Tumor microenvironment and immune-related therapies of head and neck squamous cell carcinoma

Cao

et al. 2021

neo

This study aims to elucidate the potential genes of the matrix metalloproteinase (MMP) family, responsible for the progression of laryngeal squamous cell carcinoma (LSCC). Besides, we ascertained the changes in common malignant behaviors in vitro by knocking down MMP1. TCGA, GEO, Oncomine, and Microarray data were conducted to analyze the expression levels of MMPs and to find tissue-specific genes in LSCC. Univariate and multivariate Cox regression analyses were established in the construction of a prognostic model based on expression profiles and clinical information of LSCC in TCGA. We then comprehensively analyzed survival, co-expression network, and immune infiltration based on a prognostic model by Kaplan-Meier analysis, WGCNA, and CIBERSORT. Thereafter, qRT-PCR, proliferation, Transwell, and wound healing assays were used to assess the accuracy of the bioinformatics data. A total of seven genes in the MMP family were identified as differentially expressed genes (DEGs) by integrating three public databases and microarray data. Additionally, multivariate Cox regression was used to establish a four-gene (MMP1/3/8/10) prognostic model, which exhibited a better predictive accuracy than the TNM (tumors/nodes/metastases) based model. The prognostic model was related to plasma cells, CD8+ T cells, follicular helper T cells, resting NK cells, and M0 macrophages infiltration. The expression of MMP1, MMP3, and MMP10 was the highest in head and neck squamous cell carcinoma (HNSC) compared to other cancer in the Oncomine and GEPIA dataset. Further, MMP1 demonstrated significant upregulation in 40 paired LSCC tissues. Eventually, MMP1 downregulation inhibited cell viability, colony formation, and cell migration in TU686 and FaDu cells. Our findings suggest that the four-gene signature might be associated with the prognos is. Further, we revealed that MMP1 is a pivotal biomarker for the biotherapy and prognostic evaluation of patients with LSCC.

Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 69%

Section: Discussionmentioning

confidence: 99%

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The matrix metalloproteinase gene family: a significant prognostic gene lineage correlated with immune infiltrates in laryngeal squamous cell carcinoma

Cao

et al. 2021

neo

“…Head and neck squamous cell carcinoma (HNSCC) represents the sixth most common malignant tumor in the world ( Johnson et al, 2020 ). These tumors originate from the mucosa of various anatomical parts of the oral cavity, pharynx, larynx and sinonasal tract and are heterogeneous in etiology and clinicopathological characteristics, and these highly aggressive malignant tumors affect more than 830,000 patients worldwide each year ( Johnson et al, 2020 ; Qin et al, 2021 ). HNSCC is usually associated with exposure to tobacco-derived carcinogens, excessive alcohol consumption, or both.…”

Section: Introductionmentioning

confidence: 99%

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

Wang

Ming

et al. 2021

Front. Cell Dev. Biol.

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.

“…The immune cells in TME can affect patients' survival [ 25 ]. To explore the mechanism of FH affecting patients' prognosis, the correlation between FH expression and immune infiltration in pan-cancer was further investigated.…”

Section: Resultsmentioning

confidence: 99%

Pan-Cancer Analysis Reveals FH as a Potential Prognostic and Immunological Biomarker in Lung Adenocarcinoma

Zhang

et al. 2021

Disease Markers

Fumarate hydratase (FH) is an important enzymatic component in the tricarboxylic acid cycle. Studies have reported that FH plays an important role in hereditary leiomyomatosis and renal cell cancer (HLRCC). However, the role of FH in human different cancers remains unknown. This study is aimed at analyzing the prognostic value of FH and demonstrating the correlation between FH expression and tumor immunity. Results showed that FH was mutated or copy number varied in 27 types of cancer. FH mRNA was abnormally upregulated across various cancers. Survival analysis suggested high expression of FH was associated with poor prognosis in many cancer types, including lung adenocarcinoma (LUAD). Additionally, FH expression was associated with immune infiltration, including B cells, CD4+ T cells, CD8+ T cells, neutrophils, macrophages, and dendritic cells, especially in liver hepatocellular carcinoma (LIHC), LUAD, and lung squamous cell carcinoma (LUSC). Moreover, FH expression showed a strong correlation with immune checkpoint markers in LUAD and testicular germ cell tumors (TGCT). These results indicate that FH is an immunotherapeutic target and a potential prognostic biomarker in LUAD.