 months, and 13.5 months, respectively. No chemotherapy-related deaths were observed. These PC groups had low CRP (<1.2 mg/dL) or low NLR (<7.0) values at the time of SCT induction, which was significantly associated with an improved OS (p = 0.0440, p = 0.0354). A multivariate analysis also showed that a lower CRP value was significantly associated with a better OS (p = 0.0078). We clarified the usefulness of the PC and S1 regimens as SCT. In addition, SCT with the PC regimen showed a better prognosis with a lower CRP or NLR at induction than a higher CRP or NLR. This is the first report on biomarkers of SCT in R/M HNSCC.

scholarly journals Predictors of Survival After Head and Neck Squamous Cell Carcinoma in South America: The InterCHANGE Study

2020 ◽  
pp. 486-499 ◽  
Author(s):  
Renata Abrahão ◽  
Sandra Perdomo ◽  
Luis Felipe Ribeiro Pinto ◽  
Flávia Nascimento de Carvalho ◽  
Fernando Luis Dias ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
South America ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Cox Regression ◽  
Survival Rates ◽  
Stage Iv ◽  
Neck Squamous Cell Carcinoma ◽  
Stage Iv Disease

PURPOSE Head and neck squamous cell carcinoma (HNSCC) incidence is high in South America, where recent data on survival are sparse. We investigated the main predictors of HNSCC survival in Brazil, Argentina, Uruguay, and Colombia. METHODS Sociodemographic and lifestyle information was obtained from standardized interviews, and clinicopathologic data were extracted from medical records and pathologic reports. The Kaplan-Meier method and Cox regression were used for statistical analyses. RESULTS Of 1,463 patients, 378 had a larynx cancer (LC), 78 hypopharynx cancer (HC), 599 oral cavity cancer (OC), and 408 oropharynx cancer (OPC). Most patients (55.5%) were diagnosed with stage IV disease, ranging from 47.6% for LC to 70.8% for OPC. Three-year survival rates were 56.0% for LC, 54.7% for OC, 48.0% for OPC, and 37.8% for HC. In multivariable models, patients with stage IV disease had approximately 7.6 (LC/HC), 11.7 (OC), and 3.5 (OPC) times higher mortality than patients with stage I disease. Current and former drinkers with LC or HC had approximately 2 times higher mortality than never-drinkers. In addition, older age at diagnosis was independently associated with worse survival for all sites. In a subset analysis of 198 patients with OPC with available human papillomavirus (HPV) type 16 data, those with HPV-unrelated OPC had a significantly worse 3-year survival compared with those with HPV-related OPC (44.6% v 75.6%, respectively), corresponding to a 3.4 times higher mortality. CONCLUSION Late stage at diagnosis was the strongest predictor of lower HNSCC survival. Early cancer detection and reduction of harmful alcohol use are fundamental to decrease the high burden of HNSCC in South America.

scholarly journals Association of Genetic Variants in ANGPT/TEK and VEGF/VEGFR with Progression and Survival in Head and Neck Squamous Cell Carcinoma Treated with Radiotherapy or Radiochemotherapy

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1506
Author(s):  
Dorota Butkiewicz ◽  
Agnieszka Gdowicz-Kłosok ◽  
Małgorzata Krześniak ◽  
Tomasz Rutkowski ◽  
Aleksandra Krzywon ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Neck Squamous Cell Carcinoma ◽  
Vegf Receptor ◽  
Recurrence Free Survival ◽  
Nucleotide Polymorphisms ◽  
Multiple Testing Correction ◽  
Free Survival

Angiogenesis is essential for growth, progression, and metastasis of solid tumors. Vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) and angiopoietin (ANGPT)/ tyrosine kinase endothelial (TEK) signaling plays an important role in regulating angiogenesis. Very little is known about the effects of single-nucleotide polymorphisms (SNPs) in angiogenesis-related genes on treatment outcome in head and neck squamous cell carcinoma (HNSCC). Therefore, we evaluated the association between SNPs in ANGPT1, ANGPT2, TEK, VEGF, VEGFR1, and VEGFR2 genes and five clinical endpoints in 422 HNSCC patients receiving radiotherapy alone or combined with chemotherapy. Multivariate analysis showed an association of ANGPT2 rs3739391, rs3020221 and TEK rs639225 with overall survival, and VEGF rs2010963 with overall and metastasis-free survival. VEGFR2 rs1870377 and VEGF rs699947 affected local recurrence-free survival in all patients. In the combination treatment subgroup, rs699947 predicted local, nodal, and loco-regional recurrence-free survival, whereas VEGFR2 rs2071559 showed an association with nodal recurrence-free survival. However, these associations were not statistically significant after multiple testing correction. Moreover, a strong cumulative effect of SNPs was observed that survived this adjustment. These SNPs and their combinations were independent risk factors for specific endpoints. Our data suggest that certain germline variants in ANGPT2/TEK and VEGF/VEGFR2 axes may have predictive and prognostic potential in HNSCC treated with radiation or chemoradiation.

