Evaluation of Tissue and Serum Expression Levels of Lactate Dehydrogenase Isoenzymes in Patients with Head and Neck Squamous Cell Carcinoma

Background: Head and Neck Squamous Cell Carcinoma (HNSCC) is a common malignancy that is associated with high morbidity and mortality all over the world. We explored the role of mRNA expression of both subunits of LDH in the early diagnosis of HNSCC. Materials and Methods: This was a case-control study on 62 healthy individuals and 62 patients with HNSCC. The expression of LDH in tumors and healthy tissue margins, and in the serum of both HNSCC patients and healthy individuals was evaluated using a quantitative real-time PCR method. Analysis of LDH-A and LDH-B expression and sensitivity-specificity analysis were carried out using SPSS software. Results: mRNA expression levels of LDH-A (4.18±1.29) and LDH-B (2.85±1.07) isoenzymes in tumor tissues were significantly higher than the expressions in the corresponding healthy tissue margins (1.85±0.56 and 1.61±0.56 for LDH-A and LDH-B, respectively). A comparison of LDH-B expression between histological grade I tumor tissue (2.74±0.19) and marginal tissue (1.62±0.90) showed a significant difference (P=0.016). Patients with a positive history of alcohol consumption and cigarette smoking had significantly higher mRNA expression of LDH-A (P=0.024) and LDH-B (P=0.03) in the marginal tissue and blood, respectively. The highest sensitivity and specificity values pertained to the mRNA expression of LDH-A (90.9%) and LDH-B (85.5%) in the blood. Conclusion: This is the first study reporting LDH gene expression as a biomarker in blood and tumoral tissue of HNSCC patients. Given the highest sensitivity and specificity values for LDH-A and LDH-B in blood, we recommend the simultaneous evaluation of both LDH isoenzymes in blood samples as a potential diagnostic method.

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Expression levels of miR-34-family microRNAs are associated with TP53 mutation status in head and neck squamous cell carcinoma

European Archives of Oto-Rhino-Laryngology ◽

10.1007/s00405-018-5223-x ◽

2018 ◽

Vol 276 (2) ◽

pp. 521-533 ◽

Cited By ~ 2

Author(s):

Chanatip Metheetrairut ◽

Chanticha Chotigavanich ◽

Kanchana Amornpichetkul ◽

Phawin Keskool ◽

Sunun Ongard ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Tp53 Mutation ◽

Neck Squamous Cell Carcinoma ◽

Mutation Status ◽

Expression Levels

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Immunohistochemical expression levels of p53 and eIF4E markers in histologically negative surgical margins, and their association with the clinical outcome of patients with head and neck squamous cell carcinoma

Molecular and Clinical Oncology ◽

10.3892/mco.2015.689 ◽

2015 ◽

Vol 4 (2) ◽

pp. 166-172 ◽

Cited By ~ 7

Author(s):

JAGTAR SINGH ◽

RAMA JAYARAJ ◽

SIDDHARTHA BAXI ◽

MARIANA MILEVA ◽

JOHN SKINNER ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Clinical Outcome ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Surgical Margins ◽

Neck Squamous Cell Carcinoma ◽

Immunohistochemical Expression ◽

Expression Levels

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Purine Metabolites in Tumor-Derived Exosomes May Facilitate Immune Escape of Head and Neck Squamous Cell Carcinoma

Cancers ◽

10.3390/cancers12061602 ◽

2020 ◽

Vol 12 (6) ◽

pp. 1602 ◽

Cited By ~ 3

Author(s):

