Tongue Cancer Patients Can be Distinguished from Healthy Controls by Specific <i>N</i>‐Glycopeptides Found in Serum

Saraswat, Mayank; Mäkitie, Antti; Tohmola, Tiialotta; Dickinson, Amy; Saraswat, Shruti; Joenväära, Sakari; Renkonen, Suvi

doi:10.1002/prca.201800061

Cited by 19 publications

(19 citation statements)

References 35 publications

(30 reference statements)

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“…However, the 3-year overall survival rate of Mroueh et al (24) from Finland who studied 360 patients was 80%.This may be attributed to | 107 the very high socioeconomic standard in Finland. The non-satisfactory survival rates of tongue cancer make identification of early serum markers for tumor detection, such as N-glycopeptides, urgent (25). Regarding the prognostic factors, age was not among our prognostic factors.…”

Section: Discussionmentioning

confidence: 79%

Squamous Cell Carcinoma of the Oral Tongue: A Single Institution Retrospective Cohort Study from Mansoura University Hospital

Hamdy

Halim

2019

Indonesian Journal of Cancer

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Background: Egyptian hospital–based statistics showed that head & neck carcinomas represent 18% of all cancers and mostly diagnosed at advanced stages. Our Clinical Oncology & Nuclear Medicine Department of Mansoura Faculty of Medicine serves a large rural area of the Delta region of Egypt. There is no previous study in our institution that focused on oral tongue carcinoma alone. This study aims in establishing the demographics, treatment outcome and prognostic factors of oral tongue squamous cell carcinoma (SCC).Methods: We retrospectively reviewed data of 50 cases with oral tongue SCC treated in our department from January 2014 to December 2016 to evaluate the demography, pathological characteristics, and therapeutic modalities. We estimated the survival rates during the entire follow-up period by the Kaplan–Meier method. The univariate and multivariate Cox proportional hazards analysis were performed for prognostic factors determination.Results: The median follow-up was 30 months (range: 4-45 months). The 3-year overall survival (OS) and disease-free survival (DFS) rates were 68% and 60% respectively. By univariate analysis, both advanced stages (III, IVA) and depth of invasion >0.5 cm were statistically significant as prognostic factors for 3-year DFS and OS rates. DFS rates were 34% vs. 98% for stage III and IVA vs. stage I and II respectively (p = 0.001); 52% vs. 78% for >0.5 cm vs. ≤0.5 cm depth of invasion (p = 0.003). OS rates were 36% vs. 99% for stage III and IVA vs. stage I and II respectively (p = 0.002); 52% vs. 80% for >0.5 cm vs. ≤0.5 cm depth of invasion (p = 0.001). Multivariate analysis of prognostic factors affecting 3-year DFS and OS rates confirmed the statistical significance of the same 2 factors.Conclusions: The majority of our patients were males below 60 years. Tumors were mainly found at stage III and were moderately differentiated. Vascular invasion and lymphatic permeation were uncommon. Staging and tumor invasion depth significantly affected the outcome. The 3-year OS and DFS were 68% and 60% respectively.

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Section: Discussionmentioning

confidence: 79%

Squamous Cell Carcinoma of the Oral Tongue: A Single Institution Retrospective Cohort Study from Mansoura University Hospital

Hamdy

Halim

2019

Indonesian Journal of Cancer

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“…38 Compared to healthy controls, oral squamous cell carcinoma patients have different expression levels of N-glycotypes of several serum proteins, such as Tf, IgG1, IgG4, and haptoglobin. 39 The serum profile of Tf isoforms is altered in patients with rheumatoid arthritis (RA) and RA patients treated with rituximab. Thus, we can predict that the levels of trisialylated isoforms of Tf Figure 1 The process of Tf binding to a receptor to transport iron.…”

Section: Non-enzymatic Glycated Modification Of Tf and Related Diseasesmentioning

