scholarly journals Overexpression of eIF3a in Squamous Cell Carcinoma of the Oral Cavity and Its Putative Relation to Chemotherapy Response

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Rita Spilka ◽  
Klaus Laimer ◽  
Felix Bachmann ◽  
Gilbert Spizzo ◽  
Alexander Vogetseder ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Cavity ◽  
Tumor Marker ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Translation Initiation ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Study Cohort ◽  
Platinum Based Chemotherapy

The eukaryotic translation initiation factor eIF3a is one of the core subunits of the translation initiation complex eIF3, responsible for ribosomal subunit joining and mRNA recruitment to the ribosome. It is known to play an important role in general translation initiation as well as in the specific translational regulation of various gene products, among which many influence tumour development, progression, and the therapeutically important pathways of DNA damage repair. Therefore, beyond its role in protein synthesis, eIF3a is emerging as regulator in tumour pathogenesis and therapy response and, therefore, a potential tumor marker. By means of a tissue microarray (TMA) for histopathological and statistical assessment, we here show eIF3a expression in 103 cases of squamous cell carcinoma of the oral cavity (OSCC), representing tissues from 103 independent patients. A subset of the study cohort was treated with platinum based therapy. Our results show that the 170 kDa protein is upregulated in OSCC and correlates with good overall survival. Overexpressing tumors respond better to platinum-based chemotherapy, suggesting eIF3a as a putative predictive as well as prognostic tumor marker in OSCC.

scholarly journals N6-Methyladenosine Methyltransferase METTL14-Mediated Autophagy in Malignant Development of Oral Squamous Cell Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Fang Wang ◽  
Yue Zhu ◽  
Hongshi Cai ◽  
Jianfeng Liang ◽  
Wenjin Wang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Luciferase Reporter ◽  
Clinical Samples ◽  
Translation Efficiency ◽  
Rna Methylation

N6-methyladenosine (m6A) is the most abundant internal mRNA modification in eukaryotes and is related to stability, localization, or translation efficiency in tumorigenesis. Autophagy plays an important role in the occurrence and development of tumours. However, the relationship between m6A and autophagy remains unclear. In this study, we used a rapamycin-induced autophagy model of oral squamous cell carcinoma (OSCC) cells, and observed increased m6A RNA methylation. When autophagy was activated, the methyltransferase-like 14 (METTL14) expression was upregulated and influenced the proliferation, migration, and invasiveness of OSCC cells. Through meRIP-seq and RNA-seq analysis, we found that METTL14 directly combined with eukaryotic translation initiation factor gamma 1 (eIF4G1) mRNA and decreased its RNA stability. According to the dual-luciferase reporter and mutagenesis assay, the mutated site 1 of exon 11 of eIF4G1 is the key target of METTL14. Knockdown of the main m6A binding protein YTHDF2 may rescue the shortened half-life of eIF4G1 mRNA induced by METTL14 overexpression. Furthermore, an in vivo tumour xenograft model confirmed that a high METTL14 expression can effectively reduce OSCC growth. Additionally, using clinical samples, we found that patients with advanced or moderately/poorly differentiated tumours exhibited lower METTL14 levels. Taken together, our results revealed that METTL14 mediated eIF4G1 expression via m6A modification and regulated autophagy levels and biological functions in OSCC. Our findings not only expand our understanding of the correlation between autophagy and RNA methylation in tumorigenesis but also present an opportunity to develop new therapeutic options.

scholarly journals Dysregulated Protein Translation Control in Hidradenitis Suppurativa: Implication for Lesion-associated Squamous Cell Carcinoma Development

2021 ◽  
Author(s):  
Lin Jin ◽  
Mahendra P Kashyap ◽  
Yunjia Chen ◽  
Yuanyuan Guo ◽  
Jasim Khan ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cyclin D1 ◽  
Squamous Cell ◽  
Hidradenitis Suppurativa ◽  
Protein Translation ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Pathway Enrichment Analysis ◽  
Translation Control

Hidradenitis Suppurativa (HS) is a proinflammatory painful skin disorder. This chronic disease is often associated with aggressive squamous cell carcinoma (SCC). The molecular pathogenesis of this disease progression remains undefined. The translation initiation factor eIF4E/4G/4A1 complex is overexpressed in a variety of human malignancies. In this study, we found that the expression of eIF4E/4G/4A1 as well as phosphorylated eIF4E were upregulated in HS skin. In the global transcription profiles derived from two public database, we were able to enrich 734 eIF4F-related genes. GSEA pathway enrichment analysis further demonstrated that RAS/MEK/ERK oncogene signaling pathway associated with inflammation signaling were significantly activated in HS lesion. The increase expression of eIF4 protein components was associated with enhanced eIF4E translation targets Cyclin D1 and c-Myc. Confocal fluorescence microscopy analysis further revealed that Cyclin D1 and c-Myc specifically co-localized in nuclei of certain cells in HS epithelium. We also found that many of the PCNA positive hyperproliferative cells were also positive for c-Myc expression. These data demonstrate that 5-cap-dependent translation is a potential pathway underlying the SCC pathogenesis in chronic HS lesions. Furthermore, being a druggable target, inhibition of eIF4F may block lesion-associated lethal SCCs in HS patients.