Nils Ludwig ◽

Delbert G. Gillespie ◽

Torsten E. Reichert ◽

Edwin K. Jackson ◽

Theresa L. Whiteside

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Immune Escape ◽

Neck Squamous Cell Carcinoma ◽

Early Stage Disease ◽

Expression Levels ◽

Purine Metabolites ◽

Purine Metabolite

Body fluids of patients with head and neck squamous cell carcinoma (HNSCC) are enriched in exosomes that reflect properties of the tumor. The aim of this study was to determine whether purine metabolites are carried by exosomes and evaluate their role as potential contributors to tumor immune escape. The gene expression levels of the purine synthesis pathway were studied using the Cancer Genome Atlas (TCGA) Head and Neck Cancer database. Exosomes were isolated from supernatants of UMSCC47 cells and from the plasma of HNSCC patients (n = 26) or normal donors (NDs; n = 5) using size exclusion chromatography. Ultraperformance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) was used to assess levels of 19 purine metabolites carried by exosomes. In HNSCC tissues, expression levels of genes involved in the purinergic pathway were upregulated indicating an accelerated purine metabolism compared to normal tissues. Exosomes from supernatants of UMSCC47 cells contained several purine metabolites, predominantly adenosine and inosine. Purine metabolite levels were enriched in exosomes isolated from the plasma of HNSCC patients compared to those isolated from NDs and carried elevated levels of adenosine (p = 0.0223). Exosomes of patients with early-stage disease and no lymph node metastasis contained significantly elevated levels of adenosine and 5′-GMP (p = 0.0247 and p = 0.0229, respectively). The purine metabolite levels in exosomes decreased in patients with advanced cancer and nodal involvement. This report provides the first evidence that HNSCC cells shuttle purine metabolites in exosomes, with immunosuppressive adenosine being the most prominent purine. Changes in the content and levels of purine metabolites in circulating exosomes reflect disease progression in HNSCC patients.

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Predicting tumor mutational burden in head and neck squamous cell carcinoma based on CT imaging features: A TCGA/TCIA study.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e15254 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e15254-e15254

Author(s):

Yangkun Luo ◽

Lu Li ◽

Gang Yin ◽

Jin Yi Lang

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Sensitivity And Specificity ◽

Squamous Cell ◽

Texture Features ◽

Performance Estimation ◽

Neck Squamous Cell Carcinoma ◽

Imaging Features ◽

Mutation Burden

e15254 Background: Immunotherapy has substantially changed the therapeutic strategies for cancers. Unfortunately, only 20–50% of patients with advanced solid tumours respond to treatment. There is therefore a need for the development of methods to identify patients who are most likely to respond to immunotherapy. Tumor mutation burden (TMB) have been served as the most prevalent biomarkers to predict immunotherapy response. This study was designed to investigate the ability of radiomics to predict TMB status in patients with head and neck squamous cell carcinoma (HNSCC). Methods: TMB values were calculated using genomic data obtained from the HNSCC dataset in The Cancer Genome Atlas (TCGA).We identified matching patients (n = 100) who underwent contrast-enhanced CT scan prior to treatment from The Cancer Imaging Archive (TCIA),and patients were grouped based on the cutoff value; high group(>4.2 mutations/Mb) and low group(≤4.2 mutations/Mb). A total of 249 radiomics features(9 non-texture features and 240 scan-texture-parameter features) were extracted from CT images of the tumor. The incorporation of features into multivariable models was performed using logistic regression. The multivariable modeling strategy involved imbalance-adjusted bootstrap resampling in the following four steps leading to final prediction model construction: (1) feature set reduction; (2) feature selection; (3) prediction performance estimation; and (4) computation of model coefficients. The performance was evaluated in terms of area under the curve (AUC), sensitivity, and specificity. Results: Among all the features, twenty features were found to have the most impact on the predictive value; the two top texture parameters were GLCM-Variance and GLCM-Sum Average. In multivariable analysis, the best performance was obtained using a combination of seven texture features that can discriminate between high mutation burden versus low mutation burden. The AUC, sensitivity, and specificity of this model were 0.97 ± 0.01, 0.92 ± 0.04, and 0.92 ±0.01, respectively. Conclusions: The proposed CT-derived predictive model can accurately predict TMB status in patients with HNSCC. It may be helpful in guiding immunotherapy in clinical practice and deserves further analysis.

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