scholarly journals Methylene tetrahydrofolate dehydrogenase 2 (MTHFD2) is overexpressed in head and neck squamous cell carcinoma (HNSCC) and correlated with patient’s poor prognosis

Pteridines ◽  
2021 ◽  
Vol 32 (1) ◽  
pp. 98-105
Author(s):  
Biqiang Sun ◽  
Zhijun He ◽  
Gan Liu ◽  
Xiao Fu ◽  
Zhiyong Chen ◽  
...  

Abstract Objective To investigate methylene tetrahydrofolate dehydrogenase 2 (MTHFD2) expression, biological function, and correlation with head and neck squamous cell carcinoma (HNSCC) patient’s prognosis. Methods The relative expression levels of MTHFD2 gene mRNA in tumor tissues of HNSCC and adjacent normal tissues were analyzed in the Cancer Genome Atlas and oncomine database. MTHFD2 protein relative expression in tumor tissue of HNSCC patients was analyzed in human proteome database. Protein–protein interaction (PPI) network of MTHFD2 and correlated genes were constructed in STRING database. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway of MTHFD2 and relevant proteins involved in the PPI network was enriched. The Tumor Immune Estimation Resource database was used to analyze the relationship between MTHFD2 expression and immune infiltration. Overall survival (OS) and progression-free survival (PFS) for MTHFD2 high and low expression groups were investigated in the Kaplan–Meier Plotter database. Results In HNSCC, MTHFD2 mRNA relative expression level in tumor tissue was significantly higher than the corresponding normal tissue with statistical difference (p < 0.05). In the PPI network, 21 protein coding genes were involved in the network with 124 edges, which indicated that the enrichment was significant (p < 0.05). MTHFD2 and PPI network involved genes were mainly enriched in tetrahydrofolate metabolic process, one-carbon metabolic process biological process. In KEGG pathway, MTHFD2 and PPI network involved genes were mainly enriched in one-carbon pool by folate, metabolic pathways, glyoxylate, and dicarboxylate metabolism, and carbon metabolism. The relative expression level of MTHFD2 gene was correlated with immune infiltration of macrophage (r = 0.712, p < 0.05), neutrophil (r = 0.158, p < 0.05), dendritic cell (r = 0.1825, p < 0.05), and CD4+ T lymph cell (r = 0.1825, p < 0.05). HNSCC patients with high expression MTHFD2 had low OS compared to low expression cases (hazard ratio = 1.53, 95% CI: 1.16–2.02, p < 0.05). Conclusion MTHFD2 is overexpressed in HNSCC and correlated with patient’s prognosis. MTHFD2 maybe a potential target for HNSCC target treatment and provides a possible direction for the research and development of related targeted drugs.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e13578-e13578
Author(s):  
Helene Roussel ◽  
Martin Housset ◽  
Helene Tournat ◽  
Patrice Ravel ◽  
Stephane Hans ◽  
...  

e13578 Background: Head and neck squamous cell carcinoma (HNSCC) treatment had undergone important changes, in particular due to the organ preservation and the advent of chemotherapy, particularly using platinum. The excision repair cross-complementation group 1 (ERCC1) enzyme plays a rate-limiting role in the nucleotide excision repair pathway and has been associated with resistance to platinum-based chemotherapy. The purpose of this study was to evaluate the role of ERCC1expression with p16 and Ki-67 as predictive markers in the response to platin-based induction chemotherapy and as prognostic markers in patients with HNSCC. Methods: 208 patients treated from 2000 to 2006 by an induction chemotherapy regimen for HNSCC were included retrospectively. ERCC1 (8F1 and FL297 clone), p16 and Ki-67 staining were performed on paraffin-embedded tumor tissue collected before chemotherapy. We assessed response to treatment, progression-free survival (PFS) and overall survival (OS). Results: Respectively, 68% (142/208 patients) and 81.5% (163/200 patients) of HNSCC showed low expression of 8F1 and FL297 ERCC1. No correlation was found between the two clones (p=0.1). There was no correlation between the expression of 8F1 ERCC1, FL297 ERCC1 and Ki-67 and the response to induction chemotherapy, OS or PFS. However, in the subgroup of 129 patients treated with induction cisplatin-5FU chemotherapy, a low expression of 8F1 ERCC1 was significantly associated with a better response (p=0.027). Over expression of p16, found in 34.5% of cancers of the oropharynx was significantly correlated with a better OS (p=0.0007) and a better PFS (p = 0.01). Conclusions: These results suggest that ERCC1 expression might be a useful predictive marker of HNSCC in patients treated by cisplatin-based chemotherapy. The 8F1 ERCC1 clone appears to be the best for immunohistochemical analysis; clone FL297 did not show any association with treatment response and survival. Independently, our study confirms the prognostic value of the over expression of p16 in carcinoma of the oropharynx.