scholarly journals Data Mining Identifies Six Proteins that Can Act as Prognostic Markers for Head and Neck Squamous Cell Carcinoma

2020 ◽  
Vol 29 ◽  
pp. 096368972092930
Author(s):  
Zeng-hong Wu ◽  
Yun-Tang ◽  
Qing Cheng
Keyword(s):  
Squamous Cell Carcinoma ◽  
Regression Analysis ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
High Throughput Sequencing ◽  
Cox Regression ◽  
Neck Squamous Cell Carcinoma ◽  
The Cancer Genome Atlas ◽  
Cox Regression Analysis

Head and neck squamous cell carcinoma (HNSCC) is a malignant tumor of the upper aerodigestive tract affecting the oral cavity, lips, paranasal sinuses, larynx, and nasopharynx. Proteogenomics combines proteomics and genomics and employs mass spectrometry and high-throughput sequencing technologies to identify novel peptides. The aim of this study was to identify potential protein biomarkers for clinical treatment of HNSCC. To achieve this, we utilized two sets of data, one on proteins from The Cancer Proteome Atlas (TCPA) and the other on gene expression from The Cancer Genome Atlas (TCGA) database, to evaluate dysfunctional proteogenomics microenvironment. Univariate Cox regression analysis was performed to examine the relationship between protein signatures and prognosis. A total of 19 proteins were significantly associated with overall survival (OS) of patients, of which E2F transcription factor 1 (E2F1; HR = 4.557, 95% CI = 1.810 to 11.469) and enhancer of zeste homolog 2 (EZH2; HR = 0.430, 95% CI = 0.187 to 0.984) were the most differentially expressed between patients with longer and shorter OS, respectively. Furthermore, multivariate Cox regression analysis on six proteins (ERALPHA, HER3, BRAF, P27, RAPTOR, and E2F1) was performed to build the prognostic model. The receiver operating characteristic curves were used to determine whether the expression pattern of survival-related proteins could provide an early prediction of the occurrence of HNSCC. Herein, we found an AUC of 0.720. Based on an online database, we identified novel protein markers for the prognosis of HNSCC. The findings of the present study may provide new insights into the development of new and reliable tools for precise cancer intervention.

HLA traits linked to development of head and neck squamous cell carcinoma affect the progression-free survival of patients

Oral Oncology ◽  
2017 ◽  
Vol 69 ◽  
pp. 115-127 ◽  
Author(s):  
Gunnar Wichmann ◽  
Cindy Herchenhahn ◽  
Andreas Boehm ◽  
Christian Mozet ◽  
Mathias Hofer ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Progression Free Survival ◽  
Neck Squamous Cell Carcinoma ◽  
Free Survival

scholarly journals Six Glycolysis-Related Genes as Prognostic Risk Markers Can Predict the Prognosis of Patients with Head and Neck Squamous Cell Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
LangXiong Chen ◽  
XiaoSong He ◽  
ShiJiang Yi ◽  
GuanCheng Liu ◽  
Yi Liu ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Regression Analysis ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Cox Regression ◽  
Neck Squamous Cell Carcinoma ◽  
Risk Markers ◽  
Cox Regression Analysis ◽  
Normal Head

Objective. Head and neck squamous cell carcinoma (HNSCC) is one of the worst-prognosis malignant tumors. This study used bioinformatic analysis of the transcriptome sequencing data of HNSCC and the patients’ survival and clinical data to construct a prediction signature of glycolysis-related genes as the prognostic risk markers. Methods. Gene expression profile data about HNSCC tissues ( n = 498 ) and normal tissues in the head and neck ( n = 44 ) were got from The Cancer Genome Atlas (TCGA), as well as patients’ survival and clinical data. Then, we obtained core genes; their expression in head and neck squamous cell carcinoma tissues is significantly different from that in normal head and neck tissues. The predicted glycolysis-related genes are screened through univariate Cox regression analysis, and then, the prognostic risk markers were constructed through further correction of multivariate Cox regression analysis. The Kaplan-Meier curve and receiver operating characteristic curve are used to analyze the potential value of these risk markers in diagnosis and prognosis. We also evaluated that the glycolysis-related prognostic risk markers composed of 6 oncogenes are correlated with clinical features, such as age, gender, grade, and clinical stage of the tumor, by univariate and multivariate Cox regression analyses. Results. Differentially expressed glycolytic genes in HNSCC tissues and normal head and neck tissues were screened from TCGA databases using the bioinformatic method. We confirmed a set of six glycolytic genes that were significantly associated with OS in the test series. According to our analysis, the prognostic risk markers composed of HPRT1, STC2, PLCB3, GPR87, PYGL, and SLC5A12 may be an independent risk factor for the prognosis of HNSCC. Conclusions. Through this analysis, we constructed new prognostic risk markers related to glycolysis as a prognostic risk marker for patients with HNSCC and provided new ideas and molecular targets for the research and individualized treatment of HNSCC.

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