scholarly journals A Novel Lipid Prognostic Signature of ADCY2, LIPE, and OLR1 in Head and Neck Squamous Cell Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Xiaolei Gao ◽  
Na Zhao ◽  
Liying Dong ◽  
Xuan Zheng ◽  
Yixin Zhang ◽  
...  
Keyword(s):  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Lipid Metabolism ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Metabolic Reprogramming ◽  
Prognostic Signature ◽  
New Findings ◽  
Tp53 Status

Simple SummaryClinically, aberrant lipid metabolism is responsible for overweight and/or obesity. Overweight is considered as an independent factor of cancer risk in 2019. Therefore, lipid metabolic reprogramming is an emerging hallmark of malignancy. It is an urgent need to comprehensively understand the relationship among lipid metabolism and HNSCC and identify a valuable biomarker for predicting prognosis of HNSCC patients. Three new findings were found in this study. Firstly, we identified the lipid-related differentially expressed genes (DEGs) by using the GEO microarrays and TCGA dataset. A novel lipid-related mRNA prognostic signature (LRPS, consisting of ADCY2, LIPE and OLR1) was developed, which could predict the survival and prognosis of HNSCC patients as an independent effective prognostic factor. Secondly, we found that the LRPS could indicate the type of infiltrated immune cells in HNSCC tumor microenvironment. Thirdly, we verified that the LPPS score could interpret the TP53 status of HNSCC. Our new findings indicated that LRPS has a potential to be a promising indicator of overall survival, TP53 status, and immune characteristics in HNSCC, and perhaps can monitor and guide the treatment efficacy and prognosis of HNSCC in the future.BackgroundHead and neck squamous cell carcinoma (HNSCC) is characterized by a high frequency of lymph node metastasis and a high mortality. Lipid metabolic reprogramming is an emerging carcinogen as its role in fulfilling cancer growth and spread. However, little is known about the correlation between lipid metabolism and HNSCC.Materials and MethodsExpressions of lipid-related genes were obtained from the Cancer Genome Atlas (TCGA) and Gene expression Omnibus (GEO) databases for differential and functional analyses. A total number of 498 patients from TCGA with complete information were included to identify a lipid-related prognostic signature (LRPS), based on ADCY2, LIPE, and OLR1, by using univariate and multivariate Cox regression analyses. LRPS-high and LRPS-low groups were accordingly divided to pathway and cell enrichment analyses.ResultsLRS-low patients had a better overall survival and relapse - free survival than LRS-high ones in HNSCC. The LRPS-high group was significantly related to perineural invasion of cancer, cancer-related pathways, high TP53 mutation rate, high proportion of natural killer T cells (NKT), dendritic cells, monocytes, Treg, and M1 and M2 macrophage infiltration in HNSCC tumor tissues. Conversely, the LRPS-low group correlated with DNA damage-related and T-cell-regulated pathways, low frequency of mutated TP53, and high infiltration of B cells and CD4+ effector cells including Th1 and Th2.ConclusionLRPS has a potential to be a promising indicator of overall survival, prognosis, TP53 status, and immune characteristics in HNSCC.

scholarly journals The Prognostic Value and Immune Landscapes of a m6A/m5C/m1A-Related LncRNAs Signature in Head and Neck Squamous Cell Carcinoma

2021 ◽  
Vol 9 ◽  
Author(s):  
Enhao Wang ◽  
Yang Li ◽  
Ruijie Ming ◽  
Jiahui Wei ◽  
Peiyu Du ◽  
...  
Keyword(s):  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
High Risk ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Risk Group ◽  
Prognostic Signature ◽  
Mutational Burden ◽  
Tumor Mutational Burden

Background: N6-methyladenosine (m6A), 5-methylcytosine (m5C) and N1-methyladenosine (m1A) are the main RNA methylation modifications involved in the progression of cancer. However, it is still unclear whether m6A/m5C/m1A-related long non-coding RNAs (lncRNAs) affect the prognosis of head and neck squamous cell carcinoma (HNSCC).Methods: We summarized 52 m6A/m5C/m1A-related genes, downloaded 44 normal samples and 501 HNSCC tumor samples with RNA-seq data and clinical information from The Cancer Genome Atlas (TCGA) database, and then searched for m6A/m5C/m1A-related genes co-expressed lncRNAs. We adopt the least absolute shrinkage and selection operator (LASSO) Cox regression to obtain m6A/m5C/m1A-related lncRNAs to construct a prognostic signature of HNSCC.Results: This prognostic signature is based on six m6A/m5C/m1A-related lncRNAs (AL035587.1, AC009121.3, AF131215.5, FMR1-IT1, AC106820.5, PTOV1-AS2). It was found that the high-risk subgroup has worse overall survival (OS) than the low-risk subgroup. Moreover, the results showed that most immune checkpoint genes were significantly different between the two risk groups (p < 0.05). Immunity microenvironment analysis showed that the contents of NK cell resting, macrophages M2, and neutrophils in samples of low-risk group were significantly lower than those of high-risk group (p < 0.05), while the contents of B cells navie, plasma cells, and T cells regulatory (Tregs) were on the contrary (p < 0.05). In addition, patients with high tumor mutational burden (TMB) had the worse overall survival than those with low tumor mutational burden.Conclusion: Our study elucidated how m6A/m5C/m1A-related lncRNAs are related to the prognosis, immune microenvironment, and TMB of HNSCC. In the future, these m6A/m5C/m1A-related lncRNAs may become a new choice for immunotherapy of HNSCC.

scholarly journals Cigarette Smoke Induces Metabolic Reprogramming of the Tumor Stroma in Head and Neck Squamous Cell Carcinoma

