High expression of S100A4 and endoglin is associated with metastatic disease in head and neck squamous cell carcinoma

2014 ◽  
Vol 31 (6) ◽  
pp. 639-649 ◽  
Author(s):  
Marcos Vinícius Macedo de Oliveira ◽  
Carlos Alberto de Carvalho Fraga ◽  
Lucas Oliveira Barros ◽  
Camila Santos Pereira ◽  
Sérgio Henrique Sousa Santos ◽  
...  
Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1281 ◽  
Author(s):  
Kacper Guglas ◽  
Tomasz Kolenda ◽  
Maciej Stasiak ◽  
Magda Kopczyńska ◽  
Anna Teresiak ◽  
...  

YRNAs are a class of non-coding RNAs that are components of the Ro60 ribonucleoprotein particle and are essential for initiation of DNA replication. Ro60 ribonucleoprotein particle is a target of autoimmune antibodies in patients suffering from systemic lupus erythematosus and Sjögren’s syndrome. Deregulation of YRNAs has been confirmed in many cancer types, but not in head and neck squamous cell carcinoma (HNSCC). The main aim of this study was to determine the biological role of YRNAs in HNSCC, the expression of YRNAs, and their usefulness as potential HNSCC biomarkers. Using quantitative reverse transcriptase (qRT)-PCR, the expression of YRNAs was measured in HNSCC cell lines, 20 matched cancer tissues, and 70 FFPETs (Formaline-Fixed Paraffin-Embedded Tissue) from HNSCC patients. Using TCGA (The Cancer Genome Atlas) data, an analysis of the expression levels of selected genes, and clinical-pathological parameters was performed. The expression of low and high YRNA1 expressed groups were analysed using gene set enrichment analysis (GSEA). YRNA1 and YRNA5 are significantly downregulated in HNSCC cell lines. YRNA1 was found to be significantly downregulated in patients’ tumour sample. YRNAs were significantly upregulated in T4 stage. YRNA1 showed the highest sensitivity, allowing to distinguish healthy from cancer tissue. An analysis of TCGA data revealed that expression of YRNA1 was significantly altered in the human papilloma virus (HPV) infection status. Patients with medium or high expression of YRNA1 showed better survival outcomes. It was noted that genes correlated with YRNA1 were associated with various processes occurring during cancerogenesis. The GSEA analysis showed high expression enrichment in eight vital processes for cancer development. YRNA1 influence patients’ survival and could be used as an HNSCC biomarker. YRNA1 seems to be a good potential biomarker for HNSCC, however, more studies must be performed and these observations should be verified using an in vitro model.


2021 ◽  
Vol 10 ◽  
Author(s):  
Gang Chen ◽  
Zhexuan Li ◽  
Changhan Chen ◽  
Jiajia Liu ◽  
Weiming Zhu ◽  
...  

PRAS40 (Prolin-rich Akt substrate of 40 kDa) is a critical protein, which directly connects PI3K/Akt and mTORC1 pathway. It plays an indispensable role in the development of various diseases. However, the relationship between PRAS40 and head and neck squamous cell carcinoma (HNSCC) remains unclear. Here, our study indicated that high expression of PRAS40 mRNA is a favorable prognostic factor in HNSCC patients by analyzing 498 clinical and mRNA data. Moreover, we confirmed that CRISPR/Cas9 induced PRAS40-knockout would promote colony formation, cell migration, and invasion in several HNSCC cell lines. RNA-seq was employed to investigate the further possible mechanisms involving the above regulations by PRAS40 in HNSCC cells. The molecular landscape contributed by 253 differentially expressed mRNA after PRAS40-knockout was enriched in TGF-beta, PI3K-Akt, P53, mTOR, NF-κB signaling pathway. Partial molecular alternations within these pathways were validated by qPCR or Western blotting. Besides, we found that high expression of PRAS40 in HNSC patients would present more CD8+ T and T follicular helper cells, but less Th17 cells than the patients with low expression of PRAS40. The altered molecular pathways and tumor-infiltrating immune cells might associate with the mechanism of PRAS40 being a suppressor in HNSCC cells, which would provide a potential prognostic predictor and therapeutic target in HNSCC patients.


Head & Neck ◽  
2019 ◽  
Vol 41 (5) ◽  
pp. 1199-1205
Author(s):  
Dorival Mendes Rodrigues‐Junior ◽  
Soon Sim Tan ◽  
Sai Kiang Lim ◽  
Luciano Souza Viana ◽  
Andre Lopes Carvalho ◽  
...  

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Liyan Chen ◽  
Yang Yang ◽  
Shuangping Liu ◽  
Longzhen Piao ◽  
Yuan Zhang ◽  
...  

Leucine zipper-EF-hand containing transmembrane protein 1 (LETM1) is a mitochondrial inner membrane protein and plays an important role in mitochondrial ATP production and biogenesis. High expression levels of LETM1 have been correlated with numerous human malignancies. This study explored the clinicopathological significance of LETM1 expression as a prognostic determinant in head and neck squamous cell carcinoma (HNSCC). HNSCC samples from 176 patients were selected for immunohistochemical staining of LETM1 protein. Correlations between LETM1 overexpression and clinicopathological features of HNSCC were evaluated by Chi-squared tests and Fisher’s exact tests, and relationships between prognostic factors and patient survival were analyzed using Cox proportional hazards models. Our results demonstrated that the strongly positive rate of LETM1 protein was 65.3% in HNSCC, which was significantly higher than in either adjacent nontumor tissue (25.0%) or normal squamous epithelia (6.7%). LETM1 overexpression correlated with poor differentiation, presence of lymph node metastasis, advanced stage, absence of chemoradiotherapy, and 5-year disease-free survival and overall survival rates in HNSCC. Further analysis showed that high LETM1 expression, advanced stage, and nonchemoradiotherapy were significant independent risk factors for mortality in HNSCC. In conclusion, LETM1 plays an important role in the progression of HNSCC and is an independent poor prognostic factor for HNSCC.