confidence: 99%

Non-Enzymatic Glycation of Transferrin and Diabetes Mellitus

Ma¹,

Cai²,

Wang³

et al. 2021

DMSO

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Diabetes is a metabolic disease characterized by high blood sugar. Its complications may damage multiple organs, such as eyes, kidneys, heart, blood vessels, and nerves, severely threatening human health. Transferrin (Tf) is a major iron transport protein in the body. Recent studies have shown that the degree of non-enzymatic glycated modification of Tf is increased in diabetic patients, and glycated Tf is closely related to the occurrence and development of diabetes and diabetic complications. However, the molecular mechanisms underlying this glycated modification in diabetes and diabetic complications are still unclear. It is speculated that the mechanism may be that glycated modification reduces the binding ability of Tf and its receptor TfR, followed by excessive iron accumulation in the body. Iron overload in the body may further lead to the death of pancreatic beta cells and insulin resistance by increasing oxidative stress, inducing iron death, interfering with the insulin signaling pathway, and causing autophagy deficiency. In addition, non-enzymatic glycation affects the binding of Tf with chromium and reduces the ability of Tf to transport chromium into tissues, resulting in a decrease in the levels of chromium in tissues and ultimately affecting the sensitivity of tissues to insulin. In diabetic patients, the concentrations of glycated Tf in serum were significantly correlated with those of fructosamine.Tf has a shorter half-life, and not affected by anemia or hypoalbuminemia and less negative charge under physiological conditions, while glycated modification could not change the isoelectric point of Tf, which easily passes through the negatively charged basement membrane of the glomerulus. Therefore, compared to glucosamine, HbA1C, etc., glycated Tf may be a future biomarker for evaluating short-term glycemic control and early renal damage in diabetic patients.

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“…In a word, it is urgent to develop a panel of useful biomarkers for OSCC early diagnosis (10,11). However, metabolomics studies of OSCC are very limited up to date; many studies use serum and saliva samples (12,13), and there is lack of research on a specific metabolic type, such as amino acid metabolism. In this study, we aim to explore tissue-based amino acids metabolite biomarkers of OSCC by untargeted and targeted metabolomics, which not only distinguish cancer cell from normal tissues, but also used as prognostic methods for early detection of OSCC.…”

Section: Introductionmentioning

confidence: 99%

Integrated Non-targeted and Targeted Metabolomics Uncovers Amino Acid Markers of Oral Squamous Cell Carcinoma

et al. 2020

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Purpose: It is very important to develop potential molecular associated with oral squamous cell carcinoma (OSCC) malignant transformation and progression. Thus, the aim of our study was to determine the amino acid metabolic characteristics of OSCC patients and test their diagnostic value.Experimental Design: Eight pairs of matched tumor and normal samples were collected for gas chromatography-mass spectrometry (GC-MS) high-throughput untargeted analysis. Another 20 cases (each case including tumor and normal tissues) were also enrolled for ultrahigh-performance liquid chromatography-tandem mass spectrometer (UHPLC-MS/MS) amino acid quantitative analysis. T-test and receiver operating characteristic (ROC) curve analysis were used to determine candidate markers. Principal component analysis, partial least squares discriminant analysis, and heat map analysis were used to verify the ability of candidate markers to distinguish tumors from normal tissues.Results: A total of 10 amino acids biomarker were selected as OSCC candidate diagnostic biomarkers by GC-MS high-throughput untargeted metabolomics analyses [area under the curve (AUC) >0.80]. We further measured the specific concentration of these candidate amino acids biomarkers in another batch of 20 cases by UHPLC-MS/MS quantitative analysis. The result validated that nine amino acids had been detected, which had statistically significant difference (t-test, p < 0.05). Moreover, three of nine amino acid markers (glutamate, aspartic acid, and proline) displayed high sensitivity and specificity (AUC >0.90) by ROC curve analysis and obtained optimal sensitivity and specificity by binary logistic regression in the Glmnet package (AUC = 0.942). Conclusions:In conclusion, a panel including three amino acids (glutamate, aspartic acid, and proline) was identified as potential diagnostic biomarkers of OSCC by a combination of non-targeted and targeted metabolomics methods.

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Tongue Cancer Patients Can be Distinguished from Healthy Controls by Specific N‐Glycopeptides Found in Serum

Abstract: The authors are the first to suggest specific N-glycopeptides to serve as potential serum biomarkers to detect preclinical OSCC in patients. These N-glycopeptides are the lead candidates for validation as future diagnostic modalities of OSCC as early as stage I.

Cited by 19 publications

References 35 publications

Squamous Cell Carcinoma of the Oral Tongue: A Single Institution Retrospective Cohort Study from Mansoura University Hospital

Squamous Cell Carcinoma of the Oral Tongue: A Single Institution Retrospective Cohort Study from Mansoura University Hospital

Non-Enzymatic Glycation of Transferrin and Diabetes Mellitus

Integrated Non-targeted and Targeted Metabolomics Uncovers Amino Acid Markers of Oral Squamous Cell Carcinoma

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