Author(s):  
Marina Marques Toledo ◽  
Bruno De Souza Gonçalves ◽  
Natalie Mounteer Colodette ◽  
Aline Lauda Freitas Chaves ◽  
Luciana Vieira Muniz ◽  
...  


2013 ◽  
Vol 21 (5) ◽  
pp. 416-421 ◽  
Author(s):  
Camila Santos Pereira ◽  
Marcos Vinicius Macedo de Oliveira ◽  
Lucas Oliveira Barros ◽  
Gabriela Alencar Bandeira ◽  
Sergio Henrique Sousa Santos ◽  
...  


Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 3980
Author(s):  
Igor Piotrowski ◽  
Xiang Zhu ◽  
Tatiana Dandolini Saccon ◽  
Sarah Ashiqueali ◽  
Augusto Schneider ◽  
...  

Head and Neck Squamous Cell Carcinoma (HNSCC) is the sixth most common cancer worldwide. These tumors originate from epithelial cells of the upper aerodigestive tract. HNSCC tumors in different regions can have significantly different molecular characteristics. While many microRNAs (miRNAs) have been found to be involved in the regulation of the carcinogenesis and pathogenesis of HNSCC, new HNSCC related miRNAs are still being discovered. The aim of this study was to explore potential miRNA biomarkers that can be used to diagnose HNSCC and prognose survival of HNSCC patients. For this purpose, we chose a panel of 12 miRNAs: miR-146a-5p, miR-449a, miR-126-5p, miR-34a-5p, miR-34b-5p, miR-34c-5p, miR-217-5p, miR-378c, miR-6510-3p, miR-96-5p, miR-149-5p, and miR-133a-5p. Expression of these miRNAs was measured in tumor tissue and neighboring healthy tissue collected from patients diagnosed with HNSCC (n = 79) in either the oral cavity, oropharynx, or larynx. We observed a pattern of differentially expressed miRNAs at each of these cancer locations. Our study showed that some of these miRNAs, separately or in combination, could serve as biomarkers distinguishing between healthy and tumor tissue, and their expression correlated with patients’ overall survival.



Oral Oncology ◽  
2003 ◽  
Vol 39 (1) ◽  
pp. 56-63 ◽  
Author(s):  
H Mineta ◽  
Ka Miura ◽  
S Takebayashi ◽  
Ki Misawa ◽  
Y Ueda ◽  
...  


PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e10385
Author(s):  
Yang Li ◽  
Ji-Na Zheng ◽  
En-Hao Wang ◽  
Chan-Juan Gong ◽  
Keng-Fu Lan ◽  
...  

Background Increasing evidence has shown that N6-methyladenosine (m6A) RNA methylation regulators have important biological functions in human cancers. However, there are few studies on the value of m6A reader protein YTHDC2 in the diagnosis and tumor-infiltrating of head and neck squamous cell carcinoma (HNSCC). Therefore, it is important to understand the potential clinical value of YTHDC2 in the prognosis and immune infiltration of HNSCC. Methods In this study, gene expression profiles and the corresponding clinical information of 270 HNSCC patients were downloaded from the Gene Expression Omnibus (GEO) database. The gene co-expression network was established to verify whether YTHDC2 was related to the prognosis of HNSCC and verified again in the public database. The correlations between YTHDC2 and immune infiltration was investigated via Tumor Immune Estimation Resource (TIMER) and Gene Expression Profiling Interactive Analysis (GEPIA). Results The results showed that YTHDC2 appeared in the blue module related to survival time and survival state and had a close correlation with the prognosis and immune infiltration level of HNSCC in public database. Patients with low expression of YTHDC2 had poor overall survival (OS) and recurrence-free survival (RFS) than those with high expression. In addition, the expression of YTHDC2 was positively correlated with the level of CD4+ T cell subpopulations infiltration in HNSCC. Conclusions Through this study, we found that YTHDC2 is a tumor suppressor gene with high expression in normal tissues and low expression in tumor tissues. In addition, YTHDC2 is correlated with the immune infiltrating levels of B cells, CD8+ T cells, CD4+ T cells, neutrophils, and dendritic cells in HNSCC, which may become a potential marker for prognosis and immune infiltration of HNSCC.



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