2019 ◽  
Vol 121 (11) ◽  
pp. 897-903 ◽  
Author(s):  
Thomas H. Beckham ◽  
Jonathan E. Leeman ◽  
Peng Xie ◽  
Xiaolin Li ◽  
Debra A. Goldman ◽  
...  

Abstract Background Our objective was to evaluate the outcomes of metastatic head and neck squamous cell carcinoma (HNSCC) by disease burden with an emphasis on metastasis-directed therapy (MDT) in patients with limited metastatic disease burden. Methods In total, 186 patients who developed metastatic disease after definitive therapy for HNSCC were included. Clinically and radiographically apparent metastases were enumerated. Kaplan–Meier methods were used to estimate survival. Cox regression was used to assess the association between clinical variables. Results Patients with a single metastasis had a 5-year overall survival (OS) of 35% (95% CI 16–54%) in contrast to patients with multiple metastases with a 5-year OS of 4% (95% CI 2–9%). Thirty patients (16.1%) underwent MDT. On multivariable analysis, oral cavity or sinonasal primary (HR 2.22 95% CI 1.16–4.25, p = 0.015; HR 4.88, 95% CI 1.10–21.70, p = 0.037, respectively) were associated with higher risk of death, whereas receipt of MDT (HR 0.36, 95% CI 0.17–0.74, p = 0.006) was associated with lower hazard of death. Median subsequent metastasis-free survival and 5-year survival after MDT (n = 30) were estimated at 26.4 months (95% CI: 9.8–54.0) and 31%, (95% CI: 15–48%). Conclusions HNSCC patients with limited metastatic disease may derive significant benefit from MDT. Prospective trials evaluating MDT in HNSCC are warranted.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5590-5590
Author(s):  
Antonio Lopez-Pousa ◽  
Xavier Leon ◽  
Miquel Quer ◽  
Ana Quintana ◽  
Luis Vila ◽  
...  

5590 Background: There are not validated markers of radioresistance in patients with a head and neck squamous cell carcinoma (HNSCC). The objective of our study was to explore the relationship between response to radiotherapy and the expression at transcriptional level of a panel of genes related with the HNSCC carcinogenic process. Methods: The study group was 76 consecutive HNSCC patients treated with radiotherapy (n=51) or chemoradiotherapy (n=25) with curative intention, and a minimum follow-up of three years. Thirty-seven patients were T1-T2 tumors and 16 had an advanced tumor (T3-T4). Biopsy specimens were performed from the primary tumor before treatment and conveniently stored until processing. Expression of genes related with cell cycle (cyclin D1), apoptosis (Bcl-XL), angiogenesis (VEGF), inflammation (IL-8), and tissue invasiveness (MMP-2 and MMP-9) were examined using a RT-PCR method. The continuous value of the mRNA expression level was evaluated with a classification and regression tree (CRT) method, considering the local control of the disease achieved with radiotherapy as the dependent variable. Results: During the follow-up 26 patients (33.8%) had a local failure. The CRT method found a significant relationship between VEGF and MMP-9 expression and local control of the disease. According the expression level of VEGF and MMP-9 the patients were classified in three groups: the A group (n=19) defined by a low expression of VEGF, the B group (n=19) defined by a high expression of VEGF and a low expression of MMP-9 and the C group (n=38) defined by a high expression of both VEGF and MMP-9. The 5-year local recurrence free survival was: A group 94.7% (CI 95%: 84.7-100%), B group 83.3% (CI 95%: 66.1-100%), and C group 37.6% (CI 95%: 21.0-54.2%). There were significant differences in the local control of the disease according to the VEGF and MMP-9 expression values (test log rank, P<0.0001). Conclusions: Expression of VEGF and MMP-9 genes may be a radiosensitivity marker for patients with HNSCC treated with radical intention. We didn’t find prognostic significance for other genes explored.


2000 ◽  
Vol 122 (5) ◽  
pp. 662-666 ◽  
Author(s):  
Robert P. Zitsch ◽  
Daniel W. Todd ◽  
Gregory J. Renner ◽  
Amolak Singh

OBJECTIVES: We sought to determine the feasibility and utility of intraoperative radiolymphoscintigraphy as a screening procedure for the detection of occult metastatic disease in selected cases of head and neck squamous cell carcinoma (HNSCC). METHODS: Patients with accessible primary HNSCC and no evidence of metastatic disease who were already undergoing planned surgical resection of the primary tumor and elective neck dissection met the inclusion criteria. Before resection, a handheld gamma probe was used to find the radiolabeled sentinel lymph node (SLN). The neck specimen was examined ex vivo by using the gamma probe; the SLN or SLNs were dissected free from the specimen and sent separately for histopathologic examination. RESULTS: At least one SLN was identified in all patients enrolled thus far. Four patients had microscopic carcinoma found in the SLN. Two of these had cancer only in the SLN, and two had disease both in the SLN and the remaining specimen. CONCLUSIONS: Intraoperative radiolymphoscintigraphy appears to be a feasible and promising procedure to aid the surgeon in more accurately detecting occult metastatic HNSCC.


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