Spindle Cell Carcinoma of the Tongue: Fallacies in Its Diagnosis

2018 ◽  
Vol 3 (02) ◽  
Author(s):  
Amrit Kaur Kaler, Shweta C, Smitha Chandra B.C, Rajeev Naik
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Cavity ◽  
Cell Carcinoma ◽  
Cell Population ◽  
Squamous Cell ◽  
Spindle Cell ◽  
Spindle Cell Carcinoma ◽  
Biphasic Tumor ◽  
Carcinoma Of The Tongue ◽  
Ihc Markers

Spindle cell carcinoma is a rare aggressive biphasic tumor, composed of neoplastic proliferation of both epithelial (squamous) and spindle cell population. It constitutes about 1% of all oral cavity tumors 2a and is almost rare on the tongue; only few cases have been reported so far. This variant of squamous cell carcinoma, comprises major diagnostic problems due to its varied histomorphology and resemblance to sarcomatous lesion; hence diligent screening and IHC markers are mandatory for its diagnosis.

PD-L1 and survival in oral cavity squamous cell carcinoma

2020 ◽  
Vol 25 (4) ◽  
pp. 287-294
Author(s):  
S. I. Kutukova ◽  
N. P. Beliak ◽  
G. A. Raskin ◽  
M. S. Mukhina ◽  
Yu. V. Ivaskova ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Cavity ◽  
Cell Carcinoma ◽  
Tumor Cells ◽  
Squamous Cell ◽  
Immune Cells ◽  
Negative Impact ◽  
Progression Free Survival ◽  
Negative Effect ◽  
Effect Of Pd

Relevance. Prognostic value of PD-L1 expression in oral cavity squamous cell carcinoma (OCSCC) and its effect on survival is still controversial. It should be to determine the prognostic role of PD-L1 expression on tumor and immune cells of OCSCC and assess their effect on overall survival (OS) and progression-free survival (PFS).Materials and methods. A prospective study included 145 patients, first diagnosed with OCSCC. PD-L1 expression on tumor and immune cells, infiltrating tumor and its microenvironment, was assessed in all tumor samples by IHC, CPS was calculated. Cut-off values were determined by ROC analysis for identification of PD-L1 expression effect on OS and PFS.Results. Most patients with oral mucosa squamous cell carcinoma showed positive expression of PD-L1 on tumor (77.2%) and immune cells (92.4%). The median PD-L1 expression on tumor cells was 13.5% [1.0-40.0], the median PD-L1 expression on immune cells was 5.0% [1.0-11.0], and the median CPS – 18.0 [3.0-7.8]. Univariate and multivariate analyses revealed a significant negative effect of PD-L1 expression on immune cells ≤ 7% on OS (HR 0.66; 95% CI 0.45-0.93; p = 0.0498); PD-L1 expression in tumor cells ≤ 15% (HR 0.65; 95% CI 0.43-0.98; p = 0.0416) and CPS ≤ 21 (HR 0.62; 95% CI 0.44-0.92; p = 0.0183) for PFS. PD-L1 expression in tumor cells ≤ 6% (HR 0.71; 95% CI 0.47-1.08; p = 0.1096) and CPS ≤ 7 (RR 0.67; 95% CI 0.44-1.01; p = 0.0575) had a confident tendency to negative impact on OS.Conclusion. Positive PD-L1 expression in tumor and immune cells as well as CPS are effective additional factors in the prognosis of the disease course, OS and PFS in patients with OCSCC.

The Length of Peri-Neural Spreading in Clinically Mandibular Invaded Oral Cavity Squamous Cell Carcinoma

2020 ◽  
pp. 459-464
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Cavity ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Lymphovascular Invasion ◽  
Perineural Invasion ◽  
Inferior Alveolar Nerve ◽  
Surgical Margin ◽  
Neural Invasion ◽  
Resected Margin

Background: The objective of surgical management of oral squamous cell carcinoma (OSCC) is adequate resection with a clear margin. However, there is still a debate as to the optimal length for a mandibular resected margin. Objective: To examine the length of peri-neural spreading in T4 mandibular invaded oral cavity squamous cell carcinoma. Materials and Methods: Twenty-eight T4 pathological OSCC specimens that involved mandible and serial slices were studied and the length of tumor spreading along the inferior alveolar nerve (IAN) was determined. Tumor characteristics, risk factors, and survival were analyzed. Results: The incidence of peri-neural invasion was 11.11%, and IAN invasion was found in 14.29% of the tumor-invaded mandibular marrow. The length of tumor spreading along IAN was 3 to 12 mm. Poor prognostic factors of T4 OSCC were it being located on the tongue (HR 14.16), was pathological N2-3 (HR 31.05), and had high-risk features such as peri-neural invasion, lymphovascular invasion, and extra-nodal extension. Conclusion: A mandibular resected margin of at least 18 mm is recommended as a clear surgical margin in cases of T4 mandibular invasion OSCC. Keywords: Oral cancer, Perineural invasion, Inferior alveolar nerve, Squamous cell carcinoma, Mandibulectomy

Sign in / Sign up

Export Citation Format

Share Document