2019 ◽  
Vol 17 (9) ◽  
pp. 1893-1909 ◽  
Author(s):  
Marina Domingo-Vidal ◽  
Diana Whitaker-Menezes ◽  
Cristina Martos-Rus ◽  
Patrick Tassone ◽  
Christopher M. Snyder ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Cigarette Smoke ◽  
Squamous Cell ◽  
Tumor Stroma ◽  
Metabolic Reprogramming ◽  
Neck Squamous Cell Carcinoma

scholarly journals Expression of the Extracellular Sulfatase SULF2 Affects Survival of Head and Neck Squamous Cell Carcinoma Patients

2021 ◽  
Vol 10 ◽  
Author(s):  
Yang Yang ◽  
Jaeil Ahn ◽  
Rekha Raghunathan ◽  
Bhaskar V. Kallakury ◽  
Bruce Davidson ◽  
...  
Keyword(s):  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Hpv Infection ◽  
Neck Squamous Cell Carcinoma ◽  
Therapeutic Interventions ◽  
Tumor Tissues ◽  
Significant Difference

Sulfation of heparan sulfate proteoglycans (HSPG) regulates signaling of growth factor receptors via specific interactions with the sulfate groups. 6-O-Sulfation of HSPG is an impactful modification regulated by the activities of dedicated extracellular endosulfatases. Specifically, extracellular sulfatase Sulf-2 (SULF2) removes 6-O-sulfate from HS chains, modulates affinity of carrier HSPG to their ligands, and thereby influences activity of the downstream signaling pathway. In this study, we explored the effect of SULF2 expression on HSPG sulfation and its relationship to clinical outcomes of patients with head and neck squamous cell carcinoma (HNSCC). We found a significant overexpression of SULF2 in HNSCC tumor tissues which differs by tumor location and etiology. Expression of SULF2 mRNA in tumors associated with human papillomavirus (HPV) infection was two-fold lower than in tumors associated with a history of tobacco and alcohol consumption. High SULF2 mRNA expression is significantly correlated with poor progression-free interval and overall survival of patients (n = 499). Among all HS-related enzymes, SULF2 expression had the highest hazard ratio in overall survival after adjusting for clinical characteristics. SULF2 protein expression (n = 124), determined by immunohistochemical analysis, showed a similar trend. The content of 6-O-sulfated HSPG, measured by staining with the HS3A8 antibody, was higher in adjacent mucosa compared to tumor tissue but revealed no difference based on SULF2 staining. LC-MS/MS analysis showed low abundance of N-sulfation and O-sulfation in HS but no significant difference between SULF2-positive and SULF2-negative tumors. Levels of enzymes modifying 6-O-sulfation, measured by RT-qPCR in HNSCC tumor tissues, suggest that HSPG sulfation is carried out by the co-regulated activities of multiple genes. Imbalance of the HS modifying enzymes in HNSCC tumors modifies the overall sulfation pattern, but the alteration of 6-O-sulfate is likely non-uniform and occurs in specific domains of the HS chains. These findings demonstrate that SULF2 expression correlates with survival of HNSCC patients and could potentially serve as a prognostic factor or target of therapeutic interventions.

Survival results of phase I dose escalation of stereotactic body radiation therapy and concurrent cisplatin for re-irradiation of unresectable, recurrent head and neck squamous cell carcinoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18020-e18020
Author(s):  
Michelle Echevarria ◽  
Christine H. Chung ◽  
Kedar Kirtane ◽  
Jameel Muzaffar ◽  
Julie Ann Kish ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Radiation Therapy ◽  
Phase I ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Stereotactic Body Radiation Therapy ◽  
Recurrent Head

e18020 Background: Stereotactic body radiation therapy (SBRT) is a standard option for re-irradiation of recurrent or second primary cancers of the head and neck. We conducted performed a phase I clinical trial to establish a maximum tolerated dose of SBRT with concurrent cisplatin. We previously reported our safety data, and now present our secondary disease control endpoints. Methods: Major inclusion criteria were recurrence of previous squamous cell carcinoma of the head and neck in patients who had previously undergone radiotherapy to doses ≥ 45 Gy to the area of recurrence, ≥ 6 months prior to enrollment, and who were medically unfit for surgery, deemed unresectable, or refused surgery. Patients were treated with radiation therapy every other day for five fractions at three dose levels: 30 Gy, 35 Gy, and 40 Gy. Cisplatin was given prior to every SBRT fraction at a dose of 15 mg/m2. Secondary end points reported herein are locoregional control (LRC), freedom from distant metastasis (FFDM), and overall survival (OS). Results: Twenty patients were enrolled and of those 18 patients were evaluable for secondary endpoints. Nine patients had a primary tumor in the oropharynx, four patients in the oral cavity, three in the neck, one in the larynx, and one simultaneously in the larynx and neck. All patients received the planned dose of Cisplatin. Five patients received a radiation dose of 30 Gy, three patients received a dose of 35 Gy, and 9 patients received a dose of 40 Gy. Median gross tumor volume (GTV) was 11.725 cm3. With a median follow up of 9 months the 1-year OS was 38.9%. LRC at 1 year was 45.7% and FFDM at 1 year was 87.8%. There was a trend to improved OS with increasing SBRT dose, 40 Gy vs < 40 Gy (p = 0.08). There was an improved 1-year OS with a GTV ≤11.725 cm3 of 77.8% vs 0% for tumors > 11.725 cm3 (p < 0.001). For patients with a GTV < 11.725 cm3 who received 40 Gy the 1 year OS was 100% compared with 0% for tumors larger than 11.725 cm3. Conclusions: For patients with previously radiated locally or regionally recurrent head and neck cancer, SBRT up to 40 Gy given concurrently with cisplatin provides reasonable locoregional control and overall survival for patients with smaller tumors. Further evaluation in prospective trials is warranted. Clinical trial information: NCT02158234.

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